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Robbins

Review

01

PATHOLOGY Edward C. Klatt, M.D. Professor of Pathology

1ñe UnivcrsilY of Utah Health Sciences Center Sall Lake CiIY, Utah

Vinay Kumar, M.D., F.R.C.Path. VLTnic A. Stcmbridge Chair in F-dthology Department of Pathology The University of Texas Southweslem Medica! School Dalias, Texas

W.B. SAUNDERS COMPANV A HoT'OOflt't HtDltlt Scknc~s Company Philadtlphia London New Yori: St.louís

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W.H. SAUNDt:RS COi\lI'Al\"Y lo Har«JVr1 HtoltJt SdOIU.f Com¡KJny

Thl: Curtis Cenia' lndepcndaJa: Square Wc:st: Ptliladdphia, PmIli)'I~'lIllia 19106

Ubnlry 01 Congreaa Catatoglng-ln-PUbliClllion Data Klall. Edward C. Aol;ltWls revIew 01

~IEOOard

C. Klall. Vnly Kumar-lst OO,

ISBN 0-1'216-8259-6

l. PIIIhoIogy-Exai........... quesli(IIW. etc. L 1llIB; Fleview el pehdollY. 11. RdIbins, Slariey L (Sl8Aey Leonard) lit Kunur, VII'IIIy. IV. nle. DI'I-M: 1. f'IlItJok)¡w.

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2000l RB119.K562000

ACqtlisitions &filar.

99-057050

616.07'076-dc:21

William Sduniu

Hazel Hackc:r Proj«I Manogtr. Agna Hunt B)mt Produc/imJ Morwgtr. Petl:: Faber IlIU.f1rotion Sp«ioIur; Pe!; Shaw Bcok Dtsigntr. hui Fry 1Ñ\"t/opnIDlIof Editor.

ROBBINS REVIEW 01' PATHOLOGY

ISBN o-nI6-82.59-6

OJp)Tigtu. O 2000 W.B. Saunders Complllly. A11 righls 1l'2n'ed. No pal1 of Ihis PJbliaJlion may be reproclua:d or lnansmillcd in "'y forrn 01" by illl)' mearos. decIronic or medIanil:al, induding phouJalpy. reoording, or any infonnation Wll"3ge and rttriCial. 5)"Qem, ....ithDut ~ in ""Tiling fl'lll'lllhe pablilJltt.

Priltlcd in l1E Unitcd SUlles of Amcrica.

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Preface This book is designcd lO provide a comprchc~ive review of palhology lhrough multiple choice queslions aod explanalions of the answen隆, The source malerials are the sixlh editions of Cotrno. Kumar. Collins: Robbins PalllOJogic Basis of Disease (PB06) and Kumar. Cotran. Robbins: Bo.sic PlIlhoJogy (BP6). 11 is iotended. to be a useful rcSQurce for studenls at a var;ety of lcvcls, including Ihose io the allicd hcallh profcssioos. lo kccpiog wilh thc slyle uscd by the USMLE, anly twa queslion formats are uscd: siogle besl answcr and extended malching. The majority of the qucstians cenlain a c1inical vignctlc that is followOO by a series of homogcnous, choiccs. This approach cmpbasizes an undcrslanding of mcehanisms and manifcstations af discasc in a c1inical, conlexl Wht:rever possiblc. wc havc incorporatcd rclcvant Iab-oratory. radiologic. aod physical diagnostic findings in thc q1JCStions lO emphasize c1inicopathologic correlalions. For cach qocslion, thc correct answcr is providcd with a bricf cxplanalion of why thc corrcct answer is "correet" and why the Olhcr choiccs are "incorrccl." Each answcr is rcfcrenced

lO Robbins Po.tllologic Basis of Diseas~ and 10 Basic Po.路 thology to facililale and cncourage a more complete reading of thc tapie. Palhology is a visuaUy orienled discipline and hcncc we havc used fuI! celor images in many of the qucslions. Thc iUustrnlions are takcn from the Robbins tcxlbooks. so sludcnts can rcinforce thcir sludy of the iIIustralions in the lext with qucstions thal ulilize thc samc images. Thc qucstions are inlcntionally fairly difficult. with the purpose of "pushing Ihe envelopc" of student undcl'}llanding of pathology. We hope, thercfore, that this texl will be oseful nol only prior 10 cxaminalions bUI aJso during the course. We must haslcn lO add thal no rcview book is a Subslitule for thc textbooks and olhcr course material providcd by individual inslructors. The bcst use of this book wiU be after a tIx>rough Sludy of Robbins PatllOJogic &su of Visease and/or Basic PathoJog)'. Finally. we hape that sludctlls and instructors will find this review book lO be a uscful adjunct lO thc lcaming of palhology.

EDWARD C. KLArr VINAY KUMAR

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i Acknowledgments We are vcry gralcful lo OUT cdilorial assistlmlS, Bevcrly Shackclford lmd Carolyn Ostcrman, for thcir invaluablc hclp in Ihe production of the numuscripl. Thanks are also duc lo Hazel Hackcr, OUT Ocvelopmcntal Editor. and William Schmill. Editor-in-et煤cf. ML-dical Books. W.B. Saun-

dcrs Company, for their support of Ihis projoct. Lasl bul nol leasl, wc are grateful lo OUT familics and collcagucs for graciously acccpting Ihis additional dcmand on OUT ,ime, EDWARD C. K1.Arr VINAY KUMAR

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Contents PART 1 GENERAL PATHOLOGV

1. Ce1Jular Pathology

14. Whne Cel~. Lymph Nades. Spleen. and Thymus ,

'

15. The Lung 2. Acute and Chronic Inflammotlon

, .•••.......... 153

, .. 11

3. Tissue Repoir: Cenular Growth. Rbrosis. and Wound Healing

1B

4. Hernodynamie Disorders. ltvombosis. and Shock

21

5.

Genetle DisordefS

29

6. [)Iseoses of IllVT)unity

36

16. Head and Neck

168

17. The Gostrointeslinallract

173

11. The Uver and the BiliOly Traet

190

19. The Poncreos ." _ 20.

7. NeopIasia

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8. Infectious Dlseases .. ,

136

3

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9. Envlronmental and Nutritional Pathology

,

The Kidney and the LOINer Urinary Troct , , .. ,

, 203

210

51

21. The Male Genital Troct.

229

64

22. The Female Genital Tract .. ,

236

78

23. The Breast

249

1O. Dlseoses of Infancy and Chlldhood . , . .. . .. 89

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24. The Endocrlne System 25.

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The Skin

267

PART 2

26. Banas. Joints. and 50ft rlSSue Tumors

274

101

27. Peripheral Nerve and Skeletal MuscIe

286

11 O

28. The Central Nervous System

290

123

29.

DISEASES Of ORGAN svmMS

11. B100d

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12. The Heart 13.

Red

cells and 8leeding DisordefS

The Eye

305

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PAR T

GENERAL PATHOLOGY


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CHAPTER

1 Cellular Pathology PBD6 COOpter 1 - Cellular Pathalagy I PBD6 COOpter 2 - Cellular Pa1halagy 11 8P6 COOpter 1 - Cell Injury. Death. 000 Adaptotion

1. A 17-ycar-old male infcetcd with hepatitis A experiencc.o; somc mild nausea for aboul a wcek and ha<; very mild sclcral icleros. LaboralOf)' findings ¡nelude c1evations in the leve1s of the hcpalic cnzymcs aspartalC lransaminase (AS1) and a1anine transaminasc (ALT). The incrcase in lhe enzymc levels in the serum rcsults froro which of Ihe following changcs in the hepalocytcs?

O (A) Dispersion of ribosomes 0(8) AUlophagy by lysosomes O (C) Swelling of the mitochondria

0(0) Oumping of nuclear chromalin O (E) Dcfccls in Ihe cell mcmbrclllc

2. A 54-year-old male expcrienccd !he onsel of severe chest pain. An e1cctrocardiogram demonstmtcd changcs consistenl with an acule myocardial infarction. He wa.. given Ihrombolytic ther<lpy wilh tissue plao;minogen aclívalor (tPA). However, his serum crealine kinase incrca..cd arler this therapy. Which of tbe following evems mosl likely occurrcd?

O (A) Repcrfusion injury 0(8) O (C) O (O) O (E)

Cellular rcgencralion Chcmical injury Incrcascd synthcsis of crcatine kinase Myofibcr alrophy

3.

A 51-year-old male hao; a blood prcssure of 15QI95 mm Hg. If this condition rcmains unlrcalcd fOl" years. which of thc following cellular ailcrations will be sccn in thc heart?

O(A) Atrophy 0(8) Hypcrplasia O (C) Metaplasia O (O) Hemosidcrosis O (El lIypcrtrophy

4. The aonic valvc secn in the figure was discovercd at the aulopsy of a 72-year-old male. The heart weighcd 580 g, with markcd len ventricular hypcnrophy and minimal eoronary arterial alherosclerosis. A serum chcmistry panel rcvcalcd no abnonnalilics prior lO dcath from congestivc hean failure. Which of the following palhologic proccsscs accounts for Ihe appcarancc of the valvc?

o (A) O (B) O (C) 0(0) O (E)

Amyloídosis Oystrophic calcificalíon Lipofuscín dcposítion Hcmosidcrosis Fally change

5. A righl carotid cndanctcetomy is pcrformcd on a ff)year-old female who had an audible bruil on auscu1talioo of the ncck. Examinalion of Ihe curettcd alhcromalous plaque rcvcals a grossly ycllow-Ian, finn appcarancc. Microscopically. which of lhe following malcrials can be found in abundance in lhe foon of crystals producing long, c1eftlike spaces?

O (A) Glycogen 0(8) Lipofuscin

O (Q Hcmosidcrin O (O) lmmunoglobulin O (El Cholcstcrol 3.


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GENERAL PATHOLOGY

change results from which of Ihe fol1owing altcrations in lhe calf musclcs" OCA) 0(8) O (C) O (O) O (E)

Aplasia Hypoplasia Atrophy Oyslrophy Hyalin ehangc

11. Whieh of the following cclls have the higbest Iclomerase aetivity? Endothclial cclb Gcnn cclls Ncurons Nculrophils O (E) Erylhrocytes

O (A) 0(8) O (Q 0(0) 6. A 38-ycar-cld woman expcricnced severc abdominal pain with hypOlension and shock lhal loo 10 hcr dcath within 36 hOllrs. From the gross appcarance of IOC rocscn-Icr:y. sccn in Ihe figure. which of lhe foJlowing cvcnts has most likely occurrcd? oCA) O(B) O (C) O (O) O (E)

Hepatitis B virus ¡nfcction Small inteslinal infan:lion Tubcrculous Iymphadcnitis Gangrcnous eholecystilis Acute pancrealitis

7. Absorptlon of radianl cncrgy. such as x-rnys. can resull in cell injury by causing hydrolysis of WalCf. Which of lhe fol1owing celluJar cnzymcs proU.'ClS cclls from Ihis Iype of injury? OCA) Phospholipasc O (B) Glulalhione pcroxidasc O (e) Endonuclcasc 0(0) Lactate dehydrogcnase O (E) Protca<>es 8. In palients with emphysema due lO o.-anlilrypsin dcfidency. the molecular lTIeehanism rcsponsible for Ihe accumuJation of O'I-élnlitrypsin in hcpalocylcs is OCA) Excessive hcpalic synlhcsis of O',-anlitrypsin O(B) Retcntion in Ihe endoplasmic reliculum bccause of poorly foldcd O',-anlitrypsin O(e) Dccrca.~cd calabolism of O',-anlitrypsin in Iysosomes OíD) lnabilily lO mClaboli....c O'I-anlilrypsin O (E) Impairc<l dissocialion from chaperones

9.

A 63-year-old man expcricnccd diaphoresis and subslcmal chest pain aflcr thrombosis of Ihc left anlerior desccnding artcry. His scrum Crcal.ine kinase lcvcl was ele-valed. Which of lhe following paltems of Iissue injuey wa.c; most likcly?

OCA) O (8) O (C) 0(0) O (E)

Liquefaetive necrosis necrosis Coagulalive necrosis P<l.1 necrosis Gangrenous necrosis Cascou~

10. Aftcr scvcral wccks of immobilization of the Icg in a plastcr casl, lhe diamctcr of loc calf orten dccreascs. This

12. A 32-year-old mate expcriences "heartbum" wilh substemal pain from reflux of gastrie contcnts ¡nlO lhe lower esop'hagus. After many lnonlhs. lhe csophagcal epithc1ium exhibils lhe microscopic appearancc shown here. Which of Ihe following palhologic altc('dlions has oceurrcd'! OCA) O(B) O (e) O (O) O (E)

Squamous mClaplasia Mucosal hypcrlrophy Columnar epilhclial metaplasia Alrophy of lamina propria Goblet ccll hypcrpla...ia

13. On day 28 of lhe mcnslrual cycle in a 23-year-old female,. Ihere is menslrual blcerling lhal lasts for a fcw days. She has had thesc regular cycles for many ycars. Which of lhe following proccsscs is mosl likely happening in loc cndometrium jusI bcforc lhe onsct of blceding? O(A) Apoplosis 0(8) Cascoos necrosis O (q Iletcrophagocylosis 0(0) Atrophy O (E) Liquefaetivc necrosis 14. Many drugs lhat are uscd to {real cancer cause dcalh of tumor cclls by apoplosis. Mutarional inactivation of which of the fol1owing genes can rcnder tumor cclls resislanl lO thc effocts of such chcmolhernpcutie drugs?


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O(A) bcl-2 O(B) p53

0(0 NF-K8 0(0) P450 O (E) Granzymc 8

15. After me binh of hcr first child, a 19-ycar-old femalc bcgan breast-fceding the baby. She continucd breast~fecd­ ing for almost ayear. Which of the following processcs that occurrod in the brcast during prcgnancy allowcd hcr lO nurse !he infam? O(A) Stromal hypcrtrophy

CELlULAR PATHOLOGY

5

palpably enlargcd to abaut twicc normal size. A trnnslU"e'thral rcscclioo of the prostate is pcrformcd, and the microscopic appcarance of the prostate "chips" obtaincd is that of nodules of glands with intcrvcning stroma. ( ) 19. Blunt lrnuma lo lhe abdomen of a l6-year-old male occurred during a vcrncular accident in which he lost control of the vchiclc al high spccd aod struck a bridge abutmcnl He is found tO have a hemopcritoncum, and at laparotomy, a small portion of thc Icn 1000 of the liver was rcscctcd bccausc of the injury. Wecks Iater, !he liver had rcgaíncd its normal size. ( )

0(8) Lobular hypcrplasia

O (C) Epithclial dysplasia O(D) Intraccllular accumulatíoo of fal O (E) Ductal epithelial metaptasia

16. A 22-year-old fcmale has a congenilal anemia !hal rcquired mulliple transfusions of red blood cells for many ycars. Shc now has no significant findings on physical examination. However. her liver functíon test resulto¡ are abnormal. Which of the following findings would most Iikcly appcar in a livCT biopsy? O(A) Stcatosis in hepatocytes O (B) Bilimbin in canaliculi O (Q Glyoogcn in hepatocytes 0(0) Amyloid in portal triads O (E) Hemosidcrin in ocpatocytes For caeh of lhe c1inical histories in queslions 17. 18. and 19, match the most c10sely associaled letlcred dcscription of a form of cellular change or injury: (A) Apoptosis (8) Atrophy (C) Cascous necrosis (D) Coagulative necrosis CE) Dysplasia (F) Dyslrophic calcificalion (G) Fal necrosis (H) FallY change (1) Gangrcnous necrosis (J) Hydropic change (K) Hypcrplasía (L) Hypcnrophy (M) Liquefaetive necrosis (N) Metaplasia (O) Metaslatic calcitication 17. A 3-cm,. right middie lobe lung nodule was secn on a chest radiogrnph of an a<;ymptomatic 37-year-old male. lbe nadule was exciscd with a pulmonary wedge resection by the thorncic surgcon. On scctioning by the pathologist, the nadule was sharply cifCUmscribcd and had a 50ft. white center. Cvlturc of lissue from lhe nodule grcw M)'cobaclerium luberculosis. ( )

18. A 69-year-old male has difficulty with urinarian. A digital rectal eX1l.minalion revcals that the proslalc gland is

20. Accumulation of Iipofuscin granulc... in cells is typically secn in which of the following conditions? OCA) O(B) O (e) O(D) O (E)

Alrophy Hypcnrophy Hypcrplasia Melaplasia Apoplosis

21. A 40-year-old ma.lc was diagnosl..'(j Wilh an uodiffercntiatcd carcinoma of Ihe lung. Dcspilc lreatmcnt with chcmothcrapy, he dicd of widc:sprcad mctastases. Al autopsy, tumor was found in many organs. Hislologic examinalion rcvealcd many foci in which individual tumor ceUs appcarcd shmnken and dccply cosinophilic. 1beir nuclci showcd coodcnscd aggregatcs of chromatin undcr !he nuclear membrane. lbe proccss affccting thcse shrunken tumor cells \VaS triggcred by !he rclcasc of which of the following prOleins imo the cylosol? OCA) Lipofuscin Cytochrome c Catalase

0(8) O (C) O (O) O (E)

Pho<phol;pare bcl-2

22. Mcta..talic calcification is mast likc!y lO occur in which of the following condilions? O(A) O (B) O (C) O(D) O (E)

Tuberculosis of the lung Acule hcmonhagic pancrcatilis Aortic stenosis in a 70-year-old man Vitamin D intoxication Arnyloidosis

23. A 68-year-old fcma1c suddcnly losl consciousness ando on awakcning an hOlJr later, coold not speak or move hcr righl ano and leg. Two months later, a head computcd lOmogmphy (CI) sean showed a large cystic arca in her left parietal lobe. Which of the following pathologic proccsses masl likely occurred in lhe brain? O(A) Fat necrosis 0(8) Coagulative necrosis

O (q Apoptosis O (D) Liquefaetivc necrosis O (E) Karyolysis


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GENERAL PATHOLOGY

O (A) AClivation of caspascs O(B) Reduced ATP synlhcsis O (C) Inerca~ glycolysis 0(0) Activation of lipases O (E) Lipid pcroxidation 26. At aulopsy. Ihe heart of a 63-year-old male is only 250 g. with small righl and Icfl vemriclcs. The myocardium is firmo wilh a dark chocolate brown color throughoul. The coronary arteries demonstrale very liltle atherosclcrosis. Which of lhe following substances will moSI ükely be found in lhe myocardial fibers of Ihis heart?

Court~y uf Dr. Jame~ Q-awford. Ocp¡tJ1ment of Pathology. Brigham and Womcn's Hospital, Boston.

24. Al autopsy, a 40-year-old male has an enlarged (2200 g) liver with a yellow cul surface. The microscopic appcarance of this liver is shown in Ihe figure. Before dealh. rus tOlal scrum cholcsterol and triglyceride lcvels wcre normal. bul he had a dccrea~ scrum albumin concentration and increascd prolhrombin lime. Which of lhe following activilics by lrus man most likely Icd lo Ihese findings? O(A) O (B) O (C) O (O) O (E)

Injccling heroin Playing baskelball Drinking hecr Smoking Ingesling aspirin

O(A) O (B) O (C) O (O) O (E)

Melanin Hemosiderin Glycogen Lipofuscin Bilimbin

27. A pneumoncetomy is pcrforrned for lung cancer diagnoscd in a 69-year-old female. Exarnination of Ihe hilar Iymph nades reveals a unifonn dark black cul surfacc. What is most likely to account for Ihis appearance of these Iymph nodes? O(A) O (B) O (C) O(D) O (E)

Smoking A blccding disorder Liver failure Aging Melaslascs

28. Dcposition of calcium in the renal tubular epilhclium in palienls wilh primary hypcrparathyroidism is Ihe resuh of which of lhe following proccsscs? O(A) O (B) O (C) O(D) O (E)

Oyslrophic calcification Renal lubular atrophy AUlophagocylosis Metastatic calcificalion Cellular aging

29. A renal biopsy is pcrformed on a 33-year-old female who has had incrcasing renal failure for the paSI week. Which of the following changcs sccn with electron microscopy most likcly suggcsts a diagnosis of acute tubular necrosis? O(A) O (B) O (C) O (O) O (E)

Milochondrial swelling Plasma membmne blebs Chromatin dumping Nuclear fmgmcmalion Ribosomal disaggregation from endoplasmic reliculum

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25. The cellular change in lhe epidermal cell located in lhe midepidcnnis. in the figure. rcsults from which of lhe following biochemical reactions?

30. Reperfusion of ischemic lissues. as may occur after therapcutic use of Ihrombolylic agents. somelimes leads to ccll dcath after the blood flow resumes. The biochemical basis for ccll dealh undcr thesc cireumstances is most likely which of lhe following? O(A) Reduclion in prolCin synthesis O (B) Increascd generalion of oxygen-derived free radicals


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CEllULAI( PATHOlOGY

7

Incrcascd aetivity of catala.sc 0(0) Rcduccd oxidalive phosphorylalion O (E) Relea.<;e of calcium from endoplasmic reliculum

rcgeneralion or atrophy. The IPA docs nol produce a chemical injury hui induces thrombolysis lo restore blood f1ow.

31. A 50-year-old maJe experienccd sc\·cral episodes of chest pain befare his death. A histologic scclion of left venlricular myocardium taken al aulopsy showcd a dceply cosinophilic staining arca with loss of nuclei and cross· striatioos in myocardial fibers. Thcre was no hemorrllage ( r inflammalion. Which of lhe following condilioos most likely produced thcse myocardial changes?

3. (E) Thc pressure load on the left vet1lricle results in an increase in myofilaments in lhe existing myofibers. The resull of continued stress fmm hypcrtension is evcntual hcart failure with dccrca.'>Cd conlractilily. hut the cells do not decrcasc in sizc. Metaplasia of musclc d0C5 nol occur, allhOllgh loss of muscle occurs wilb aging, with replacemcnt by fibrous tissuc and adipose tissue. Hemosiderin deposilion in heart is a pathologic process resulling from incrcascd iron slores in lhe body.

OCA) Viral infcelion O (B) O (C) 0(0) O (E)

Coronary artcey thrombosis Blunt chesl trauma Anlibod.ies dircctoo against myocardium A prolein-deficient diet

32. The nonpregnanl uteros of a 20-year-old femaJe rneasurcd 7 X 4 X 3 cm. She becallle pregnanl, and jusI before dcli\'ery of a lerm infant. Ihe uterus measurcd 34 X 18 X 12 cm. Which of the following cellular processcs was the major rcason foc Ihe incrca'>C in the size of the uteros? O (A) Endomctrial glandular hypcrplasia O (B) Myomclrial fibroblast proliferation O (C) Endomctrial slromal hypcrtrophy O (O) Myomclrial smooth muscle hypertroJity

O (E) Vascular endothelial hyperplasia 33. A 40-year-old female with chronic congcstive heart failure has a rough productive of ruSl-colorcd spulum. A sputum c)'1ology spccimcn shows numcrous hemosiderin· laden macrophagcs. Which of the following subcellular Slructures in macmphages is most importanl for lhe accumulation of Ihis pigment?

OCA) Lysosomc O (B) Endoplasmic reliculum O (C) Ribosome O (D) Golgi apparalUs O (E) Chromosome

ANSWERS l. (E) Irrevenlible cell IflJury is associalcd with loss of mcmbrdne inlegrity. This allows intraccllular enzymcs to leak into the scrum. AlI othcr morphologic changes Iisted are associaled with reversible cell injury, in which the cell mcmbrane remains intact.

BP66-8 PBD6 7-9 2. (A) The resloralion of blood f10w is helpful if the exiSling cell damage is not greal. and furthcr damage can be prcvented. However, thc rcperfusion of damagcd cclls rcsults in generalion of oxygen-derived free radical s lo produce a repcrfusion ¡njuey. The c1cvaljon in lhe creatine kina'>C level is indicative of myocardial cell ncem"is, not

BP69-10 PBD6 12-13

BP622 PBD633-35 4. (8)·me valve is stcnolic bccausc of nadular deposits of calcium. The proccss is "dyslrophic" bccause calcium dcpositioll occurs in damaged tiSSllCS. The damagc here results from wear and tear of aging. Amyloid dcpositioll in lhe heart typically occurs wilhin !he myocardium and the vessels. The amount of Iipofuscin increascs within myocardium with aging. With a genclic defecl in imn absorption known as hercditary hemochromalosis, there is extcnsivc myocardial imn dcposition. Fatly change is uncornmonly sccn in myocardium. bUI infilml.tion of fal cells can QCCur.

BP620 PBD643-44 5. (E) Cholesterol is a forro of lipid comlllonly depositcd within atheromas in arterial walls, imparting a yellow color lO Ihese p1aque.... Glycogcn is a S10rage form of carbohydrate secn mainly in liver and muscle. Lipofuscin is a brown pigmcnl that increases with aging in celJ eytoplasm. mainly in cardiac lIl}'ocytes and in hepa1ocytes. Hcmosidcrin is a storage forro of imn lhal appcaTS in lissues of thc Illonoouclear phagocyte system (e.g.. marrow. liver. splcen) bul can be widcly depositcd wilh hcrcditary hcmochmmatosis. lmmunoglobulin occasionally may be seco as roundcd globulcs in plasma cells (Le., Russcll bodics,.

BP6 18 PBD6 40 (E) The focal chalky-while dcposilS are arca" of fal necrosi" rcsulting fmm the rclcasc of pancrcalic 1ipa.'>Cs in palienls with aCUle pancrcalitis. ViT"dl hepatitis docs not cause nccrosis in Olhcr organs. and hcpatocyte necrosis fmm viral infcctions occurs mainly by mcaos of apoptosis. Inteslinal infarelion is a forro of coogulati"e necrosis. Tuberculosis prodoccs cascous nccrosis. Gangrcnous necrosis is mainly coagulative necrosis bUl occurs o"cr an exlensive arca.

6.

BP6 12-13 PBD6 16-17 7. (B) Intraccllular mechanisms cxist lhal deal with froe radical gencralion, as can occur with radiant injury from irradiation. Glutalhione pcmxidasc reduces such ¡njury by catalyúng lhe brcakdown of H 20 2• Phospholipases decrcase ceJlular phospholipids and promole cell mcmbrane injwy. Prolcascs can damage cell mcmbrnncs and cYloskcletal proteins. Endonucle.ases damagc nuclcar chromatin. Lactalc dchydrogenasc (LOH) is prcsenl in a variely of cclls, and ils e1cvation in the serum is an indicator 01" cell death.

BP69-11

PBD612-14


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Part 1

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GENERAl. PAlHOLOGY

8. (B) Mutations in thc o.~antitryJX"in gcne give rise lo O'.·amitrypsin molecules !hal cannol fold propcrly. TI1c par~ tially foldcd molceulcs accumulate in !he cndoplasmic re· ticulum (ER) and cannoc be sccreled. Impaircd dissociation of lhe cysLic fibrosis Ird.osmcmbranc conductance reE;ulator (CFTR) protein from chaperones is Ihc cause of many cases of cystic fibmsis. Thcre is no abnormality in lhe synthcsis 01' rnetabolislIl of o.-anlitrypsin in patients wi!h O'l-alltitrypsin deficiency.

14. (B) On DNA damagc induce<! by chcTl'lOlherapeUlic drogs lar other agcnts). nonnal p53 gcnes trigger lile cclls lO undcrgo apoptosis. When p53 is inaclivated. Ihis palhway of ccll dcalh can be blockcd. rendcring the chcmolhcr· apy les." effeclivc. bcl-2 and NF-KB favor cell SUlVival. Cytochromc P450 docs nOl arreel apoplosis. Granzyme B is faund in cylotoxic T cells and nol tumor cells. It lriggers apoptosis.

BP6 155-156 PBD625

PBDó 41 9.

(C) l'le ha... an acule rnyocardial infarclion. An ischemíe injury to most inlcmal organs PrOOuces a panern of cel1 dcalh calle<! coagulative necrosis. Liqucfaetive necrosis occurs following ischemic injury lo brain and is a1so the paltem secn wilh absccss formation. Cascous necrosis can be secn in various forms of granulomatous inflammation. Iypificd by tuberculosis. Fal necrosis is usually secn in panercas and breast tissuc. Gangrcnous necrosis is a fonn of coagulative necrosis lhal usuany rcsults from ischcmia and affects limbs.

BP612-13

15. (8) Lobulcs increase undcr hormonal influence lO providc for lactation. Thc breast stmma plays no role in lactation and may incrcasc in pathologic proccsscs. Epilhc· Iial dysplasia denotcs disordcred growlh aud maturation of cpithclial cclls that may progrcss lo cancer. Accumulation of fat wilbin lhe cclls is a common manifcslalion of sublclhal cell injury or. uncornrnmly. bccausc of inbom enors in fat metabolism. Epilhclial mctaplasia in thc breast is a palholOE:ic proccss.

BP6 22 PBDó 32-33

PBD616-1B

ID. (C) Rcduccd workload causes shrinkage of ccll sizc because of loss of cell substance, a proccs... callcd alrophy. Aplasia rders lO Jack of cmbryonic developmcnt; hypoplasia is uscd to describe poor or subnormal dcvclopment. OYSlrophy of mUliCles rcfcrs lO inheriled disorocrs of skclelal muscles lhat Icad to muscJe wcakncss and wa"ling. Hyaline changc is the name givcn lo a oonspccific. pink, glassy eosinophilic appcarance of cclls.

BP621-22 PBD6 35-36 11. (B) Genll cclls havc thc highest Iclomerase aclivity. and lhe tclomere lenglh thcrefore can be stabilizcd in Ihcsc cells. This allows genn ccl1s lO retain lhe ability to divide. NOfTllaI somatic cclls havc no Iclomcrasc activity, and telomeres progrcssively shoncn with each ccll division unlil growlh arrcst occurs.

PBD6 47 12. (C) Infiammation ha.. rcsultcd in rcplacemcnl of nor· mal squamous epithelium by intcslinal.lypc columnar epithclium with goblet cells. Such convcrsion of one adult ccll Iype lo anothcr typc is calle<! melaplasia. The thickness of lhe mucosa is normal. The lamina propria has sorne infiam· malory cclls bul ¡s not alrophic.

BP622-23 PBD6 36-37 13. (A) This is an cxample of orderly, prograrnmcd cell death (apoptosis) through hormonal stimuli. Tbc endomctrium breaks down. sloughs off. and then regcnerates. Cascous necrosis is Iypical of granulomatous inl1ammation. rcsulting masl common1y from mycobactcrial infcelion. HcterophagocYlosis is Iypificd by (he clearing of an arca of necrosis lhrough macrophage ingestion of Ihe nccrolic cells. Wilh ccllular alrophy, lhere is oftcn no visible necrosis. but the tissucs shrink in sizc. solTlCthing lbal would happen to lhe endomclrium after mcoopallse. Liqucfactivc necrosis can occur in any lissue after acutc bactcrial infcclion or in the brain after ischcmia.

BP6 13-14 PBD6 18-19

16. (E) Each unít of blood contains 250 mg of iron. The body ha.. no mcchanism for gctting rid of cxce.<;s iron. A small amounl of iron is losl with normal dcsquamalion of epilhclia, and mcnstruating womcn losc a bit morco Thc cxcc."s iron bccomc." storagc imn. 01' hcmosiderin. Over time, hcmosidemsis involvcs more and more tissucs of the body, particularly the liver. InitiaJly, the hemosiderin dc· posits are found in Kupffer cclls in lhe livcr and olhcr mononuclcar phagocytes in lhe bone marrow, spleen, and Iymph nades. Wilh grcal excess of iron. liver cells also accumulate iron. Stcalosis usually occurs with ingcstioo of hepaloloxins such as alcohol. Bilirubin. a breakdown prad. ucl of blood, can be passed out in lhe bile so thal a pcrson docs not bccorne jaundiccd. Amyloid is an abnormal proIcin derivcd from a varicty of prccursors such as imlllunoglobulin light chains.

BP6 19 PBD6 42-43 17. (C) Thc checsclikc appcarance gives Ihis form of IlCcrosis its name-caseous necrosis. In lhe lung, luberculosis and fungal infcetions are mast likcly to produce tbis pattem of tissuc injury.

BP613 PBD617 18. (K) Nodular prostalic hyperplasia (also-known as be· nign prost2tic hypcrplasia. or BPH) is a cornmon condilion in older males thal rcsullS froro prolifcralion of both prostatic glands and slroma Tbc proslalC bccomes more sensi· tivc to androgenic stimulalion with agc. This ¡s an example of pathologic hypcrplasia.

BP622 PBD632-33 19. (K) Thc livcr is one of the few organs Ibat can al leasl partially rcgencrate itself in thc human body. '1ñis is a form of compcnsatory hypcrplasia. Thc stimuli to hcpatocytc mitOlic aClivity cease whcn the liver has atlaincd its normal Si7.c.

BP6 22 PBDó 32 -33


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20. (A) Alrophy is oflcn associatcd wilh increascd deslruclion of subccllular components by aUlophagy. The cellujar components (e.g., mitochorKiria, endoplasmie reticulum) are digestcd by thc Iysosomal enzymcs. Sorne of thc cell dcbris resist digcslion and pcrsist as insolublc material in lhe Iysosomcs. Lipofuscin grdnulcs represenl undigesled material Ihal rcsults fmm lipid pcroxidation.

BP6 19 PBD6 26. 36 21. (8) This hislol~ic pieture is Iypical of apoplosis produced by chernothcrapculic agcnts. The release of cylochromc froro lhe milochondria is a key stcp in many fonns of 3poplosis. and il lcads to the aclivation of caspases. bc/2 is an anliapopc.ooc protein that pre\-'Cnts eytochromc e releasc and prevenls caspase aetivalion. lipofuscin is a pigmenlcd rcsiduc represcnling undigestcd cellular organelles in aUlophagic vacuoles. Catala.se is a sca\'enger of H2 0 2 • Phospholipascs are activatcd during necrosis and cause cel1 mcmbranc damagc.

BP6 13-15 PBD6 22-24 22. (O) Mela~al)c calcification of lissucs occurs whcn therc is markcd hypcrcalccmia, and calcium is precipitatcd within interstitial tissues. panicularly the lung. kidney, aOO stomach. Hypcrcalccmia can have a variclY of causes, inc1uding hypcrpardthyroidism, bemc dcstruetion duc lo metastases., pamneoplastic syndromcs., and, lcss cornmonly, vitamin D intoxication or sarcoidosis. Tuberculosis of the lung rcsults in cascous necrosis aOO dyslrophic caicificalion in the damagcd tissucs. Pancrcatilis may be thc result of hypcrcalcemia, bul the pancrcas demonslrates fal necrosis that may dcvc10p dyslrophic calcification. So-<:alled senile calcific aortie Slcnosis is a form of dystrophie ca!cificalion in a persan whosc scrum ealcium Icvc1 is normal. With amyloidosis., lbere is dcposition of rnc amyloid protein in a variety of tis...ucs, bul calcification does nol occur, and hypercalccmia is not a complicalion.

BP6 20 PBD6 45 23. (O) Thc high lipid contcnt of cenlral ncrvous syslcm (CNS) tissucs rcsulls in liqucfaclive nccrosis a'l a consc· qucncc of ischcmic ínjury, as in Ihis case of a "slrokc.'· Fal necrosis is secn in brea'lt and panercas lissucs. Coagulativc necrosis is the Iypical resull of ischcmia in moSl: solid organs. Apoptosis affccts singlc eclls and typieally is nOl grossly visiblc. Karyolysis refcrs lo fading away of ccll nuclci in dcad eclls.

BP612-13

PBD6 16-17

24. (C) This is fally changc (steatosis) of thc livcr. wilh lipid vacuolcs secn in many of thc hcpatocytes. Abnormalilies in lipoprol.eín mctabolism can Icad to steatosis. Alcohol is a hcpalOloxin thal produces hcpalk stcatosis. Occrcased scrum albumin Icvels and incrcascd prOlhrombin time suggest alcohol-induccd livcr damage. Drug abuse wilh hcroin has surprisíngly few organ-spccifie pathologie findings. Exercise has linle dirccl cffcct on hcpatie function. Smoking dirccl1y damages lung lÍssue bol has no direct cffcet on the li\-cr. Aspirin has a significant cffccl on platclct funclion. not on hcpatOCYles.

BP617-1B PBD639-40

CELlULAR PATHOlOGY

9

25. (A) This ccll is shrunkcn and convcrtcd imo a dcnse eosinophilic mass. The surrounding eclls are normal, and lhcre is no inftarnmalory reaction. This pauern is typical of apoplosis. Ca..pasc activalioll is a univcrsal feature of apoptosis, regardlcs... of the iniliating causc. Rcduccd ATP synIhcsis and incrcascd glycolysis oceur whcn a cell is subjcclcd to anoxia. Thcsc changes are reversiblc. lipases are activalcd in enzymatic fal necrosis. lipid pcroxidation occurs whcn rnc ccll is injurcd by free radicals.

BP6 13-14 PBD6 lB-20 26. (O) Upofuscin is a "wcar and tcar" pigment lhal increases wilh aging, particularly in Ih'cr and in myocardium. 'Thc pigmenl has mínimal effcet on ccllular function in lTlOSl cases. Rarely, Ihcre is markcd lipofuscin dcpositioo in a small hcart. a so-called brown atrophy. Mc1anin pigmcnt is responsiblc for skin tonc: the more mclanin, the darker lhe skin. Hcrnosidcrin is the brcak.down product of hcmoglobin that contains the iron. Hearts with cxccssive iron dcposilion Icnd to be large. Glycogcn ís increased with sorne inhcritcd enzymc disordcrs ando whcn thc hcart is involved. increascs hearl sizc. Bilirubin. anolher breakdown produet of hcmoglobin, impans a )'ClIow appearancc (icteros) lo tissues.

BP6 19 PBD642 27. (A) AnthracOlic pigmcntation ís common in lung and hilar Iyrnph nodcs. Thís is carbon pigment inhale<! froro poIluted airo 'Thc lar in cigarcue srnokc is a good sourcc of such carbonaccous pigmento Hcmorrhagc can resolve, with formalion of hemosidcrin pigmcntalion lhal imparts a brown color to lissucs. Hepalic failure may resull in jaundicc, with a yellow color. Oldcr persans gcnerally havc more anlhracolic pigment, bul this is not inevitable wilh aging-pcrsons living in ru....a1 arcas will havc Icss. Meta'ilaseS impart a lan lO white appearance lo tissucs.

BP6 19 PBD642 28. (O) DcJXlsilion of ca1cium in normal hcallhy tis."Ucs from prolongcd hypcrca1ccmia is callcd mclaslalic calcification. This roay occur in hyperpamthyroidism. DYSHOphic calcification rcfcrs lo calcium dcposition in injured tissues, with nonual scrum calcium Icvcls.

BP6 20 PBD6 45 29. (O) Thc loss of lhe fllK"leus rcsults in ecll dcath. AII othcr ccllular morphologic changcs represenl rcversiblc ccllular injury. Thc plasma mcmbrdnc and intraccllular organelles remain funclional unlcss scvere damagc causes loss of mcmbrane inlcgrity.

BP611-12 PBD6 B-lO 30. (8) Rcpcrfusioo injury is c1inically importanl in myo-cardial infarction and stroke. Paradoxically. the oxygcn lhal flows in with blood can be eonvcrtcd to free radicals by parcnchymal and cndolhelial cells and infiltrating lcuko-cytes. Calalasc is a scavcnger of free radicals. AII Olher changes listcd oceur in sublclhal ccn injury.

BP6 11

PBD6 14-15

31. (8) Thc dccp cosinophilic st31mnlh loss of nuclei, and the loss of cell stroeture suggcst an car1y ischcmic


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GENERAl PATHOlOGY

injury, resulting in coagulati\'c necrosis. This is Iypically causcd by Iuss of bloud llow. Viral infcclion could cause necrosis of Itlc myocardium. bul this i!l usually accompanied by an inflammatory intillralc consisting of Iymphocyles and macrophages. Blunl trauma produces hemorrhage. An immunoJogic injury may produce focal ccll injury bul nol widespread ischemic injury. Lack of prolein 1cads to a calabulic slate wilh gradual dccrcasc in cell si7-c but it does nol cause ischcmic changes.

BP66-7 PBD67 32. (O) The incrcase in ulerine size is primarily thc resull of ao increa."C in myomclrial smooth musclc ccll sizc. lñc endometrium also incn::ascs in size. bul il remains JUSI a Jining lO the muscular wall aOO docs na COfltributc as

much lo lhe sizc changc. Thcre is little stroma in myomclrium and a grcatcr proportion in cndomclrium., bul this contribules a smaller pcrccnlage lO thc sizc gaio than docs muscle. 'loe yesscls are a mil"l(r bul csscntial componenl to Ihis proccss.

BP622

PBD6 33-35

33. (A) Heteroph<lgocytosis by macrophages requircs Ihal endocylOsed \'acuoles fuse with Iysosomcs lO degrade !he cngulfed material. With congcsli\'c failure. extra\'asalion of red blood cclls (RBCs) into ah'OOli occurs. and pulmonary macrophagcs musl phagocytosc thc RBes. breaking down thc hcmoglobin and rccycling tIlc ¡ron by hemosidcrin formatioo.

BP6 15-16 PBD625-26


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CHAPTER

2 Acute and Chronic Inflammation PBD6 Chapter 3 - Acute and Chronic Inflammation BP6 Chapter 2 - Acute and Chronic Inflammation

l. Thc products of the complemenl system are involved in aH of the following SICpS oc phases of the inflammalory response acepl Chcmotaxis lncrcascd vascular pcrmcabitily Ncutrophil aetivalion Phagocylosis O (E) K..illing of bactcria in lhe phagocylic vacoole

O (A) O (B) O (C) O (O)

2. After the ieukocytcs Icave thc vasculaturc. their migrdtion in tissues to the sitc of infection or injury is mcdiatcd by which of the following subslanccs aeting a.. a chemotactic faclor? O (A) Bradykinin O (B) Chemokines O (C) Histaminc O (O) Prostaglandins O (E) Complcment C3a 3. A 53-year-old fcmalc has had a high fevcr wilh cough producti\'c of yellowish sputum ftt the past 2 days. Auscultation of the chcst CC\"Ca!s a fcw crackles in both lung bases. A chc.~ radiograph ccveals bilatcral palchy pulmonary infiltrales. Which of the following inflammalary cell typcs will be secn in grcatly increascd numbcrs in a spulum spccimcn? O O O O O

(A) Macrophagcs (B) Neulrophils (C) Mast cells (O) Sm31\ Iymphocytcs (E) Langhans gianl cclls

4. Two weeks afier 3n acutc myocardial infarelion. the nccrotic myocardium has largcly becn replaccd by capil-

laties. fibroblasts, and collagen. A v3riety of inflarnmatory cclls are presenl. Which of thc following infl3mmatory ccll I)'pes in such a Jcsion plays an imponant part in the hcaling process? OCA) M3croph3ges O (B) Pla"ma eells O (C) Nculrophils O (D) Eosinophils O (E) Epilhclioid eells 5. Aspirin is oflen uscd for its anti-inllammatory effects. Which of the following fcatures of the inflammatory response is affected by aspirin? OCA) O (B) O (q O (O) O CE)

Vasodilation Q:¡cmotaxis Phagocylosis Ernigration of leukocyles Relea~ of leukocyte." from the bonc manuw

6. A 6-year-old male ehild prescnts with a history of recurrent infeetions with pyogenie bacleria (e.g.• SUlphyloCOCCIl.5 (/l/reus. Streprococcw; pemUlllmiae). Afler infec· tions. thcrc is an expected increase in the tolal white blocx:l ecll (WBC) count and l'lCulrophilie leukocytosis. However, histologie examination of lissucs revcals very fcw neulrophils. An analysis of patient's ncutcophil function in spe· cíally eonstructcd tohcs lincd with human cndolhclium shows a defccl in rolling. A dcfect or dcficicncy affecting whieh of the following molecules is likcly to be responsible for the increascd susccptibility to infcction in lhis palicnt?

O CA) Selectins lmcgrins O (C) Leukolrienc B4 O(D) C3b O (E) NAOPH oxidase

0(8)

7. A 32-year-old fcmale has had 3 ehronic cough wilh fever for lhe past monlh. A chcsl radiogrnph shows many small. ill-defincd nodular opacilies in all lung ficlds. A lransbronchial biopsy reveals intcrslilial infiltrates wilh Iymphoc)'tes. plasma cells. and epithelioid macrophages.

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Port 1

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GENERAl PATHOLOGY

Which of lhe following infcctious agcnls most likcly caused this appcarance'! OCA) SlaphyloclJCCI/S allreus O (B) Pla.ollodilUn falcipamm

O (C) Candida albicans 0(0) Mycobacleriwn 1uberClf/o.fi.f O (E) Kleb.fie/la pneu/Ilrmiae

8. A 36-ycar-old male ha"> expcrienccd mid·epigaslric abdominal pain for the paSI 3 months. Uppcr endoscopy reveals a 2-cm ulccralion of !he gaslric antrum. A biopsy of the ulcer shows angiageocsis with fibrosis and mononuc1ear ccll infiltrntcs with Iymphocylcs. macrophagc.... aOO plasma rells. Thc best rerm for Ihis pathologic process is OCA) Acule intlammalion O (B) Seruus inflammluion O (e) Granulomalous intlammatioo 0(1» inllalllmation O (E) Olronic inflammatioo

".brinous

For cach of the descriptiolls of an inAammalory response in qucslions 9. 10. and 11. match the most c10sely associaled leltered chemical mediator invoh'cd wilh lhe re· sponsc. (A) BraJykinin (8) Chemokines (C) Complemt:1lI C3b (O) Complemenl C5a (E) Lcukolricncs ( ..,

Hislamine

(G) lnlerferon-')' (H) Interleukin-l (1) Myclopcroxidase (1) Nilric oxide (K) Oxy~'Cn mclaoolilcs (L) Phospholipase C (M) Plalclcl-aclivating faclor (N) Substnncc P (O) Tumor necrosis faclor 9. Lymphocyles are aclivated by conlact wilh antigcn aOO lhen bcgin lO produce a subslance lhal is a major stimulatar of mooocytes and macrophages. ( ) 10. A 41-year-old roan ha"> a severc hcadachc, A lumbar pun<.1urt: is pcrfonncd. and the ccrebrospinal fiuid oblained has a rell counl of 910 \VBCslmm~. with diffcrcntial count of 94% nculrophils and 6% Iymphocytcs. InflammalOl)' mcdial<m> are rclcascd thal cause him lo dcvclop a rcvcr I with tcmpeT3lUrc of 39.rc. (

of the hcalcd righl lowcr quadrdnl iocision. Thc nodulc is cxciscd and microscopically shows macrophages. collagcll. a fcw small Iymphocyles, a.nd giant rells. Polarizablc. refractile material is in lhe ncx:lulc. Which of the following complicalions of her surgc!), bcst accounls for !hese findings? O (A) Chronic inflammalion O (B) Abscess formation O (C) Sulure granuloma O (O) Ulceration O (E) Edema

13. A dcfcct in which of !he folJowing slepS of inflamma· lory response is responsible for !hc incrcascd susccplibililY lo infcelion sccn in palienls wilh chronic granulomatous disease? OCA) AClivalion of rncw;:rophagcs by inlcrfcron-'}' O (B) Oxygcn-dcpcndcnt killing of bacleria by nculrophils adhcsion bclween IcukOCYles and cndOlhelial O (e) cdls 0(0) Synthesis of Iysozymc in neulrophil granules O (E) Opsonization of bacteria by immunoglnbulins

".rm

14. During acule inllalllmation. there is a "bursl" of oxY· gcn consumplion (rcspiratory burst) in ncutrophils. This is an esscntial step for which of the following evcnts? O (A) Incrcased production in the bemc nllUTOw O (B) Altachmcnl lo thc cooothclial cclls O (e) Opsonizalion of bacteria O (O) Phagocytosis of bacteria O (E) Gcncralion of microbicidal activity 15. A 20-year-old. scxually promiscuous fcmale cxpcricnces lowcr abdominal pain of 24 hours' durdtion. Thcle is no previous history of pain. Shc is fcbrilc and ha<¡ a markcdly lender lowcr abdomcn on palpation_ The tOlal WBC is 29.lXXlImm.l. wilh 75% neutrophils. Laparolomy revcals a dislended. fluid-lilled, rcddcncd len faJlopian lube !hal is aooul to rupturc. The lube is removcd. ~Iislologic examination of Ihe fallopian Iube is likely to rcveal all of Ihe following excepl OCA) O (B) O (C) O (O)

Nculrophilic infi!rralc Fibroblaslic prolifcralion Exudation of fibrin Necrosis of mucosa O (E) Oilatcd blood vcsscls full of red cclls 16.

A chcst radiograph of a 9-year-ol.d malc infccled with

A1ycobaclerilU1I tllberclllosis revcals cnlargcmcnl of hilar

Iymph nades. lñcre is ~rranulomalOlls inf!arnmation w¡thin thc nodcs. marked by the prcscncc of Langhans gianl cclls. Thc mcdilltor Ihat most aids in this gianl eell formal ion is

11. A wOll1an who dislikes eats bccause she is allcrgic to lhcm visits hcr ncighoor. who ha.. sevcral cal,,> in !he housc. Of cour'SC. one of lhe cats immcdialely jumps inlo her lap. The cal dandcr is inhalcd. and within minutes. she i5 snce:zing and dc,'clopS nasal Sluffincss wilh abundant nasal secrclions. Thc masl cdls have releascd a mcdialor lO produce ¡hcse findings. ( )

O (B) Complcmcnt CJb O (C) LcukOlrienc B4 0(0) Inlcrfcran-'}' O (E) Inferleukin-I

12. A monlh aftcr an appcndcctomy. a 25-year-old woman palpaK'S a small nodulc bcncath the skin al thc sile

17. A palient wilh recurrent baclerial ¡ofcetioos is lliagnoscd lO havc a gcnctic dcficicoc)' in myelopcroxidasc. Thc

O (A) Tumor necrosis faclor


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cause of incrcascd susccptibilily to infcclions is OCA) Dcfcclivc nculrophil dcgranulation O (B) Dcfcclivc production of proslaglandins O (e) An inabitity to producc hydroxy-halidc radicals 0(0) Dccrcascd oxygen consump(ion after phagocytosis O CE) An inability to produce hydro,gcn pcroxide

ACurE AND CHRONIC INFLAMMATION

13

98% ncutrophils and 2% Iymphocytcs. A Gram stain of this fluid rc"cals gram-posilive cocci in c1ustcrs. { )

18. A 78-ycar-old femalc suffcrs a strokc. with loss of movemcnt on the righl sidc of hcr body. She is found lo havc an occlusion of lhe Icn middlc cerebral artery. To prevem furtllCr ischemic injury. which of thc following mcdiators woold be mosl bencficial?

OCA) Thromboxanc Al O (B) Bradykinin O (e) Nilric oxide O (O) Plalclcl activaling factor O (E) Lcukolricnc E. For lhe c1inical histoOe.'i in qucstioos 19 and 20, match the most c10scly associaloo leHered inllammatory response. (A) Absccss (B) Cascating granuloma (e) Chmnic inl1ammation (O) Edc"", (E) fíbrinous inflammation (1-1 Fibrosis (G) Foreign body granuloma (H) Lymphadcnitis (1) Purulcnt exudatc (1) Rcgcncration (K) Scrous cffusion (L) Ulccration

A 43-year-old malc has had a coogh with fever for lhe pre\'ious 2 momhs. A chcst radiograph rc\'cals nodular densitics, sorne wilh calcificalion, localcd mainly in the upper Jobes. Thc microscopic appcarance of a lung biopsy is shown. Wllich of the fo1Jowing chemical mcdialors is most importam in lhe pathogencsis of Ihis Icsion?

21.

OCA) O (B) O (e) O (O) O (E)

Complemcnt CSa Inlerfcron-'Y Bradykinin Nilric oxidc Proslaglandin

22. A 59-year-old ma1e has had a cough with fever for (hc pa...t wcck. A chest I'8diograph rcvcals a righl pleural tluid oolleclion. A right thol'8centesis yic1ds 500 mL of c10udy yellow nuid. Which of thc followin,g cell typcs is masl likcly lo be abundant in Ihis fluid? OCA) Macrophagcs 0(8) Ncutrophils O (e) CD4 Iymphocytcs

O (D) Plasma cclls O (E) Eosinophils 23. A 5-ycar-old child reachcs up lO thc stove and tooches a pol of boilin,g soup. Within scvcral hours, Ihere is marked erythema of the skin of thc fingcrs on the right hand, and small blisters appcar on (he finger pads. Which of the fol1owing lenn.'i best describes Ihis process? 19. A 50-year-old man whu has cxpcricnccd midabdominal pain for severa.! wccks is fooM to ha"e occult blood-positivc stool. en uppcr cndoscopy, he is foond lO ha"e the duodenal Icsion depictcd microscopically in thc figure. ( ) 20. Thoracentcsis is pcñormcd en a 70-year-old woman. and 800 mL of c10udy )'cllow fluid is oblaincd from the left pleural cavity. A cell count en (his fluid TC"eals 2500 whilc blood cellslmm). with a differential count of

O (A) O (B) O (C) O(D) O (E) 24.

Fibrinoos inl1ammalion Purulent inMammation Scroos inllammation Ulceration Granulomalous inMammatioo

Two wceks aftcr a 90-year-old female wilh Sraphyloaflrelts pncumonia rcceivoo a course of antibiotic therapy, shc no longcr has a produclivc oough, bul she stil1 has a fc"er. A CheSI radiograph TCvCalS a km, roundcd

C.VOCIIS


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K".nn~

Parl 1

nlAJlWl>'l ! >

GENERAl PATHOlOGY

densil)' in thc righl lowcr lube whose liqucficd COOlcm,<; form a cenlral air-fluid leve!. Therc are no sunounding infihrates. Whal is lhe besl descriplion for this nulCome of hcr pneumonia?

O (C) Leukotrienc E. 0(0) Hislamine O (El Nilric oxide

OCA) Complele rcsolulion O (B) Rcgcncralion O (e) Fibrosis O (O) Absccss formation O (E) Progressiun lo chronic inflarnmalioo

29. A paticnl wilh righl \'entricular faiJure (congcsli\'e hcan failure) deve10ps fCVCT and accumulalion of fluid in !he pleural space. Thc fluid ha" a high spccific gravity (1.030). aOO il COOlains dcgeneraling neulrophils. 1lle rnosl like1y cause of fluid occulllulation is <In ¡l/crease in

25. A 30-year-old fcmale who has a history of (;Ongenilal hear1 disease with a venlricular septa! defccl prescnts wilh persistent fever and headache. A head compuled tomography scan TC"cals an abscess in thc righl parietal labe \hal is 3 cm in diameter. Which of lhe following actions by inf1ammalory cells besl aceoonts for absccss formation? OCA) Formation uf nitric oxide by macrophagcs O (B) Production of interfcroo-l' by Iymphocyles O (O Fonnation of TGF-j3 by macrophages O (D) Generalion of prostaglaTKlin by cndothclium O (E) Rdea-.e uf Iysosomal cnzymcs from neulrophils 26. A Chesl mdiograph of a 35-year-old male demonstr<LlCS large, bilateral pleural effusions Iha! have accumulaled in the past 24 hnllrs. Thoracenlesis is pcrformed. and 500 mL of slighlly c10udy yelJow fluid is removed. Cylologie examinalion of lhe Iluid reveals lIléln)' neutmphils huI no lymphocYles or red blood reUs. Which of lhe following rnechanisms conlribol~ lo lhe accumulalion of lhe fluid in the pleural space?

O (Al Colloid osmolic pressurc O (B) Lymphatic pressurc O (C) Vascular pcrmcability 0(0) Renal retention of .I¡()()ium and water O (E) Lcukocylc... 30, A 5-year-()ld child who prcscnts wi!h history of recurrent infeclions wilh gram-posilive bactcria such as Swpl!ylOCOCCIlS allrt!IlS i!> found lo have a gcnclic lock of J3.z~inlegrins. Which of !he following abnonnalities of ncutmphil funclion is rcsponsible for his c1inical symploms?

O (A) Neulrophils show normal "rolling" bul inadequale sticking on cylokinc-aclivaled endothe1ia! cells O (B) Failurc of lhe neutrophils to migratc lO lhe sitc of infcctiOll after leaving Ihe vasculalure O (e) Rcduced rcspirdlory bursl in lleulrophils after phagocYlOsis of bacteria 0(0) J)iminished phagocylosis of bacleria opsonizcd wilh immunnglobulin G O (E) Failure to gencrate hydroxy-halide radical... (HOCI)

O (A) Arteriolar vasoconstriclion

O (B) NeutrOphil release uf l}'sosnmo. O (e) Endolhelial conlraction 0(0) Inhibilion of plncelel adhcrencc O (E) Lymphalic obstrocliOll

27. A 12-monlh·old child \Vith n 6-month hislory of repealed infeclinns prescnls with a lung infeclion and elevaled nUl11bcrs of ncutruphils in periphernl blood. Aspiralion of a lung abs<:css shows accumulaliun 01" neulrophils. Ll.Iboralol)' studies dClllonstrate Ibat his ncutrophils phagocylose and kili organisms normally in Ihe pTCSCnce of norm.11 human scnJm (bul 001 palienf s seTUm). They migratc nonnally in a chemolaxis assay. Which of the following is lhe mosl likely cause for lhe increase<! suscepübilil)' to infeclion" O O O O O

(A) (O) (C) (O) (E)

Deticiency of inlcgrins Neultophil microtubular protein def~1 Immunoglobulin dcficieocy Defectivc llCutrophil Hl~ generalion Dcficiency of se1eclins

28. A 35-year-old female takcs aspirin for hcr arthrilis. Allhollgh her joint pain is reduced wilh lhis therapy. lhe inlll.llllmalory process conlinlles. Thc aspirin lhcrapy alleviales her Jl<lin mainly Ihrough reducliOIl in (he synthcsis uf which of the following mediators? OCA) Comptemenl Clq O (B) Proslaglandins

ANSWERS l. (E) Complemcnt compOncnt.'i are not involved in thc killing of bacleria within lcukocytes. The componcnls of complcmcnt cireulate in pla~rna and can be found in exudcd plasma al silcs of inflammation, bul thc...e eornponcnts are not found intracellularly. The mcmbrallc aUack complex formcd by C5-9 can kili bacleria eXlracellularly, C5a is a powerful chcmotactic agen!. and it causes ncutrophil aetivalion. C3a an<! C5a incrcasc vascular pcrmcability by causing release of hiSlaminc from mast cclls. C3b is an opsonin.

BP635-36 PBD6 67-69 2. (8) Chcrnokincs include a numbcr of molecules thal are chemolaclK: for ncUlrophils, cosinophils. lymphocytcs, monocytes, and basophils. Bradykinin causes pain an<! increascd vascular pcrmcability. Hislaminc causes vascular leakage. and prostaglandins have Illulliple actions. bul they do not cause chcmotaxis. C3a causcs increascd vascular pcrmcabiJity by rclcasing hislamine from masl cells.

BP631

PBD661

3. (B) 1lle signs and symptoms suggc.~t an acule bacterial pncumonia. Such infcclions induce an acute inflammalion dominaled by neutrophils, which gives thc spulUm t.hc yel-


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lowish, porulent appcarance. Macrophages bccome more numerous ancr lhe acute evcnts alJd clcan up the dcbris through phagocytosis. Mast cclls are beuer known as par~ ticipanls in allergic and anaphylaclic responsc.o;. Lymphocytcs are a fcalure of chronic inflammalion. Langhans giaot cclls are secn wilh grnnulomatous inflammatory responses.

BP6 26 PBD6 51 4. (A) Macrophagcs. prescnt in such Icsioos. play a promincnt role in tite healing proccss. Activatcd macrophages can secretc a varicty of cylokincs lbat promete angiogcncsis and fibrosis, including platelct-dcrivOO growth factor. fibroblasl growlh factor. interleukin-I, aOO tumor nccr~is faclor. Plasma cells can secrete immunoglobulins aod are not instrumental to healing of an area of tissue injury. Thc llCutrophils are mast numerous within the initÍal 48 hours afler infaretion but are nol numemus after the first week. Eosinophils are mosl prominenl in allergic inflammaliolls and in parasilic infcctiOlls. Epi!.hclioid cclls. which are aggregalions of aetivated macrophages. are Iypically secn wilh granulomatous inllammalion. Thc hcaling of acute inflarnmatory proccsses docs nOl involve granulomalOUs inflamrnatioo.

BP641-42

PBD679-BI

5. (A) Aspirin (acctylsalicylic acid) blocks thc cyclooxygenase pathway of arachidonic acid melabolism. which leads to rcduecd prostaglandin gcncration. Prostaglandins promol.e vasodilation at sites of inflammation. ChcfTl()(axis is a function of various chemokincs. and oomplemcnl C3b may promote phagocytosis. but ncithcr is affcetOO by aspirin. LeukocylC cmigrntion is aidcd by various adhesioo molceules. Leukocyle relcasc from the marrow can be dri"cn by mc cytokines interleukin-I and lumor necrosis faclor (TNI-'J.

BP6 37 PBD6 71- 72 6. (A) The palicm has a defoct in Icukocylc rolling. !.he first step in lransmigration of neulrophils from the vasculaIUre lo the lissues. Rolling depcnds on interaction bctwecn sc1cctins (p. and E-sclcctins on endolhclial cclls. and L· sclcelin on neu!rophils) and their sialyated Iigand molceules (e.g.• sialyated Lcwis X). Integrins are involved in Ihe nex! SlCp of tr.msmigralion. during which thcre is 11m adhcsion bctwccn ncuttophils and endothclial cells. Lcukotriene 8 4 is a chemOlactic agenl. C3b facililatcs phagocytosis. and NADPH oxidase is involvOO in mH:mbicidal aClivity.

BP62B-29 PBD6 58-63 7. (O) Her disease has fealures of grnnulomatous inflammation. and tuberculosis is a oommm cause. Bacteria such as SUlfJlJ)'lococclIs and Kfebsiel1n are more likely to produce acute inflammalion. Pfasmodi/llll produces malaria, which is a parasitic infcetion wilhol\l a signirJCafll degrce of lung invol\-cmcnL Cnndida is often a commcnsal organism in the oropharyngeal region and rarcly causes a pncu~ monia in hcalmy (nonimmuoosupprcsscd) individuals.

BP642-43 PBD682-83 8. (E) One of the oulcomes of acute inllammation with ulceralion is chronic inllammation. This is particularly troe

ACUTE AND CHRQNIC INFlAMMATlON

15

when lhe infiammatory proce.o;s continues for wceks to months. Chronic infiarnmation is chardCterizcd by lissue deSllUCtion. mononuclcar cell infiltralion. and repair. In acule inflammalíon. thc hcaling proccss with fibrosis and angiogcnesis has not slartOO. Scrous inflammation refers to an inflarnmalOl)' process im'olving a mesothelial surfare (e.g., linin!,!. of lhe pericardial ca\'iIY). with an outpouring of fluid having little protein or ceUular content. Granulomatous inflammalion is a spceial form of chronic inflammalion in which epithelioid macrophagcs forro aggrcgates. With I1brinous inftammation, typically involving a mesothelial surface. Ihcrc is an outpouring of protein-rich fluid that rc.o;ults in prccipitation of fibrin.

BP6 41

PBD679

9. (G) lntcrfcron-)' secretcd from Iymphocyles slimulales monocyles and macrophages. which lhen secrete Iheir own cYlokines Ihal further activate lymphocYles. Imerferon-)' is also importanl in transforming macrophages jnto epithclioid cclls in a gnlOulomatous infiammatory response.

BP6 42 -43 PBD6 B2 - B3 10. (H or O) Fe,'er is produccd by a varicty of infiamIllatory mcdiators. but lhe major cytokines mat produce fevcr are intcr1eukin-1 and tumor necrosis factOl". prodoocd by macrophages aOO othcr cell types.. Interlcukin-I aOO lumor necrosis factor can have aulocrinc. parncrinc. and cndocrinc effects. They mcdiate thc acUle phase responses.. such as fever. nausea, and ncutrophil release fmm marrow.

BP6 40 PBD6 78 11. (F) llislamine is foond in abundancc in mas! cclls., normally prescnt in conncctive lissues ncxt to blood vcsscls bencath mucQWlI surfaccs in airways. Binding of an antigen (j.c.• allergen) to IgE anlibodics that have prcvioosly al· lachcd to the masl cel1s by Ihe Fc receplor triggers masl ccll degranulation. wilh release of histamine. This response causes increascd va'iCular pcrmcability and mucous sccreliollS.

BP6 34 BPD6 66 12. (C) Thc polarizablc malerial is the suture. and a giant cel1 reaction. typically with foreign body giant cells. is characteristic for a granulomatous reaction lO foreign material. Chronic inftarnmalion alone is not likely lO produce a localiz.cd nodule wilh giant cells. An absccss. t}'pically from a wound infcetion, shoold have liquefactive necrosis aOO numcrous llCUlrophils. An ulceralion involvcs loss of epidermis or other epithelial laycr. Edema refers to aocomulation of !luid in the imerstitial space. It docs noI produce a ccllular nodule.

BP6 42 -43 PBD6 83 13. (U) Chronic granulomatous discase is characterizcd by reduccd killing of ingeSlCd microbcs bccause of inheritOO dcfcets in me NADPH oxidase syslem. This syslem generates supcroxide anions (0 2 ). esscntial for me subscquent producrion of microbicidal product<; such as H202> OH, and HOCl-. Firm adhesions bctwccn leukoc)1es and


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GENERAl PAlHOlOGY

endothelium are impaired in leukocyte adhesioo deficieocy tylJe 1, in which there is a mutation in lhc beta chain of integrins. Lysozyme contained in neulrophil granules is re· sponsible for oxygen-indepeOOent killing of bacteria Impairtd opsonization can lead to infections in states of immunoglobulin deficiency.

19. (1..) Inflarnmation involving an epithelial surface may produce enough necrosis so that the sunare becomes eroded and is last. 'Ibis forros an uleer. If lhe inftammalian COfllinues, the uleer can conlinue lo penetrale downward imo submucosa and lIluscularis. Altematively. the uleer lIlay heal or may remain chronically inflamcd.

BP632-33

BP6 45 PBD6 B5

PBD6 62-65

14. (E) The oxidative bursl generates the reactive oxygen specics (i.e., superoxide anion) thal are impo",,"1 in destruction of engulfed bacleria. Myelopoiesis does nol depend on generation of superoxide. EndOlhelial allachmenl of neulrophils is aided by adhesion molecules on the elld~ thelium aOO the neulrophil surface. These molecules inelude seleclins ami inlegrins. Bacleria are opsollized by complemenl Ob an<! immunoglobulin G, allowing tbe bacteria to be more readily phagocytosed. BP632-33 PBD6 62-64 1S. (B) This is an acute inflanunatory response. with edema, erytbema. aOO pain of short duration. Fibroblasts are more likely panicipants in chronic inflammatory responses and in hcaling responses, generally appearing be· yond a week after lhe inilial event.

BP640-41

PBD6 7B- 79

16. (D) Inlerferon-y is secreted by activated T cells and is all importanl medialor of grnnulomatous illflarnmation. 11 causes activalion of macrophages and Iheir lmnsformalion into epithelioid rells and gianl cells. Tumor necrosis factor can be secreted by aetivated macrophages and induces activalian of Iymphocytes and proliferation of fibmblasts, other elements of a granuloma. Complement Ob acts as an opsonin in acute inflammatory reactions. Leukotriene B. induces chernotaXis in acule inflanunatory processes. Inlerleukin-I can be secrete<! by macrophages lo produce a variely of effects, induding fever, leukocyle adherence, fibroblasl proliferation_ and cytokine secretion.

BP642

PBD6 B2-83

17. (C) Myeloperoxidllse is present 111 ¡he azurophiJic granules of neutrophils. It converts H10 2 inlo HOCI , a powerful oxidanl aOO anlimicrobial agem. Degranulation occurs when phagolysosomes are fonned with engulfed bacteria in phagocylic vllcuoles wilhin lhe neulrophil cyt~ plasm. In contrasl. ptosfagL1ndin production dependo¡ on a fullCliooing cyclooxygenase pathway of arachidooic acid melabolism. Oxygen consumption \Vith an oxidative bursl after phagOCYlosis ¡s aided by glucose oxidalion and aClivalion of neutroptlil NADPH oxidase, resulling in generalJon of superoxide Ihal is convcrted by sponlaneous dismutalion lO H20 1 •

BP6 32 -33

PBD6 62-64

18. (C) Endothelial (:ells can rclease nilric oxide to produce vasodilation. Nilric oxide can also be administered to palienls to promote vasodilation in areas of ischemic injUl)'. Thromboxane A2• plalelet acllvating faclor. and leukolnene E. have vasoconstricli\'e properties. Bradykinin mainly increases vascular permeability aOO produces pain.

BP63B-39 PBD6 75

20. (1) Sorne bacleria evoke an acutc inflammalOry response dominale<! by neutrophils. The exlravao¡aled neulrophils altempl lo phagocylose and kili Ihe baCleria. In lhe process. some neulrophils die. and ¡he release of lheir Iysosomal enzymes cun cause Iiquefactive necrosis of the lissue. This liquefied lissue debris and the 1Í\'e and dead neutrophils cornprise "pus," or purulenl exudale. Such an exudate is typical for bacterial infeClions lhat involve body cavilies. This infeclion pmbably spread from lhe lung.

BP645 PBD6 84-B5 21. (8) This is a granuloma wilh many cpithelioid cells and prominenl large Langhans gianl ceUs. Macrophage slimulalion and lransfonnation lo epithelioid cells and giant cells are characleristic of granuloma fonnation. Inlerferon-y pmmotes the formation of epithelioid cells aOO gianl rells. Complemenl CSa is chemolaetic for neulrophils. Allhough occasional neutrophils are seen in granulomlls, neulrophiL~ do not fornl a major componen! or granulomatous infiarnmalioll. Bradykinin. released ill acute infiammalory responses. results in ¡Xlin. Macrophages can release nilric oxide to deslroy othcr rells, but nitrie oxide does nol slimulale macrophages to form a granulomalous re5pOf1se. Prostaglandins are mainly in\'oh'ed in lhe causalion of vasodila· lion and pain in acule inflarnmalOf)' responses.

BP642-43 PBD6 83-84 (8) His fiodiugs suggesl un acule inflammalory process, dominaled by the presence of neutrophils. As this

12.

process resolves, the number of macrophages will increase. Chronic inflammatory cells, including Iymphocytes aod plasma ceUs, may be few in number bUI are nOl necessarily absenl from aclll.e inflammalory processes. Eosinophils t0n11 ¡he minorily of acute innammalO!)' infihmles unless allergic or parasitic stimuli are presen!.

BP6 45 PBD684-B5 23. (C) Serous inflammation repre.-.ents the mildesl form of acUle illflammalioo. A blisler is a good example of serous inflammalion. It is associated primarily wilh exuda· lion of fluid into !he subcomeal or subcpidennal space. Because !he ioju!)' is mild, lhe fluid is relali\'ely prolein poor. A protein-rich exudate results in fibrin accumulalioll. AUlle inflammatory cells, mainly neulrophils. exude<! into a lxxIy cavity or space form a pumlent (suppurative) exudale, Iypically associaled wilh Iiquefactive necrosis. Loss of Ihe epilhelium lcllds to ulccralion. Granulomalous infiammalion is characlerizcd by coileclions of lransfomled mllCrophages called epilhelioid cells.

BP6 44 PBD6 84 24. (O) 'The forrnalion of a fiuid·fjlled cavity afier an infeclion wilh S. clllrellS suggests lhat liquefactive necrosis has occurred. 'llle cavily is fillcd with tissuc debris and


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viable aOO dead neulrophils (i.e., pus). Localized, pus-filled cavities are called abscesses. Sorne bacterial organisms, such as S. al/reus, are more likely to be pyogenic, a- pus fonning. With complete resolurion, the structure of the long remains almosr unaltered. Lung rissue, unlike livet", is no! capable of regenerarion. Searring or fibrosis may fol· low acure inRammation as rhe damaged tissue is rcplaced by fibrous connecrive tissue. Mosr bacterial pneumonias resolve, and progression ro continued chronic inflanunation is uncornmon.

8P6 40-41

PBD6 78-79. 85

25. (E) 1ñe tissue destrucrion rhat accompanies abscess formation as part of acure inflammatory proa:sses occurs fram Iysosomal enzymalic destrucrion, aided by release of reacrive oxygen species. Nitric oxide generared by macrophages aids in destruction of infectious agents. The inrerferon-')' released from Iymphocytes plays a major role in chronic and grallulomatous inflammalory responses. Transfonnillg groWlh faclor-~ fonned by macrophages promoles fibrosis. Proslaglandins produced by endolhelium promore vasodilation.

8P633

PBD664-65

26. (C) Exudation of fluid from venules and capillaries is a key componem of the acute inftammalory process_ 1bere are seveml proposed mechanisms of increase<! vascular permeability. They include formarion of inrerendolhelial gaps by COnlraction of endolhelium. This ¡s caused by mediators such as hisramine and leukotrienes. 1be vessels then become more "leaJcy," and the Ruid leaves thc inrravasctJlar space. Arteriolar vasoconstriction is a lransiem response ro injury lhar diminishes blood loS!>. After neurrophils reach the site of rissue injury outside of rhe vascular space, lhey release Iysosomal enzymes_ P1areleL~ adhere to damaged enclothelium and prol11Ole hemostasis. Lymphatic obstrucrion results in Ihe accumularion of prorein-rich Iymph and tymphocYles, producing a chylous effusioll.

8P627-28

PBD6 53-54

27. (C) TIle paliem has immulloglobulin Jeficieney, which prevenls opsollizatioll and phagocyrosis of mierobes. Defieieney of integrins anJ selecrins and a defeet in microrubules would prevent adhesion and Jocomotioll of neutro-

ACUTE AND CHRONIC INFlAMMATION

17

phils. H20 2 production is pan of the oxygen-dependem killing mechanism. This is inlael in this patienl, because his neurrophils are able ro kili bacteria when immunoglobuJins in normal serum allow phagocytosis.

8P632 PBD6 62-64 28. (O) Prostaglandins are produced through the cyclooxygenase pathway of arachidonic acid melabolism. Aspirin and nonsteroidal anti~inflammarory drugs block the syn-thesis of prostaglandins, which can produce pain. Complement Clq is generated in lhe initial srage of cornplement acrivalion, which can resuU in cell Iysis. LeukOlrienes are generared by the lipooxygenase pathway. which is nol blocked by aspirin. Hisramíne is mainly a vasodilator. Nirric oxide elaborated by endorhelium is a vasodiJator.

BP6 37

PBD6 70-71

29. (C) The formarion of an exudare conraining a significllnl alllOlll1f of protein and cells depends 011 Ihe "Ieakiness" 01" blood vessels. principalJy venules. The extrnva<;cular colloid osmotic pressure increases when exudarion has occurred and the protein conrenl of the exlrnvascuJar space illcreases. The Iympllarics serve ro scavenge exuded Ruid wirh proteill aOO lower the amounr of exlrnvascular aOO extracellular fluid. Sodium and warer relenrion helps dri\'e Imnsudation of Ruid. Leukocyrosis alone is llOI sufficienr for exudation, because the leukocytes musr be driven ro emigratc froro the vessels by chemoractic faeten.

8P626-28 PBD6 52-54

JO. (A) During acure inflammarion, neulrophils extravasale from lhe blood vessels. This process depends on adhesion molecules expressed on lhe neulrophils aOO endothelial cells. In the first Slage of eXlravasation, rhe neutrophils roIl over the endothelium. At this stage, the adhesion berween the neutrophils aOO enclolhelial cells is no! very slrong. Rolling is mediated by binding of selectins ro siaIyated oligosaccharides. The next slep, firm adhesion, is medialed by bincling of integrins on the leukocyres to their receprors inlracellular adhesion moleeule-I or vascular eel1 adhesioll molecule·1 (VCAM-I) on endothelial reUs. Integrills have IWO chaills. a: and ~. A genelic lack of ~ chains prevenls (¡rm adhesioll of leukocYles to endothelial cells. 8P628-29 PBD6 57-59


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CHAPTER

3 Tissue Repair: Cellular Growth, Fibrosis, and Wound Healing PBD6 COOpter 4 - Tissue Repair: Cellular Growth, Fibrosis. and Wound Heoling BP6 Chapter 5 - Repair: Cell Regeneration. Fibrosis. and Wound Heoling

l. 1\eutrali7..ation of transforming growlh facIOl"-/3 (fGF(1) is most likely lO arrea wlúch of lhe fol.lowing steps in Ihe inflammatory·repair response? O (A) Leukocyle exlravasatioo O (B) Increased vascular permeability O (C) Production of collagen O (O) QlelT\()(axis of Iymphocyles O (E) Migrntion of epilhelial cells

2. A 60-year-old femll.le suffered an acule myocanlial ¡nrarction Ihal involved a 3 x 4 cm ¡uea of lhe posterior left venlricular free wall. Creatine kinase was elevaled lo 6<Xl VIL in her serum. She was lrealeo for arrhylhmias ano oecreased cardiac oulpul while in lhe hospital. A monlh later. which of the following palhologic finoings woold yoo mosl expecl to fiOO in her left venlricle? O (A) Absces... O (B) Complete resoIution O (C) CoaguJative necrosis O (O) Nodular regeneration O (E) Fibr"ous sear

3. After viml hepatitis, lhere is usually complele recovery of lhe normal I¡ver archilecture. In contrasl. a healed Iiver abscess caused by bacleria leaves a scar in Ihe liver. Which of lhe following facloes besl explains the difference in oulcome with these IWO differenl forms of liver injury" O O O O O

(A) (B) (C) (O) (E)

18

l1le nalure of lhe etiologic agenl 1ñe exlenl of ¡iver ceII injury The injury lo lhe connective lissue framewOl"k The location of lhe lesion 1ñe extent of damage lo lhe bile duclS

4. A 23-year-old femaJe recciving chronic corticosteroid lherapy for an autoirnrnune disease underv.·enl minor surgery for incision aOO drainage of an abscess on her upper ouler righl armo 1lIe wound healed poorly ovec lhe IleXI month. Which of lhe following aspecl~ of wound healing is mosl likely lo be deficienl? O(A) O(B) O (C) O (O) O (E)

Re-epilhelizalion Fibroblasl growlh faclor elaboration Collagen deposilion Serine prOleinasc produclion Neutrophil infi1tralion

5. A cesarcan seclion was perfamed on a 20-year-old femaJe lO deJi\'eT a lerm baby. and lhe IoweT abdominal incision "'aS sutured. lñc sutures were ren-.,\'ed a week later. Which of lhe foUowing staternenlS rcganIing lhe wouoo site at lhe time of sulure remo"al is most appropriate? OCA) Granulation lissue is still pTesenl O (B) Collagen degradalion exceeds synlhesis O (C) Woolld slrenglh is 80% of normal lissue O (O) There is a predominance of type IV colltlgen O (E) No more wOllno slrenglh will be guille<!

For each of lhe descriplions of lhe wound healing proeess in questiollS 6 aOO 7. match the most c10sely associated lenere<! subslance: (A) CoI.lagenase (B) Cyclin B (Cl EpidennaJ growth factor (O) Fibronectin (E) Integrin (F) Inlerleukin-I (G) P1alelet-derivro growth factor (H) Plasmin (1) Tumor necrosis faclor (J) Type IV collagen (K) Vascular enoolhelial cell growlh faclor (l) Zinc 6. Ouring remodelillg of sears. melalloproteinases degrade extmcellular rnatrix components. This aclion of melaJ1oproc.einases is diminished because of lhe lack of mis substance. ( )


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7. Inlracytopla~mic cytoskelelal elements. including actin. inleracl wilh Ihe extracellular matrix (hrough Ihis molecule lo provide cell atlachmenl and migration in wound healing. ( ) 8. Release of epidennal growth factor in an area of denuded skin causes mitogenic slimulation of Ihe ski n epi(helial cells. Which of Ihe following proleins is involved in Imnsducing (he milogenic signal frum (he epidermal cel1 membrane (o (he nucleus? OCA) O (B) O (C) 0(0) O (E)

G proteins ras proteins Cyclin D cAMP Cyclin-dependenl kina<;e

Ouring grow(h faclor-induced cellular regeneration, which of (hc following tmnsilions during cell cycle is controlled by (he phosphorylalion of Ihe retinoblastoma (Rb) protein:

9.

OCA) G o to G 1 O (B) G 1 to S

O(C) S lO G 2 0(0) G 2 to M O(E) M (oG 1

13. The appeamnce of Ihe Irichrome-stained section of a surgical wound site in Ihe figure is most likely lo be seen how long after sLlrgery"

1 day 2 lo 3 days 4105 days 2 weeks O (E) 1 monlh

OCA) O(B) O(C) O(D)

JO. Which of the following molecules synlhesized by fibmblasts can bind lo cellular integrins and lo eXlracellular collagen and can allach epidennal basal cells 10 ba<>emenl membrane?

14. In a 50-year--old woman tOLllld to be positive for hepatilis A antibody, (he serum asparlate aminolmnsferase (AST) leve! was 275 VIL and Ihat of alanine aminotrallS' ferase (ALT) wa~ 310 VIL. A month later. (hese enzyme levels have relumed lO normal. Al the end 01" (he monlh afler infeclion. in which paJ1 of Ihe cell cycle are mosl of Ihe hepatocyles going (o be?

OCA) O (B) O (C) 0(0) O (E)

OCA) O(B) O(C) O(D) OlE)

Heparin Dermatan sulfate Procollagen Fibronectin Hyaluronic acid

11.

A laceration lo (he left halld of an 18-year-old male was su(ured, alld afler (he sutures were removed a week later, healing conlinued. However, Ihe sile of Ihe wound became disfigured by a prominenl raised, nooular scar lila( developed over (he following 2 months. Whal process occurred? OCA) O (B) O (C) 0(0) O (E)

Organiullion Dehiscence Resolulion Keloid fonnatiOIl Secondary union

12. Ouring Ihe healillg of a skin ulcer, which of (he followinE faClol"S is mosl effective in promoting angiogelle+ sis?

OCA) O (B) O (C) 0(0) O (E)

Platelet-derived grow(h factor (POGF) Epidermal growth faclor (EGF) Basic fibroblast growth faclor (bFGF) Endoslalin Inlerleukin-I

Go G, S G, M

15. A 4()...year--old male underwenl laparolomy for a per· fomteU sigmoid colon diverticulum. A wound infection complicated Ihe posloperative cOUl"Se, and surgical wound dehiscence occurroo. Six weeks later, Ihe wound was only 10% of ¡Is original size. Which of (he following processes best accounls for (he decrease in wound size? OCA) Grea(er syn(hesis of collagen

O (B) Myofibroblasl conlraclion O (C) Inhibilion of metalloproleinases 0(0) Oiminished subcutaneous edema O (E) Elaboralion of adhesive glycoproleills

ANSWERS 1. (e) TGF-13 slimulales many sleps in fibrogenesisfibroblast chemolaxis. procluction of collagen by fibrablasts-while inhibiting degradation of collagen. AI1 olher steps are unaffected by TGF-I3. BP6 51 PBD6 98


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GENERAl PA1HOlOGY

2. (E) The enzyrne elevalion indicale... Ihat rnyocardial necrosis occurred. 1ñe destruction or rnyocardial fibers preeludes complete resolulion. 1ñe area of myocardial necrosis is graduaUy replaced by a fibrOlls scar. Liquefactive necrosis with abscess formalion is J10l a fealure of ischemic myocardial injury. Coagulalive necrosis is l)'Pical fOl" myocardial infarclion, bul after a month a scar will be present. Nodular regeneralion is typical fOl" hepalocyte injury. because hepatocytes are stable cells. BP6 58 PBD6 111

9. (8) Rb proleins control an eXlremely importanl check poiot. lhe G 1 to S IransilÍon during lhe cell cyele. 1be other check poinlS are regulated by a distincl .se! of proleins.

BP6 50 PBD6 96 lO. (D) Fibronectin is a key componenl of lhe eXlracellular matrix. Fibroneclin can be synthesized by monocytes. fibroblasts, an<! endOlhelium.

BP652-53

PBD6 100-103

3. (C) Hepatocytes are slable cells wilh eXlensive abililY to regenerate. However, lhe abilily to restore normal archilecture of an organ such as liver depend.. on lhe viabilily of the supporting connective lissue rrdmeworf,;. If Ihe connective tissue cells are nol injured. hepmocyle regeneration can reslore normal ¡¡ver archileclure. This happens in many cases of viral hepalitis. A liver abscess is associated wilh liquefaclivc necrosis of hepatocyles and Ihe suplX'rting connectivc tissue. It heals by scarring.

11. (O) The healing process may somelimes result in .m exuberanl production of rollagen, giving rise lO a keloid. This tendency may run in families. Organization occurs a<; granulalion lissuc i.<; I'eplaced by fibrous lissue. When a wound pulls apart, dehiscence has occurred. Ir normal tisSlle archilecture is reslOred, Ihen resolulion of inflammalion hilS occurred. Secondary union describes the process by which large wounds fill in 3nd conlrac!.

BP648-49 PBD6 91

BP6 58 PBD6 110

4. (e) Glucocorticoids inhibil wound healing by impair· ¡ng collagen synlhesis. This is a desirable side effect if lile amOllnl of scarring is to be reduced, but results in lhe delayed healing of surgical wounds. Re-epithelizatioo, in part driven by epidennal growth faclor, is nOl affecled by corticosleroid lherapy. Serine proteinases are importanl in wound remodeling. Neutropllil infiltnnion is no! prevented by glucocorticoids.

12. (C) Basic fibroblast growth factor is a polen! indUcef of angiogenesis. It can participate in a11 steps of angiogene· siso Endostatin is an inhibitor of angiogenesis. Platelet· derived growth factor plays a role in vascular remodeling. Epidennal growth factor and interleukin-I have no angiogenic activily. BP6 51 PBD6 104-105

BP6 57 - 58 PBD6 110 5. (A) Al I week, wound healing is slill not complete, aOO more collagen will be synlhcsized in lhe coming weeks. Granulation tissue will slill be present. Wound st:renglh will 10p OUI at aboul 80% by 3 months. Type IV rollagen is found in basement membranes.

BP656-57

PBD6 108-109

6. (L) Zinc is a trace elemelll in Ihe diel Ihal aids wound healing because of its effecl in promoting Ihe aClivilY of melalloproteinases.

BP655 PBD6 106-107 7. (E) 11lIegrins interaet wilh Ihe eXlracellular malrix proleinoS (e.g., fibronectin). Engagement of integrins by exlracellular malrix proleins leads 10 the formalion of focal adhesiOlls where integtins link lO intracellular cytoskeletal elements such as actin. 1ñese interaclions lead lO intrace)luJar signals that modulate cell growth. differentiatioo. aOO migralion during wound healing.

13. (E) This is dense collagen with sorne remainillg di· lale<! blood vessels, typical of lhe final pIlase of wound healillg. By day 1, Ihe wound is filled only wilh fibrin and inflammatory cells. Macrophages and granulation tissue are seen by 2 lo 3 days postoperatively. Neov3SCulari7..ation is mosl prominent on days 4 aOO 5. By lhe second week, collagen is prominenl, and fewer vessels and inflammalory cells are $Un.

BP6 56 PBD6 104,108 14. (A) Hepalocyles are quiescenl (stable) cells that can re·enter the cell cycle and proliferate in response to hepatic injury. 1l1e liver can partially regenerale itself. Acute hepatilis resulls in hepalocyte necrosis, marked by AST and ALT elevalions. After lhe acule process has ende<!, Ihe cells retum lO Go, and Ihe liver becomes quiescenl again.

BP648-49 PBD6 90-91

8. (H) ras proteins tmnscluce signals from gl"O\\1h faetor receptors, such as epidermal growth factor, thal have intrinsic tyrosine kinase activily. G proteins perform a similar function fOl" G-protein-linked, se\'en spanning receptors. cAMP is an effeclor in lhe G-protein signaling palhway. C)'c1ins and cyelin-<!ependent kinases regulale lhe cell cyele in the lIucleus.

15. (8) WOllnd COI1traetion is a characteristic feature of healing by secooo intenlion thal occurs in larger woonds. Collagen synthesis helps fill the defecl bul not contract it 'The inhibition of metalloproteinases leads lO decreased degradation of collagen and impaired conneclivc lis...uc rcmodeling in woooo repair. Edema does diminish over time., bul lhis does not result in much conlJaClion. Adhesive glycoproreins such as fibronectin help lo maintain a cellular scaffolding for growlh and repair bul do nOl conlract.

BP651

BP656 PBD6 108-109

BP652 PBD6 100-101

PBD6 93-94


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CHAPTER

4 Hemodynamic Disorders, Thrombosis, and Shock PB06 Chapter 5 - Hemodynamic Oisorders, Thrombosis, and Shock BP6 Chapter 4 - Hemodynamic Oisorders, Thrombosis, and Shock

1. While shaving one moming, a 23~year-old male nicks his upper lip with the m:1'.Or. Within a second after this injury, blood loss fmm a small dermal arteriole is reduced through Coune.~y

OCA) O (B) O (C) O (D) O (E)

Activated protein C Vasocollstriction Plalelet aggregation Neutrophil chemotaxis Fibrin polymerizalion

2. In which of the following organs is an arterial thmmboembolus least likely lo produce an infarcL? OCA) o(B) O(C) 0(0) O (E)

Brain Liver Kidney Heart Spleen

3. A 21-year-old female sustains multiple injuries. including fractures of (he right femur, righL tibia, and left humeros. 711ese fractures are stabiliud al surgery soon after admissioll lo the hospital. She is in s(able condition. However, 2 days after admission, she suddenly becomes scverely dyspneic. What mosl likely happened to produce her sudden respimtory difficully? O (A) O (B) O (e) O(D) O (E)

Righl hemolhonix Pulmonary edema Fal embolism Cardiac lamponade Pulrnonary infarclion

of Or. J3rnes Cl"3wford, OepanlTlelll of I'athology, Brighllm and Women's Hospilal, SoSlO'L

4. The serum aspartate aminoll'ansferase and a1anine aminotransferase are observed lo be increasing in a 61-year-old man over lhe pasl week. He also has increasing lower leg swelling wiLh grade 2+ piuing edema lo Ihe knees. He has prominenl jugular venous dislention in neck veins lo lhe level of (he mandible. Which of (he following underlying condilions is he most likely to have, based on Lhe gross appearance of Ihe liver seen in Ihe figure? OCA) O (B) O (C) O (O) O (E)

ThrombocyLopenia POItal vein lhrombosis Chronic renal failure Common bile duct obstruclion Congeslive heart failure

5. A 55~year-.{)ld female has had discomfort wilh swelling of her left leg for the pasr week. The leg is slightly difficult (o move, bul there is no pain on palpatioll. A vellOgmm reveals thrombosis of deep left leg veins. Which of Ihe following conditions is most Iikely (o promote lhis evenl? OCA) O (B) O (C) O (D) O (E)

Turbulent blood How Nitric oxide Illgestion of aspirin Hypercalcemia ImmobilizaÜoll

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GENERAl PATHOI..OGY

HislOry for questions Ó lhroogh M: A 56-ycar-old diaoctic malc prl.'SCmed with lcft-sidcd chest pain thal mdiatl.'<1 lo lhe arlll. Serial measuI'Cmcms of scrum crealinc kinao;c isocnz)'me rvlB (CK-MB) kvcl.. revcak'<1 an elevatcd level 24 hours afler the OIlSCI of pain. Coronary angingr,¡pt1y fCvealcd occlusion of lhe lefl anterior dcS(:ending anery.

6.

In Ihis scuing. Ihc musl lil.ely e<lllM.' (lf lhrombosis is

dcrallgcrncnl in whieh of the I"ollowing SICPS in hClIlosla.<;i,. is most likely affectctl in such individuals? 0(1\) Vasoconstriclioll 0(8) PlmdC1 <ldhesion

O(e) PI<lldet aggregaliun OCO) Pmlhrombin !!-cncralion O (El Fibrin polymeriZalion

OíA) Slasis nf blood Hnw O (B) Oamage lo cndothcliullI O (C) Oecrcascd pmdudion of lissue plasminogen aclivalor (l-PA) by intacl cntlQlhcli<11 celh OCO) A dcercascd leve! of antithrolllbin 111 O (E) Mutalion in faclor V genc 7. This pi.lliclll \Yas lhen givcn lhrumbolylic thcrap). Which of Ihe fnllllwing t..!nlg" dit..! he mo."1 likely rcceive? OCA) I-PA O(B) Aspirill O (C) Hepnrin 0(1) Nilric oxide O (E) Vitamin K

8. Afler lhis IrC<lUnenl. the palicnl rcrnaincd slable fur 3 days bot Ihcn rJcveloped sc\'ere brcathlcssness iU"ld \Ya.. diagnnsetl tu havc acule len "entriculilr failure. He dicd 2 hoors luter. Al aulopsy. the lung!<l \Yould mDSl likeJy sho'" which of lhe following hisloJogic chimgcs? OCA) Congcslion uf alveolar capillarie.... wilh fibrin al1(J nculrophils in alveoli O (B) Congcstioll of ah'cular capilliuies ",ith tr,¡nsudale in the ah-coli O(Cl Fibl"Osis of ah'elllar "'¡IU" ,dlh hcan f<lilure cells in ah'I.'Oli 0(0) Mulliplc areas of subpleuml hemorrnagic necro.is O (E) A purulent exudatc in Ihe pleuml space A 27-year-old male is on 11 SCUbil d¡vin~ lrip lO lhe Caribbeall. Afler dcscendin~ lo 50 m in lhe Blue Hole. he rcturns lO Ihe bu'll. AbuUl an hour lalcr. he dc\'elops scvcn:. painful myalgias and arlhr.l!gins. These S)'lIlploms ab'lle ovcr Ihe neXI d.lY. !-lis sYlllploms are 1ll0st likely Ihe result uf

9.

O(A) Dissclllinatcd inlr,lV~ulm' coagulalinll O(B) Sy:o.tcmic vasodilation O (C) Venous thrombosis 0(1) Tissue nilrogcn elllboli O (El Foil globuks in arteriules 10. The len brC"JM of a 39-year-old femOllc is slighlly enlurged eompi.ll"lxl wilh Ihe rigbt. Thc skin o\'crl}'ing thi¡., breasl is thickenetl. R-ddi.~h-ornnge. aOO piucd. MOlmlfloctJ,¡phy rcvea1s <1 km underlyillg dcn!<lity. A linc-necdle a..pirollc 01' Ihi!> ma....<; I"CH"<lls eólrcilloma. How j:o. lhe grn.<;.s appcarance- uf lhe- leli breasl ocsl expli.lined'! OCA) VClIOUS Ihrombosis O(B) Lymphalic OOslm::liun O (C) Ischemia 0(1)) Chrcmic pólssi"c eongcslion O (E) Chronic inllall1lllalion 11. Pmiellls wilh Oln inhcrilc<l deliciency uf von Willcbrand factor tmvc sponlaneous blcl.'tting undcr lhe :-.kin. A

I::!.

A 70--year-uld male is ambulating for toc firsl lime in

3 \\ceks afler hospitalil.ation for a cerebral infarclion. Within minutes of rctuming lO his hospilal room. he has a sudtlen on~el 01" uyspnca. Hc canllol be rc.<¡uscitaloo. Al ilulOpSY. lhe gross appeafi\llce uf Ihe len lung al lhe hilulll ;s depielcd in Ihe figurc. Which 01' lhe following risk fal'IOrs cOllllibutoolhc most lO Ihis 1lnding? OlA) Venous slasis O (8) Pulmonar)' arlcrial mhem.,dcrosis O (C) Lupus anlicoagulanl 0(1)) BronchojJlleulTlonia O (E) Filclor V Leiden llIulation 13. A 25~ycar-old felllille has had lllultiplc episodes of dcep \'enous thrombosis in the pa."1 10 years. She ha.. had one cpisodc uf pulmon111}' Ihromhoemoolisfll. Which of!he folluwing risl. faetors has IHUSl likely cfMltributed lO her condilion'! O(A) faclor V Leiden mutalion 0(8) Alltilhrombin 11I deticiene)' O (C) MUlaliun in protein e 0(1)) HypcrcholcslCrolemia O (E) Smllkin~ 14. A 76-year-old remOlle fell antl fmclurcd her left femoral trochallter. After 2 wecks in Ihe hospital. her len Icg is s\Vollen. l>anicularly her lower leg below lhe kncc. She expcricnccs pain on mu\'ement of Ihis lego and lherc is lenderncss lo palpillion. Which 01' lhe fnllowing eomplicalions i... lllusl likdy 10 uceur afie" Ihl.'se e\'cnts?


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Olapter 4

OCA) Gangrenouli necrosis of the fool O (B) Hemaloma of the Ihigh O (C) Oisseminaled inlravascular coagulation 0(0) Pulmonary thromboembolism O (E) Fal embolism 15. Patients wilh hemophilia A (i.e., factor VIII deficiency) have a bleeding disorder. Bleeding occurli because factor VIII OtA) Acls as a reaclion accelerator (cofactor) during Ihe aclivation of a coagulation factor O (B) Provides the phospholipid necesliary fo.. assembly of coagulation facton;, cofactors, and calcium O (C) Promoles platelet aggregalion O (O) Neulrdlizes antithrombin III O (E) Causes plalelets lo release Ihromboxane A2 16. Within an hour after a gunshol wound lo lhe abdomen, a 16~year-old male begins lo exhibit lachycardia. His skin is l.'ool and c1ammy lo louch. His blood pressure is 80130 mm Hg. Which of Ihe following organ-specific changes would you most expecl to occur over the nexl 2 days atler Ihis injury? O(A) Acule hepalic infarction O (B) Cerebral basal ganglia hemorrhag.e O (e) Renal passive congeslion 0(0) Pulmonary diffuse alveolar damage O (E) Gangrenous necrosili of the lower legs For each of the c1illical histories in queslions 17 and 18. match Ihe mosl closely associaled lellered substance thal plays a role in coagulauon: (A) Adenosine diphosphate (8) Anlithrombin JII (C) EXlracellular matrix (O) Faclor V Leiden (E) Fibrinogen (F) Lupus anticoagulanl (G) Pla~minogen (H) Proslaglandin (1) Thrombomodulin (J) Thromboxane A2 (K) Tissue factor (L) von Willebrand facIor

HEMODYNAMIC DISORDERS

23

20. A 44-year-old male sufrers an acute myocardial 111farction. Arter Ihis evenl, his ejeclion fmction is only 30%. with reduced cardiac output. He develops increasing pulmonaryedema. How does this edema occur? OCA) Lymphalic obslruclion O (B) Oecreaored plasma osmotic pressure O (e) Decrea~ed central venous pressure 0(0) Increased hydroslalic pressure O (E) Acute inAammalion

21. A 70-year-old male with a hislory of diabetes mellitus died of an acute myocardial infarction. The appearance al aUlopsy of his aorta opelled longiludinally is seen in Ihe figure. Which of the tollowing complications of his aonic disease would you most expect to have been presenl during his lite? O (A) Renal infarclion 0(8) Pulmonary thromboembolism

O (C) Edema of lhe left leg O (D) ThromboeYlopenia O (E) Popliteal arterial occlusion

17. A 25-year-old temale presents wilh a slroke resulting from cerebral arterial embolism. In Ihe pasl 3 years she has had an episode of pulmonar}' embolism, and her lasl pregnancy ended in a miscarriage. She is found lo have a falseposilive serologic test for syphilis. ( ) 18. Platelel dense bollies (della granules) relea'iC lhei.. contents, alld plalelel~ aggregale lo form a primary plug wilhin an arterial lumen afier a smal! cut to the forehead in a young boYo 19. Atler a Ihrombus is fomled in an area of va~cular injury, Ihe propagation of Ihe thrombus to normal arteries is prevenled in part by the action of OCA) Tumor necrosis factor 0(8) Plalelel factor 4 O (C) Calcium 0(0) Thrombomodulin O (E) Fibrin

22. A 49-year-old male has congeslive heart failure. He develops pneumollia aflcr a boUI of influenza, and he spellds 2 weeks recupenlling. Laler, he develops pleurilic chesl pain due lO lhe developmenl of tlle lesion depicled in the ligure. Which of lhe following events has mosl likely happened?


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GENERAL PATHOlOGY

O(A) Pulmonar)' infarclion 0(8) Pulrnona')' chronic congcstion

O (C) Puhnunary edema O(D) Pulmona')' acule congestion O (E) Pulmonary \'enous lhrornbosis

r-or each of lhe c1inicaJ hislorie.<; in qucstions 23. 24. 25. aOO 26. malch lhe rn<X'>1 cJosely associawd leucrcd palhologie finding. (A) Air embolus (B) Amnil~ie lluid emholus (q Anasarea (D) Cholesterol embolus (E) Chrouie passivc congestion (f) Fat cmbolus (G) Muml thrombus (H) Organization with recanalization (1) Petechial hemorrhage (J) Phlcbothrombosis (K) Red infaret (L) Saer<ll pitting edema (M) Scptic infaret (N) Vcgetation (O) While infarel

26. A 58-year-old female underwcnt a left ma<;lectomy wilh axillary Iymph node dis.'OCclion fOl' breast caneer. She lhen dcvelopcd marked swelling oC' her left arm Ihat persiste<! for several monlhs. 1be anll was nol lender or erythcmaloos aOO was nol painful lO move 01' louch. She \Vas afcbrile. 1 )

27. A 61-year-old fcbrile female has a blood presSllre of R5/40 mm Hg. Her serum lactic acid level is 6.8 mgldL She RIso ha~ marked peripheral vasodilation. Which of loc lollowing laboratory findings is mosl likely lo be relalcd lO lhe caUSe.' of her c1inieal coodition? O(A) Elevated serum creatine kinase O (B) Decreascd PO:2 011 blood gas ll1easuremenl O (q 8100d eulture POSilivc for Escheric:hill co/i 0(0) Inereased blood urea nilrogen O (E) Deercased hCllmlocril

28. A section lhrough a branch of the righl main polOlOnary ane')' 3t autopsy revcals a band of libroos cOIll](.'<tivc lissue thal extends across thc lumen. Which of the following cvcnlS besl explains loc presence of Ihis finc.ling? O (A) Hemormagc 0(8) Passivc congeSlioo

O (C) Ischemia O(D) l-IypencnsiOll O (E) Thromboembolism

29. Low doses of a~pirin are commonly uscd lO n.x1uee lhe risk of arterial Ihrombosis in palients who ha\'c suffcn.~ rnyocardial infarctiOll. Which une of !he following stcps in hemostasis is inhihilcd by aspirin? O lA) Adhcsion of p1atelels to collagen 0(8) Aggregalion of platelelS

O (q Pnxluctiun of tissuc faclor 0(0) Synlhesis of von Willcbraod factor

O (E) Synthcsis of antilhrolllbin 111

23. The small arte')' depicled in lhe figure is presem in lhe cpicardiulTl of a 58-year-old Olalc wilh severe atherosclcrosis who cxperienced SOlllC anginal pain 2 wccks ago; tocre wa.. no increac;e in lmponin I or CK-M8. ( ) 24. A 6O-)'ear-old female has been hospitalized for 3 wceks aftcr an aulo aceidem in which she sustained fmelures lo the right remur, pelvis. and Icfl humeros. Pl1ysical cxaminatioo reveaIs swelling aOO warrnlh in her left leg, with local pain and tendcmess in her Icft Ihigh. She is othcrv. ise asymptomalic. ( l 25. A hcart lllurmur is ausCtlltatcd in a 73-year-old malc wilh adcnocarcimxna 01' lhe pancrclb. Echocardiogmphy reveals al-cm nodular lesion located on Ihe superior aspect of the amerior milral valve leaRet. Thc valve leallel allpcars to be intacl. The blood culture resull is negalive. ( )

30. Afler falling in Ihe balhlub anJ slriking her hca(l. JI 78-year-old female becomes increasingJy sonmolen\. A day later, a head compuled lomography sean Jemonstrates an accumulalion of fluid benealh lhe dura. compressing the len ccrcbml hemispherc. Whal is Ihe best 'cml lor Ihis Ruid colJection'! O(A) Hematoma O (8) Purpura

O (q Congestion O (D) Pelechia O (E) Ecchymosis 31. A 45-year-old Female is in (lood health. with no medical problems. She takes no mcdicalions. Al thc eOO of an M·hour shift working al her job as a bank teller, she nolices Ihal lhcre is swelling of her lower legs aOO fecl, e\'en lhough lhere was no sweJling al the beginning of thc day. 1ñcre is no pain or erylhema associated Wilh Ihis swelling. Which of Ihe fol!owing meehanisms best cxplains how Ihis phenotllenon occurred?


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OCA) O (B) O (C) O(D) O (E)

Increased hydrostalic pressure lymphatic obstruclioll Secondary aldosteronism Hypoalbuminemia Excessive water intake

32. During routine vaginal delivery of a term infant, a 23-year-old female with an uncomplicated pregnancy develops sudden dyspnea wilh cyanosis and hypotension. She then suffers a generalized seizure, followed by coma. Her condition does not improve over the nexl few days. What is mast Iikely to be present in her periphernl pulmonary arteries? OCA) O (B) O (C) O (D) O (E)

Gas bubbles Thromboemboli Fat globules Aggregates of red blood cells Amniot.ic fluid

ANSWERS l. (8) The initial re.~ponse lO injury is arteriolar vasoconstriction, but Ihis is lransiem, aOO lile coagulation mechanism must be ¡niliato:! lo mainlain hemoslasis. Protein C is involved in anlicoagulalioll to counleracl dOlting. Platelel aggregalion occurs wilh release of faclors such as ADP, but lhis takes several minutes. Neulrophils are nol essenlial lo hemostasis. Fibrin polymerization is part of seconclary hemostasis after the vascular injury is initia1Jy dosed.

BP665-66 PBD6 119

25

4. (E) This is a "I\ulmeg" liver from chronic passive congestiono The enzyme level elevalions suggest thal the process is so severe that hepatic centrilobular necrosis has also occurred. His findings suggest righl heart failure. This regular panern of red labular discoloration is no1 likely lo occur wilh hemorrhage fmm decreased platelels with petechiae aOO ecchymoses. A portal vein Ihrombus diminisbes blood flow lO the liver bul is IlOl likely lo cause necrosis. because Ihere is a dU<lI blood supply. Hepalic congestion is not dire<:tly relaled lO renal failure: lbere is no characteristic gross appearance wilh hepalorenal syndrome. Biliary trael obstruction should produce bile slasis (choleslasis) with icterus.

BP663-64 PBD61l6-1l7 5. (E) 1ñe most importanl aOO Ihe most cornmon cause of venOllS thromOOsis is vascular sta.<;is. Tumulenl blood fiow is another risk for thromOOsis. bul it is more of a faclor in fast nowing arterial circulalioo. Nitric oxide is a vasodilator aOO an inhibitor of plalelel aggregation. Aspirin inhibits plalelel function aOO limits Ihrombosis. Calcium is a cofactor in lhe coagulalion palhway, bul an increase in calcium has minimal effect on the coagulation pnx:ess.

BP669 PBD6 124-125 6. (8) Alherosclerolic damage lo vascular endothelium is lhe mosl commOll cause of arterial thromOOsis. Stasis of blood now is importanl in lhe 10w-pressure venous cireulatioll. Decreased production of I-PA from intaet enclothelial cells may o<:cur with anoxia of the endothelial cells in \'eins wilh sluggish circulation. Decreased levels of anliilirombin and mulation in faclor V gene are inherited causes of hypercoagulability. They are far less COmlTlOIl than 3therosderosis of (:oronary vessels.

BP669 PBD6 2. (8) The 1iver has a dual blood supply, with a hepatic arterial circulatioll and a portal venous circulatioll. Therefore. infaretioll of the liver caused by occlusion of hepalic artery is nol common. Cerebral infarclion typically produces liquefactive necrosis. (nfarels of mosl solid parenchymal Org¡lllS such a~ Ihe kidney, heart, and spleen demonslrale coagulaüve necrosis.

HEMQDVNAM1C DlS()RDERS

124-125

BP676 PBD6 133

7. (A) The lhrombolytie agenl l-PA causes Ihe generalion of pla.~min. which c1eaves fib..in lO disso1ve Ihe doto Aspirin prevents formlllion of new Ihrombi by inhibiting platelet aggregalion. Heparill prevenls lhrombosis by activaling anlilhrombin 111. Nilric oxide is a vasodilator. Vitamin K is required for sYlllhesis of certain c10uing faclor.;.

3. (e) 1ñe mech..'lnism for fal embolism is unknown, particularty the feason why Ihe Ollset of symptoms is delayed from I lo 3 days (or even a week for cerebral symptoms) after the initial injury. The cumulative effect of In.."lny small fal globules filling peripheral ptllmonary arteries is Ihe same as oue large pulmonary thromboembolus. HenlOlhorax and cardiac tamponade should be immediate complications after trnumatic injury, not delayed events. Pulmonary edema severe enoogh lo cause dyspnea shoold not occur because of fiuid S(3lus monitoring in the hospital. Pulmonary infarction may cause dyspnea, bul pulmonary thromboembolus from deep venous thrombosis is Iypically a complication of a longer hospilaJizalion.

8. (8) Acute lerl ventricular fai1ure after a myoca..dial infamion causes vellOUS congestion in lhe pulmonary capiJIary bed and iocrease in h),drostatic pressure, which causes pulmonary edema by transudalion in Ihe alveolar space. Neutrophils aOO fibrin are found in cases of acule infiammation (i.e., pneumonia) of lhe lung. Fibrosis aOO hemosiderin-filled macrophages (heart fdilure cells) are found with long-sLanding. not acule, left ventricular failure. SubpleuraJ hemonhagic necrosis occurs if there are pulmonary thromboemboli. They can cause righl heart failure. Purulenl exuclate in lhe pleural space (empyema) results from bacterial infeclion. not heart failure.

BP674 PBD6 130-131

BP661-64 PBD6113-116

BP665-66 PBD6 118-120


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26

Part I

GENERAL PATHOlOGY

9. (D) He has thc "bends" from dccompression sickncss. Al high pressures durin!l thc deep scuba di ve. nilrogen is dissolved in blood and tissues in large amounts. Ascending too quickly docs nol allow for slow rcleasc of Ihe gas. and sma\l !las blubbles are formC<!. Hemorrhage or thrombosis frolll diSSClllinated intravascular coagulalion is more likc1y lO occur wilh underlying diseases such as sepsis, and recovcry is nol so fast. Syslemic vasodilation is a featurc of SOIllC fomls of shock. Venous thrombosis is more typically a complicalion of slasis, sOlllelhíng thal docs not OCcur in a physically active person. Fat globules in pulmonary artenes are a fcaturc of fat cmbolism, which usually follows Irauma. BP674 PBD6131 10. (B) The caneer spreads to the dermal lymphatics to produce Ihe gross peau d'ornnge appearnnce. 'nlere is an cxtensive venous drainage of lhe brea"t, and canccr or other focal Illass lesions are nol likc1y to cause significam congcstion and cdema of Ihc breast. Ischemia is mre in breasl bccause of thc abundanl arterial supply. Passive con~ gcslion docs not involvc brcast. Chronic infiammalion is rare in breast tissue and not associatcd with caneer. BP6 62 PBD6 115 11. (B) von WiIlebmnd faclor acls a.., a glllc bclwccn plalc1cts and thc exposed extraccllular malrix of Ihe vessc1 wall after vascular injury. None of the olher sleps lislCd hcrc depends on von Willebrand factor. BP665-67 PBD6 llB-120

12. (A) This is a large pulmonary Ihrombocmbolus. The mosl common fÍsk factor is immobilization leading lo ve~ nous stasis. These Ihl"ombi form in Ihc large dccp leg or pelvic vcins, nol in Ihe puhnonary artcries. Coagulupalhics from acquired 01" inheriled disordcrs. such as Ihosc from Ihe lupus anlicoagulalll or factor V mulalion. are possible causcs ror Ihrombosis bul usually are manifestcd at a younger agc and are far Icss common than venous stasis as risks for puhnonary Ihrombocmbolism. Local inflammalion from a pneumonia may rcsult in Ihrombosis of smaU vcssc1s in affecled areas. BP673-74 PBD6130

13. (A) The recuITCnt lhrombolic episooes al such a young age strongly suggesl an inheriled coagulopathy, and the factor V mulalion affeclS 2% lo 15% of lhe populalion. More than onc half of persons wilh a hislory of recurrent deep venous thrombosis have such a defect. Inherited deficiencies of Ihe anlicoagulant proleins anlithrombin 111 and prolein e can causc hypercoagulable slales, but l.hesc are much less common Ihan factor V mulalion. She is unlikely to have caneer al such a young age, bul sorne cancers do c1abomle factors thal promote thrombosis. I-Iypercholcstcrolcmia is a risk factor fOl" alhcTO!>Clemsis thal predisposcs 10 arterial Ihrombosis. BP669-70 PBD6125-126 14. (O) She has decp and superficial venous thrombosis as a conscqucncc of vcnOllS StilSis from immobilization.

Thc largc, dccp thrombi can embolize 10 lhe lungs and Icad to death. Gangrcne occurs from arlerial, nol vcnous, occ1usion in Ihe leg. Vessels wilh Ihrombi Iypically slay inlact; if she had u hematoma il" a conscqucncc of the Irauma from thc [aH, it should be organizing and Jecreasing in size altcr 2 wceks. Disscminated lntmvascular coagulation (DIC) is nol a comll1on complicatíon with Ihrombosis of extremilies or during rccuperation from an injury. Fal cmbolism can occur with fractures, bul pulmonary problcms lypically appear I lo 3 days aftcr Ihc lraumatic cvcnl. BP671-72 PBD6127-129

15. (A) Faclor VIII. tissuc factor, and faclOr V act as cofactors 01" rcaction accclcmtors in Ihc c10uing cascade. Factor VIJI acls as a rcaction accclcrator for !he conversion of faclor X and Xa. '111e plulc1el surrace provides phospholipid for asscmbly of coagulation raclOrs. Platclct aggrcgaLion is promoled by thromboxane A2 and ADP. Thrombox~ anc A2 is rcleased when platelets are aclívated during Ihc process of platclet adhesion. BP6 6B PBD6 121 16. (O) Hc is going inlo shock qllickly afler trauma. Socalled shock lung, with diffusc alveolar damagc. is a common occurrence in lhis situation. The Iivcr is difficult to inrarcl because of its dual blood supply. Basal ganglia hemorrhages are more typical wilh hypcncnsion, nol hypoIcnsion wilh shock. Passivc congcstion is less likely wilh diminished blood volumes and tissue perfusion fmm shock. Gangrene rcquircs much longer lo develop and is nol a cOll1ll1on complication with shock. BP678-79 PBD6136-137

17. (F) 'ibis woman has a hypercoagulable stale, and shc has anlibodics Ihat react wilh cardiolipin, a phospholipid antigen used for lhe serologic diagnosis of syphilis. Thcse so-called alltiphospholipid antibodies are dircctcd againsl phospholipid-protein complcxcs and are sometimes callcd lupus anticoagulant hccausc Ihcy are prCsCnl in saine patients with systemic lupus erythematosus (SLE). J-1owcvcr. lupus anlicoagulant may oecur in pcrsons without any evidencc of SLE. Palicnls with lupus anlicoagulanl have recurrenl arterial and vcnous Ihmmbosis and rcpcatcd miscarriages. In vitro, lhese antibüdies inhibit coagulalion by interfering wílh lhe assembly of phospholipid complexes. In conlrasl, Ihe anlihodics in vivo induce a hypercoagulable slatc by unknown mcchanisms. BPD6 126 BP6 70 18. (A) The adenosinediphosphalc lADP) is rdeased from the dense bodies and is a polcnt slirnulalOr of platelcl aggrcgation. ADP also Slimulatcs ADP rclease fmm olh<?r pliltclets. Thromboxanc A2 , anothcr powerful aggregator of platc1cls. is synthcsizoo by the cyc100xygenasc pathway; il is nol slored in densc bodies. Many other subslanees involved in hemostasis (e.g., fiblinogcn, von WilIebrand faclor, and faclor V) are storcd in thc alpha granules of plalelets. BP667. PBD6120-121


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19. (D) ThrombomO<lulin is presenl on intael endolhelium and btnds Ihrombin. which inhibits coagulation by aetivating protein C. Tumor necrosis factor is nOl significantly involved in coagulaeion. Platelel factor 4 is released from plalelet alpha granules and promOles platelee aggregaeion during lhe coagulation process. Calcium is a oofaetor thae assists c10cting in !he ooagulalion cascade (the elhyIenediamineletraacetic acid [EOTA] in sorne blood colleelion lubes binds cakium lo prevent c1olling). FíOOn protein forros a mesh....'Od:: lhal is essential lo lhrombus formalion.

BP6 66-67 PBD6 119-120 20. (D) 111ere is grealer hydroslatic pressure in the pulmonary capillary bed from his left heart faHure. Plasma oncotic pressure is mainly diminished by decreased synlhesis of prolcin in lhe liver or by loss of protcin lhrough Ihc kidney (prolcinuria). With right heart failurc, there is inercascd celllT'<l1 vcnOllS pressure. Acule inflamlllalioll of Ihe lung (pncumonia) can give rise to :¡Ivcolar eXlldalc. This occun; only if infcclion supervencs, It is nol cause<! by a myocardial failure,

BP662-64 PBD6114-117 21. (E) A mural Ihrombus fills an alherosclcrolic aol1ic aneurysm below lhe fCnal artcnes. Onc of lhe complications of mural Ihrombosis is cmbolization whcn a small ptccc break!> off. 1ñc cmbolus is carricd distally and may occlude lhe poplileal artery. Becau~ this thrombus is in me arterial circulation, an embolus will not go lo thc lungs. A vcnous Ihrombus produces leg swclling from edema. Although platclets contribute 10 lhe fonnalion of thrombi. the plalclel eount docs nol drop appreciably with fonnalion of a localizcd thl'Ombus, and a gcncralizcd proccss such as disscminaloo intT'dvascular coagulalion (Dlq is necded 10 use up enough platelets to cause thrombocylopenia

BP671-72

PBD6127-129

22. (A) 111is is a hcmorrhagie infarel bascd 011 Ihe pleurJ., Iypieal of what may happcll whcn a mcdium·si:rJ:d Ihrombocmbolus 1000gcs in a pulmonary artcry branch. Thc infarel is hClllorrhagic bccause Ihc bronchial artcrial circulation in the lung, which is from Ihe systcmic arterial circulalion and is separatc from the pulmonary anerial circulation, conlinues to supply a small amounl of blood to che affcetcd arca of infan:tion. Passivc congestion, whclhcr acutc or chronic, is a diffuse proccss. as is cdema., which docs flOl impart a red color. Pulmonary \'cnous thrombosis is rore.

BP6 75 PBD6 132-133

BP671-73 PBD6127-129 ,

27

24. (J) Vcnous slaSis favors the development of phlebolhrombosis (venous thrombosis) particularly in lhe leg veins and the ¡xlvic \'eillS_ The OOslruction may produce local pain and swelling, allhough it may be asymptomatic. Such deep Ihrombi in large veins creatc a risk for pulmonary Ihromboembolism.

BP672-73 PBD6 129 25. (N) A thrombotic mass that fonns on a cardiac val\'e is known as a \'cgelation. Sudl vegetations may produce thromboemboJi. Vegetations on the righl·sided beart vah'es may embolize lO the lungs; those on lhe len embolize s)'Slemically lO Of"g3ns such as brain. spleen, and kidney. A "paradoxical embolus" occun; when a right-sided cardiac lhrombus crosses a patent foramen ovale an<! enters Ihc systemic artcrial circulation. Persons wilh C'dllccr may have a hypercoagulable statc (frousscau syndromc) that favors Ihe developmclll of artcrial und vcnous Ihrombosis.

PBD6 127 26. (L) Thc surgcry disruplcd lymphalic relurn, resuitillg in funClional Iymphalic obstruclion alld Iymphedcma of Ihe armo The Iymphatic channcls are important in scavenging fluid and prOlcin thal have Icakcd illto the tissues from lhe intrdvasctJlar space. Allhough lhe amOllnl of fluid thae is drainoo through I)'mphatics is nol grea!, it can gradually build up over time.

BP6 62

PBD6 115

27. (q She has scplic shock, with poor lissue pcrfusioll evitlcnccd by lhe high Iacealc Icve!' Vasodilation is a fealure of scplic shock, typically from gram-negati\'C cndotoxcmia. An elcvaloo creatinc kinase Ic\'el suggcsts an acutc myocardial infarclion, wt1ich produces cardiogcnic shock. A decreased POz suggcsls a problem wilh lung vcmilalion or perfusion. An incrcased blood urea nitrogen conccntration is a fcalure of renal failurc, not the cause of renal faiJure. A dccreased hemalocrit suggesls hypovolemic shock from blood loss.

BP6 77 PBD6 134 28, (E) Organization wilh rccanalizalion OCClln; in a vcsscl after Ihrombosis or thrombocmbolism. A small fibrous band may be alJ thal relllains. Hcmorrhage alone cannol resull in fibrosis. Passive oongcstion of surrounding lung tissue has a negligiblc cffecl on arteries. Ischemia oould resull froro lhe same lhrombocmbolus bul would produce a hemorrllagic infarct of Ihe lung. Pulmonary hypertension oould occur from !he decreascd vasctJlar bcd resulting from rccurrcnt. widespread thrombocmbolism lo small pcriphcral pulmonary arteries_

BP671 23. (H) Thcrc is an organlZlflg Ihrombus in Ihis small artcry wilh scvcra! small rccanalizcd channcls. Such a periJ*lcral ancrial occlusion was not suffieicnl lo pnxlocc infarction, as evidenccd by lhe ¡ack of enzymc c1cvation. -nlJ'ombi Ixxomc organizcd ovcr lime if Ihcy are nol dissolved by ñbrinolylic aclivity.

HEMODYNAM1C OISORDERS

PBD6127-12B

29. (8) Aspirin blocks thc c)'c1ooxygcnasc pathway of arncllidonic acid melabolism ane! gencro:ltion of cieosanoids. including thromboxanc Az, which causes vasoconstriction and promotes plalc!el aggregalion, Platelcl adhcsion to cxtraecllular matrix is mcdialed by inleraelions with von WilIcbnllld faelor. Tissue factor (Ihromboplaslin) is releascd


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GENERAl.. PATHOLOGY

with tissuc injury and is not plalclcL depcndent. Endothclial cells produce von WiJJcbrand fOClOr indepcndcnl of plalclct action. Antilhrombin In has llluicoagulanl propcrtics bccaLL..c il inactivatcs scvcrdl coagulalion faclors, bUI ilS funetion is 001 affcetcd by aspirin.

BP637.66-67 PBD671.120-122 30. (A) Shc h<ts a subdural hem<ltoma. A hematoma is a cOllcclion of blood in a polcmial spacc or wilhin tissltc. Purpura denotes blotchy hcmorrhagc 011 skin, serosal, or muoou... membrdllC surfaces, and arcas largcr Lhan I lO 2 an are oflcn call ecchymoses. Pclechiac are pinpoinl are<l$ of hemonhagc. Congcstion occurs whcn therc is vascular dilatiou with pooling of blood within an organ.

BP664 PBD6117-1IB 31. (A) 1bc hydroslalie prcssure cxcrtcd from starnJing leads 10 edema in dependenL parts of the body. Lymphatie obstruction from ¡nfcetion or tumor- can Icad to Iymphc-

<!cma, bul this is a chronic proccss. Sccondary aldoslcronism results frolll congestivc hcal1 failurc alld rellal hypopcrfusion, bU! Ihis is a gcncra1i:-..c<l proccss. I-Iypoalbu+ mincmia Icads 10 more gcncrdlizcd ~cma a.. well. allhough the cffecl is rtlOf"C pronounced in dependent arcas. If shc is hcalthy, normal renal funclion is sufficicnt lO c1car free walcr from oro:Ll ínlal:c.

BP661-62 PBD6114-115 32. (E) AmniOlic Iluid cmbolism is a rare cvcnl in prcg~ nancy but carnes a high mortalilY mlC. 1ñc fluid rcachc:s torn ulerinc veins lhrough r\lptured fclal mcmbrdJlCS. Gas bubbles in \'csscls from ajr cmoolísm can be a tare cvcnt with somc obslctric procedurcs. bul it is nO( likely with natuml dclivcrics. Pcriphcrdl pulmonary thrombocmboli are mosl likcly lO produce chronic pulmonary hypertcnsion and dcvclop ovcr wccks lO months. Fal globulcs are sccn with fal cmoolislll, usually after scvcre trauma.

BP674-75 PBD6131-132


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CHAPTER

5 Genetic Disorders 8P6 Chapter 7 - Genetic and Pediatric Diseases P8D6 Chapter 6 - Genetic Disorders

l. An amence of low-dcnsily Iipoprolein (LOL) rcccplOrs on liver cclls, inherited as an autosomal dominant condilion, is besl chamcterized by which of Ihe following laboralory lesl findings in a 22-year-old male who has had a myoc¡¡rdial infarclion: OCA) Abelalipoproteinemia O (B) Hypcrtriglyceridemia O (e) Ketonuria

(M) Muscle phosphorylase (N) Spcctrin (O) Sphingomyclinase 3. Maje childrcn over scveral generations in a family have been affected by a progressive disorder involving multiple organ syslems. Thesc childrcn have had coarse facial featurcs, corneal c1ouding, joinl sliffness, hepatosplenomegaly, and mental rclardation. LabomlOry lesling rcveals increased urinary excrclion of mucopolysaccharides. Thc accumulaled mucopolysaccharidcs are found in macrophages ("balloon cclls" filled with minule vacuoles) on bone marrow biopsy. Some of lhe childrcn al autopsy have had subcndolhelial coronary arterial deposils Ihal produccd myocardial infarclion. ( )

O(D) Hypoglycemia O <E) Hyperc1lOleslero1cmia 2. A 25-year~old maJe ha.. a work-up for inferlilily and is found lO have oligospcrmia. Physical examinalion findings inelude bilateral gynecomastia_ reduced testicular size. and rcduced body hair. Karyolypic analysis will mosl likcly rcveal which of lhe folJowing abnommlities?

4. An apparenlly heallhy 25-year-old female drops out of her aerobic exercise dass because of severc musde cmmps during cvery session for lhe pasl 2 rnonlhs. Seveml hours after each of lhese scssions, she has nOliced lhal her urine has a brown color. ( 1

OCA) 46,X,i(Xq¡ o(B) 47,XYY OCe) 47,XXY

0(0) 46XXJ47XX,+21 O (E) 46.XY.dcl(22qll) For Ihe descriplions of a patienl with a genelic disease in questions 3, 4, and 5, sclecl lhe mosl doscly associaled letlercd gene product lhal is likely 10 be abnonnal or abscnl with Ihal disea'>C: (A) Adenosine deaminasc (B) Alpha,~antitrypsin (e) Alpha-L-iduronidasc (O) Oyslrophin CE) Factor VLII (n Fi bri lIi n (G) Globin ehains (H) Glucocercbrosidase (1) Glucose-6-phospbatase (J) Hexosaminidase (K) Homogentisic oxidase (L) Lysosomal acid maltase

Courtesy of Dr. Tmcc Worrcll. DcpartnlCnt of Palhology. Uni\'crnily of TC}¡i\l¡ SouthwClltcrn Mcdicul Ccntcr. DlIlla~, TX.

5. A 6-momh-old infant has failure to Ihrive. with muscle weakncss and enlargement of liver and spleen. A chcst

29


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GENERAL PATHOLOGV

radiograph reveals markecl cartliomeg.aly. The chilcl clies wilh congeslivc heart failure al 19 monlhs 01' age. At aulOpsy, the myocartlial fibers ancl liver cclls are sccn microscopically lO have thc appcarance shown in lhe fig~ ure. ( ) 6. MullifaclOrial inherilanCC is mosl likely lO playa signif+ icam role in the appcarancc 01' O(A) O (B) O (e) (O) (E)

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Marfan synclromc Tay-Sachs cliscase El)'throblaslOsis fetalis Cleft lip Polyeystic kidneys

for each of the palienls wilh genelic clisorclcrs in questions 7 and 8, malch ยกhe mosl chamcterislic cause of dealh from the lisl: (A) (B) (O (O) (E) (F) (G) (H) (1) (J)

(K) (L)

Acule leukemia Aortic disseelion Bronchieetasis Chronic renal failuTc Hean failure causcd by Ihick.ness ol' coronary artery cndothelillm and valve leaAcls I-Iean failure caused by myocartlial glycogen aecumulalion Inlraccrebral hemorrhage Malignanl transfonnalion of a sulJcutancous tumor Myocartlial infarclion Pneufllocystis ca,-iniยก pneumonia Scvcrc cliarrhea and livcr failure Scvere congenital hemt rnalformation

7. An inranl born lO a 36-year-old molher was obscn'ed al binh lO have microccphaly, a clcft lip and palalc, and six fingers on each hand. ( ) 8. An othcrwise normal 12-year-olcl female with fauy dcposits lInder the skin li.e., xanlhomas) of her clbows collapscd suddenly while playing volleyball. ( ) 9. A IO-year-old male, although mentally retarded, is able lO carry out aClivities 01' claily living, including feeding and dressing hirnself. On physical examination, he ha.. brachyccphaly and oblique palpcbral fissures with prominel1l epicanlhal folds. On lhe palm of each hand is seen a 1l"aIlSverse crease. On auscultation of the chest, there is a grade IIIIVI syslolic murmuro Which of Ihe following cliseases will he mosl likcly have by Ihe age of 20? O (A) ACUle leukemia O (B) Hepalic cirrhosis O (O Chmnic renal failurc 0(1) Acutc myocartlial infaretion O (E) Aonic disscclion 10. The lcfl hand of a baby bom al 38 wccks' gestation has the appcardnce shown in Ihe figure. Which of Ihc following chromosomal abnormalities is mosl likcly to be prcsent?

11. A young man's ophlhalmologist rcfers him to a neu+ rologist becausc. in adclilion lO failing eyesiglll. he complains 01' progrcssive muscle weakness. The neurologisl lakes a careful hislOry and finds tIlat several of this young man's malc and female relalives are similarly affecled. His mOlher, her brother and siSler, and twa 01' his aunt's children are affccled, bllt his unde's children seem to be fine. His genclic disordcr is an cxample af O O O O O

(A) (B) (C) (D) (E)

TrinucleOlide rcpcal expansioll Genelic imprinting X-linked inhcrilancc paUern A mitochondrial mUlalion Uniparental disomy

12. Which of Ihe fol1owing karyOlypic abnormalitics in a Iiveborn baby is most likcly 10 be l"ound in a parenl? OCA) O (B) O (C) O (D) O (E)

Robertsonian translocation Ring chromosome lsochromosome Paraccnlric IIlvcrsion A q arm delelion

for cach of Ihe dinical histories in qucslions 13 and 14, malch Ihe mosl dosely associaled lcttcred karyolypc; (A) 46,XX

(8) 47,XX,+IS (e) 45.X/46,XX (O) 47.XYY (E) 47.XY,+13 (F) 47,XXY (G) (1-1) (1) (J)

23,X

47,XXX 46,X,X(fra) 46,XY,der(14;21)(qlO:ql0),+21 (K) 47.XX,+21 (l) 4?XY.+16

OCA) 45,X 0(8) 47,XX,+21

O(e) 47.XY,+18 0(0) 69XXY O(E) 47,XXY

13. A 25-ycar-old female wilh amenorrhea is 146 cm lal! alld is found on physical examination 10 have a webbed neck. An abdominal magnelic rcsonance scan shows "streak ovarics" Ihat are small. long, and thin. (


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14. A 25-year-old male. a professional hockey player who has never won Ihe Lady Byng Irophy. is 195 cm tall. Therc are no abnormal findings on a physical examinalion, other than sorne prominent facial 'lene scars and sorne missing leelh. I-Ie is nmrricd and has IWO childrcn who show normal developmenl for age. ( )

GENETIC DISORDERS

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31

18. A fclus is most likcly 10 be can-ied to lerm wilh whieh 01" !he following chromosomal abnommlities? OCA) Triploidy 0(8) Monosomy O (C) Ancuploidy

0(0) Telraploidy O (E) Mosaicism 19. A b<lby born al lerm has llillbiguous extem<ll genitalia. The parents Wllilt to know the baby's sex, bUI Ihe physician is hesitanl lO assign a sex withoul funher information. A chromosome analysis is pcrformed. and Ihe karyolype is 46.XX. An abdominal computed lomography (O) scan reveals bilalerally enlarged adrenal glands, and Ihe inlernal genilalia appear lO consist of ulerus. lubes, amI ov'lries. This is mosl likcly to be an example of

Courtcsy of Dr. Mauhcw Fries. Dcpartmcnt uf Palhology. IJni\"CI'<ity of Texas $oothwestcrn Medical Cenle~. f>dllas. TX.

OCA) Female pseudohemmphroditism O (B) Testiculllr femininizalion O (e) A nondisjunctional evenl wilh loss of a Y chromosome 0(0) Exccssive IrinucleOlide repcals O (E) Milochondrial DNA l11ulalion

20. 15. A Io-year-old neurologically normal child has hepatosplcnomegaJy along with anemia and leukopenia. Abone marrow biopsy is pcrfonned and shows al high magnifiea~ OOn Ihe flndings depicled in Ihe figuTC. Therapy for Ihis condition can be accomplishcd by infusion of OCA) O (B) O (e) 0(0) O (E)

Glucocerebrosidase Acid malta"e Glucose-6-phosphalID:iC SphingomyelinlLSC I-Iexosaminidase A

16. Mental relardation hao;ยก arfecled sever<ll generations of a ramily. Only male ramily membcrs manifeSI Ihis condilion. In general, il appears that the severity of menlal relardation has inercascd wilh each passing gcneralion. By which of Ihe following mechanisms is Ihis genetic eondi!ion mosl likely lO be produccd? OCA) TrinucleOlidc repeal mulalion O (B) Frameshift mutation O (e) Missense mulalion 0(1) Poinl mulalion O (E) Milochondrial DNA l1lulalion 17. About a do:t,.Cn pale brawn maeules avcraging 2 to 5 cm in diameter and having inegular borders are observcd on lhe Irunk and exlremilies of a 15-year-old female. Examinalion of her eyes wilh a slit lamp rcveals pigmented nodules in Ihe iris. Other family members llTC similarly affeeted. Which of Ihe following neoplasms is she mosl likcly lO develop? OCA) O (E) O (e) 0(0) O (E)

Dcrmatollbroma Lciomyoma Neurofibroma Lipoma I-Iemangioma

A !-year-old female is broughl to allention because of failure to lhrive, mental relardalion, and poor motor funclion. Examination of Ihe 1'Clina reveals a cherry red spol in Ihe macula. Both parent<; and a brolher and sisler are normal. However, one brolher dicd, with a similar eondition, <lt Ihe age of 18 months. This genetic disorder mosl likcly resulled fram wllich of lhe following underlying abnormalilies? OCA) O (B) O (C) O (J) O (E)

Mulation MUlalion MUlalion MUlalion Gcnomic

in a mitochondlial gene in a gene encodjng a lysosomal enzylTIe in a gene cncoding a receplOr prolein in a gene encoding a slructunlJ protein irnprinting

21. A IO-year-old maJe prcsents with recurrenl infCClions. PhysicaJ cX<lmination rcveals a cleft palalc and murmur suggeslivc of eongenital Ileart discase. A Ihoracic cr sean reveals a srnaller Ihan normal Ihymus. ResullS of l<lbonltory invesligalions suggest mild hypoparathyroidism. Whieh of Ihe following leSls is mosl likely lO be hclpful in <lrriving al the diagnosis? O(A) Human irmnunadefieiency virus (HIV) Iype I RNA level O (B) Fluorescence in .~itll hybridization (F1SH) analysis wilh a probe for chromosome 22q II O (C) Polymera.~c chain l'Cacrion (PCR) analysis for Irinuc1eOlide repcats affeeting the X chromosomc 0(1) Assay for Ihe enzymc adenosinc deamina"C in Iymphocyres O (E) Lymph nade biopsy 22. A 2-year-old child demonstmtes failure lO thrive. Hepatomegaly and eeehymoscs of the ski n are round on physical examination. Thl: child exhibils eonvulsions, and Ihe blood glucose is found tO be on!y 31 mgldL. Liver biopsy shows cclls filie<! wilh clcar vacuoles Ihal slain


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GENERAL PATHOLOGY

positively for glycogen. Which of the following conditions besl expl<lins lhese findings? OCA) McArdle syndrome 0(8) von Gierl.:e di"C¡¡.<;e

O (e) Tay-Sachs dise¡¡'''e 0(0) Hurler syndrome O (E) Pompe discasc 23. An 8-year-old femalc can bcnd her lhumb back to touch her foreann. Shc can pull her skin OUI fram hcr abdomen about 8 cm, and a l"ul lO her ski n gapcs opcn and is difficull to repair. Her underlying diseasc process results from an inhcrilcd defcct in OCA) O (B) O (e) 0(0) O (E)

Alphal-antilrypsin Relinoblastoma (Rb) protein LOL reccptor Collagen Faclor VIII

O (e) Thc rdlc of synthesis of collagen 0(0) TI1e level of glueose-6-phosphalasc in liver cells O (E) TI1e leve! of (lt-antilrypsin in Ihe liver 26. A fctus is dclivercd stillbom at 19 wceks' gestation. Thc maccrdted fetus shows marked hydrops fetalis_ Therc is a large poslerior cystic hygroma of lhe necl.:. AUlopsy reveals internaJ anomalies, including aorlie coarctation and a horscshoe kidney. Which of Ihe following I.:aryotypcs is most likely to be found on chromusome analysis of felal cells?

OCA) 47.XX.+18

Om) 48.XXXY O(C) 47,XX,+21 0(0) 47,XVY O (E) 45,X 27. A 13-year-old Illale has becn drinking large quantilies of flltids and has an insatiable appelite. even for ft Iccnager. However. he is 10sing weight am..! ha" bccome more lired and lisllcss ovcr the past monlh. A complete blood count is normal, bul he is found to havc a fa..ting scrum glucosc of 175 mgldL. A diagnosis of lype I diabeles is made. What is lhe probablc inhcrilance pattern of his underlyillg discase? OCA) 0(8) O (e) 0(0) O (E)

Aulosomal dominanl MullifacloriaJ X~linkcd rcccssivc Milochondrial ONA AULOsomal recessive

28. A prcgnant woman wilh a I"amily history of fragile X syndromc wants prenatal diagnosis of her felUs. Amplifieation of the appropriate region of Ihe FMR/ gene by PCR is auemplcd on ONA from amniOlic fluid cells, but no ampli~ fied producls are obtained. What is lhe besl next step? COllrtesy of Dr_ Vijay Took. Departrncm of Pmhology. Uni,'cn;ity of

TelGls SOllthwcslem Medical Cenlcr. I)dlla.<. TX.

24. An ultmsound examinalion pcrfonned al 18 wccks re"cals lhat this maje felUs is mildly growlh retarded. Mltltiplc congcnital anomalics are observed. induding a vcntricltlar scptal dcfecl, alrial seplal defccl, horseshoc kidney, and omphaloccle. An anmiocenlesis is pelfonned. and lhe fctal cells are examined wilh F1SH. Ba<;e<\ on lhe lindings shown in lhe figure. the tllOst likcly bryotypie abnommlilY is

OCA) 46,XY,dcr{ 14;21 )(q lO;q 10),+21 O tB) 47,XY,+ 18 O (e¡ 47,XXY O (D) 46,XY,del(22q 11) O (E) 45,X/46,XX 25. A 4-year-old child dCmOnslrdtcs scvcrc ncuml0!:1ic delcrioration. Examinalion reveals marked hcpalosplcnomegaly, <Uld abone marrow biopsy shows nUlllerom¡ t"oamy vacltolatcd macrophages. Which of lhe following tests is likely to reveal Ihe diagnosis of Ihis eondition? OCA) The nUlllber of LDL receptors on hcpatocyles O (B) Thc leve! of sphingomyclina..;c in splcnie macrophagcs

O(A) Routinc karyotype of the amniotic fluid cells O (B) Routine karyotype of lhe unalfecle<\ falher O (C) Southern blol of lhe DNA from Ihe alllniolic fluid cells 0(0) PCR analysis of Ihe mOlhcr's FMRl ~cne O (E) No furlher lests ncccssary

29. A 3-year-old child with developmental delay, ataxia, scizurcs, and inapproprialc laltghter has a noonal karyolypc (46,XY), bul ONA analysis shows Iha! he has inheriteJ bOlh ol' his number 15 chromosomcs from his father. His genelie disonJer is an examplc of OlA) O (B) O te) O (O) O (E)

X-linkcd inherilance pattel"ll Malernal inhcrilance patlel"ll Mulalion of milochondrial ONA Gcnclic imprinting Trinudeotide repcat cxpilllsiun

30. A 34-year-old malc has 10ss of vision from a subluxation 01' Ihe crystallinc Iens ol' the righl eye. A mid-syslOlic c1ick is audible On auscltltation of lhe chest, and an echocardiogídm reveals a floppy mitml valve. 111e aOltic arch is also dilated. His brolher and his cousin are also affeclcd. Which ol' lhe following genes is prubably involved in his underlying discm¡e process?


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O(A) Oystrophin 0(8) Collagen O(C) Fibrillin

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ANSWERS

GENETlC DISORDERS

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33

6. (O) Cleft lip and mosl congenilal malformations are nol determine<! by a single gene, and they may be conditioned by environmen!al influences (multifaclOrial inherilance). Marran syndromc is an autosomal dominant disordcr affccling fibrillin. Tay-Sachs diseasc, a Iysosornal sloragc disonler, is inherited as an aulosomal reccssive lrait. Erylhroblastosis fetalis results from malemal sensitiza!ion to fetal red blood cells and fornllltion of anlibody that can cross lhe placenta in fulure pregnaocies 10 produce hcmolysis. Polycyslic kk1ncys may be caused by dominanl, rccessive, or sporadic mutations.

BP6 190 PBD6 165 l. (E) Familial hypcrcholeslerolemia rcsulls froro mulalions in lhc LDl receptor genc such lhat lOL cholcstcrol is increascd in lhc blood bccausc il is not catalxllizcd or lakcn up by the liver. Triglyccridcs are l'IOl primariJy affcetcd. KelOnuria can occur wilh slan'ation or insulin deficiency. lbe LDl rcttptors do not playa direcl role in g1uconcogencsis.

BP6IB2-183 PBDO 150-153 2. (C) He has Klinefcltcr syndrome. one of lhe more common chromosomal abnormalilics, which occuo; in aboul I of 850 li\'Cbom males. lbe findings can be subtle. 11Ic 46,X,i(Xq) is a varianl of Tumcr SyndroOk (seen only in females), eaused by a dcfcclive secood X chromosome. 1lle 47,XYV karyOlype is not uncommon-aboul I in 1000 livebom malcs-and is associatcd with lalleT lhan average slaturc. A pcrson wilh a mosaic such as 46.XXI 47.XX.+21 has milder fealures of Down syndrome than persons wilh lhc more lypical 47,XX.+21 karyolype.1Ăąe 22q 1I dcletion syndromc is associatcd wilh congenilal defccls afTccting lhe palalc, facc, and heart. and in sonle cases, T-ccH immunodcficiency.

BP6196 PBD6174 3. (C) This is Hunter syndrome, one of lhe mucopolysaccharidoses (MPS) Ihal rcsult from deficiencies of Iysosomal enzymes. such as a-L-iduronidase. 111e glycosaminoglycans lhal accumulale in MPS include dermalan sulfllte, heparan sulfale, keralan sulfllle, and chondroitin sulfllle. AII of lhe MPS varianlS me 1tllIOSOlllal rccessive. except for Hunter syndrome, which is an X-linked reccssive.

BP61B7-188 PBD6159-16O 4. (1\'1) Shc has McArdle syndrome, a form of glycogen stordge discasc with an onsct in young adulthood and in which there is a deficicncy of musclc phosphorylasc enzymc. As a consequcnce, glycogen accumulatcs in skeletal muscle. Bccause strcllUOllS exercisc rcquires glycogcnolysis and use of anaerobic melabolism. muscle cramps ensue and lhe blood laClale levcl docs not risco Myoglobinuria is seen in abool one half of cases.

BP6188-189 PBDO 160.163 5. (L) This is Pompc diseasc, a form of glycogen slornge diseasc lhat rcsulls from a dcficiency in Iysosomal glucosi<!ase (acid mallase). The glycogen slored in Ihc myocardium results in massive cardiomegaly aOO hcart failure wilhin 2 ycars.

BP6188-189 PBDO 160.163

7. (L) Clcft Iip aOO palate, along wilh miCl'OCCphaly and poIydaclyly. are feal.Ures of trisomy 13. These paticnts a1so ha\'e SCVCf"C hcart dcfccls.

BP6 194 PBD6172 8. (1) This palien! has homozygous familial hypercholesterolemia, cha.racterizcd by scvcrc hypcrcholesterolemia !hat gives risc tO xanlhomas and prcmalure coronary artery diseasc lcading 10 myocardial infarction.

BP6182-183

PBDO 151-152

9. (A) He has Down s)'tldrome, or trisomy 21. This is one of the trisomics lhat can resull in a livebom baby. Howcver, thcrc are oflen many associatcd congenital anOIllalies, particular1y congenilal heart disease, including ventricular seplal defecl. These are happy cbildren who can function fairly wcll. However. lhere is a lO- lO 2O-fold incrcased risk for acule leukemia. I.f pcrsons with Oown syndrome live lO the age of 40, virtually a1l of them will have evidence for Al7hcimer discasc. Hepalic cirrhosis is a feature of galactosemia. Chronic renal failurc may be scen wilh genetic disorders Ihal produce polycystic kidneys. Myocardial infarelion al a young age suggcsts familial bypercholeslerolelllia. Aortic dissection is sccn in pcrsons with Marfan syndrome.

BP6 193-195 PBD6 170-172 10. (8) There is a single palmar flexion crease and a single nexion crease on lhe fifth digil. These are fealures of lrisomy 21. Monosomy X may be rnarked by a shon fouJ'lh metacarpal. Wilh IriSOlllY 18, lhe fingers are often c1enched, wilh digils 2 and 5 overlapping 3 and 4. Triploidy may be markcd by syndaclyly of digil'i 3 and 4. There are no chameterislic features of the hand of a male with Klincfeller syndrome.

BP6193-194

PBD6170-172

11. (D) This is a c1assic pullern of malernal inheri!ance, rcsulting from a mulalion in mitochondrial ONA. Males and females are affccted, bul affcctcd males cannOl tmnsmit lhc t1iscasc lO Ihcir offspnng. Bccause milocbondrial ONA encodcs many enzymes in volved in oxidalive pbosphorylation. mutalions in milochondrial genes exert Ihcir mosl deleterious effccts on organs most dependenl on oxidative phosphorylalion, including the central ncr"ous system (CNS) and Illuscles.

8P6178 P8D06179-180 12. (A) Nearly all of the normal genctic malerial is present in lhe case of a robertsonian lranslocation, because only a small amount of p arm from cach chromosome is losI.. Statistically, onc of six feluses in a mother who car-


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GENEAAL PATHOL03Y

ries a roberlsonian translocalion will also be a carnero In balanced reeiprocal tmnslocalion, the same ¡xJssibilily of inheriting Ihe dcfcct exists. Howevcr, olhcr stnlClural abnOrmalilies are likcly 10 result in loss of significant genelic materiaL rcducing survivability, or lO interfere wilh meioSIS. BP6 192-193 PBD6 16B-170 13. (C) The fcatures are Ihose of classic Tumer syndrome. Paticnts who grow lO adullhood are usually mosaies, karyolYPC of 45,X/46,XX. BP6196-197 PBD6174-176 14. (D) The extra Y chromosome is seen in aooul 1 of 1000 liveoorn males. nlere is a tendency for such persOns lO be tall and prone lO scvere acne. The missing teelh are spccific to hockey, not 10 an cxtra Y chromosomc. There is a COnlTovcrsy aboul whclher such individuals exhibil more aggressivc behavior. Howevcr, Ihe behavior of virlua!ly all 46,XYY males is indistinguishable from Ihat of olher males. BP6196 PBD6174 15. (A) Gaucher disease has three forms. Type 1 accounts for 99% of cases and does nol involve lhe CNS, as in Ihis child. 11 is caused by a dcficicncy of glucocerebrosidase, and infusion wilh Ihis enzyme reduces severity and progression. Typc 2 involves the CNS and is lelhal in infancy. Typc 3 also involves Ihe CNS, allhough nol as scvcrely as lypc 2. A dcficiency of acid mallase is a fcalurc of Pompe disease. VOn Gierkc discase rcsults frolll deficiency of glucose-6-phosphatase. Sphingomyclinese deficiency leads lo Niemann-Pick disease Iypcs A and B. Typc A, Ihe more common form, is associalcd wilh severc neurologic delerioralion. Typc B, Ihe less common form, may rcscmble this case, bul lhc appcarance of macrophages is differcnl: Ihcy contain many small vacuoles. In Tay~ Sachs discase. there is a deficiency of hexosaminidase A. It is also a~sociated wilh scverc menlal relardalion and dealh before 10 ycars of age. BP6 187 PBD6 158-159 16. (A) This is fragile X syndrome, a condition in which Ihcrc are 250 to 4000 tandem repeats of Ihe Irinuc1eotide scquencc CGG. In general, lhe more repcals, Ihe worsc is Ihe diseasc or Ihe earlier the onset in conditions causcd by lrinudeotide repcals. The Irinuc1eolides are dynamic; because Iheir size incrcascs during oogcnesis. Ihe male off~ spring have more severe diseasc comparcd wilh, for exampie, Iheir gmndfalhers. Wilh a fmmeshift mUlalion, one, IwO, or Ihree nuc1eOlide base pairs <lfe inserlcd or delcted. The prolein lranscribcd is abnonnal. A misscnse mUlalion results from a single nuc1cotide base subslitution, resulting in an abnonlml protein being elaborated. Abnormalilics of milOChondrial ONA alC IransmiUed on the malernal side. BP6176-178 PBD6 143, 177-178 17. (e) She has neurofibrOlllalosis typc l. Neurofibromas are mosl l1umerous in Ihe demlis bul may occur in visceral orgallS as wd!. Dcrmalofibromas are 'liso subcutaneous ma"ses, but lhey are lypically small and solitalY and 1101 seen with neurofibromatosis. Leiomyomas are mosl fre-

quent in the ulerus and alC nOI Iypically par! of a genetic disorder. Lipoma" can oceur jusI aboul anywherc bUI are sporadie in OCCUITCncc. Hcmangiomas may occur sporadically On the skin. They are nOI pan of neurofibromalOsis Iype l. BP6189-19O PBD6162-164 18. (E) There are a grcaler numbcr of potcntially normal cells having Ihe propcr chromosomal eomplcmenl wilh 1ll0saicism. and this may allow babies wilh abnoTlllalilies of chrOlllosome number lO make il lO term and beyond. Trip" loid fctuses rarely go past Ihe secolld trimeSler and are vinually never livebom. Likewise, lctraploidy aceounls for lllany firsl-Irimesler fetal losses and is nol survivable. Loss or a chromosome is devaslaling; Ihe only monosomy in which Ihere is possible survival 10 term is Turner syndrome (mollosomy X). Most aneuploid conditions (Irisomies and monosomies) lead 10 fetal demise. Trisomy 21 is the mosl likely 10 go lO lenn. BP6 191 PBD6 16B 19. (A) lt is impoTlanl 10 be careful in assigning sex; changing your opinion of the sex is abOut as popular as an umpire changing Ihe callo True hermaphoditism, with ovarian and Icsliculm lissue prcsenl, is rare. This palient has female pseudohermaphroditism. resulting rrom exposure of Ihe felUs lO exccssive androgenic stimulation, as can occur wilh congenilal adrenal hypcrplasia. Both Ihe gonadal and karyotypic sex is remale. Male pscudohennaphroclilism has a variety of forms. bUI Ihe mosl common is testicular fcminizalion Ihat rcsulls from androgen insclIsitivilY, al1d Ihe affecled pcrsons are phenolypically femalcs bUI have lestes and a 46.XY karyotypc. Nondisjunclional cvents lead tO monosomies or trisomies. Trinucleotide repcats are .'iccn wilh fídgile X syndrome in males. Abnormalities of l11itochondrial DNA have a malernal tmnsmission paltern and do nOl involve sex chromosomes or sexual chamCleristics. PBD6 176 (B) This palienl secms lO have a .'icvcrc inheriled neurologic disease Ihal gives rise to a cherry red spol in Ihc retina. nle pallern of inheritancc (e.g.. nomlal parcnts, an affecled sib) is consiSlenl wilh autosomal recessive in~ heritance. This is most likely Tay~Sachs disease, causcd by mulalions in lhe gene lhal encocles a Iysomal enzyme hexosamindase A. Mulalions in genes affecling receptor pro~ teins and slructural proteins Iypically give rise 10 an aulosomal dominant patlern of inhcrilancc. MilOChondrial gcnes have a malernal patlelll of Iransmission. Genomic imprinling is characterized by a parenl of origin efTecl. BP6186 PBD6 148, 155-156, 179, and 180 20.

21. (8) This patient has an immunocleficiency chaídcterized by infection and a small lhymus, congenital malforma~ liollS, and hypoparalhyroidism. This cluster is characleriSlic of lhe 22q 11 dclction syndromc, readily diagnosed by FISH. HIV infcction can lead to acquircd immunoclcficiency syndrome, bul lhere are no congenilal anomalies associaled witll Ihis condition. Trinucleotide repcals of Ihe X chromosome are seen wilh Ihe fragile X syndrome, which maniresL" with mental rctardation in males. Adenosine deamina"e deficiency can also cause imnlllnodefi~


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ciency, bul il is nol ussociated wilh congenital mal formalions. A Iymph node biopsy may show a reduction in T or B cells associatt:d wilh various forms of immunodeficieocy, but this is nol a specific ICSI lO help confinn a spccific diagnosis.

PBD6173 22. (B) This paliem has von Gierke disease. Bccause of lhe dcficieocy of gluoosc-6-phosphalase. glycogen is nol. melabolizcd rcadily lO glucose; and lhe patients have severe hypoglycemia, leading lo convulsions. Imracyloplasmic accumulalions of glycogcn occur mainly in ¡iver aOO kidney. Another forro of glycogen storage disease. McArdle syndrome. rcsults from a deficiency of muscle phospllorylasc and lc-dds 10 muscle cramping. TayoSachs disease is charnclerizc<! by a deficienc.y in hexosaminidasc A aOO rcsulls in sevcre ncurologic dcterioralion. In Hurler syndrome, lhe enzymc o·L-iduronidasc is dcficicnt. Affected children have skelctal deformities and buildup of mucopolysaccharidcs in cndocardium and ooronary aneries. leading lO hcart failure. Cardiomegaly aOO heart failure mm Pompe disease. anolher form of glycogen storage diseasc.

GENETIC DISORDERS

35

26. (E) These are findings of Turncr syndrome. Thc hygroma is quite suggcslive. Such affccced babies are rarely li"chorn. Turner syndrome accounts for a considerable portion of fi",l lrimester losscs. Trisomy 18 can be marked by multiple anomalics as well, but overlapping fingers and a short neck are more Iypical features. Additional X chromosornes may not bave a seriollS cffcet. because all bul one X ehromosome is inactive. Down syndrome (47.XX,+21) may be accompanied by a hygroma aOO hydrops, but venlricular scptal defeet is more frequent lhan coaraalion, and horseshoe kidney is UTlCornmon. 47,XXY does ool resull in stillbirth. lbcse males have no oongenilal dcfects.

BP6196-197

PBD6 174-176

27. (8) He has Iypc I diabelCS mellitus, which has an incrcascd frequcnc.y in some familics. but the ex.aet mechanism for inhcritance is unknown. TIte risk is abolIl 6% foc offspring when first-ordcr rclalives are affeeted. HLAlinked genes aOO Olher genclic loo alang with environmcnIal faetors are eonsidered importanL This pancm of inhcritanee is multifaetorial.

BP6 190,564-565 PBD6 165,915-916

BP6188-IB9 PBD6160-I63 23. (D) Shc ~ Ehlcrs-Danlos syOOrome. which results from a collagen defcet lhal makes conncclive tissues weak aOO fragile. A deficicncy of o,-anlilrypsin lcads to liver and lung di.sease. A mulated Rb prolein is associatcd wilh dc,'clopmenl of rclinoblastoma and osteosarcoma. Lnherited dcfccts in thc numbcr of LDL receptors resull in early and advanccd alhcrosdcrosis. A deficienc.y of factor VIIl occurs io hemophili a A.

BP61B2 24.

PBD6149-150

(8) 'Thc baby ha.. findings associaled wilh lrisomy

18. In Ihe FISH analysis. the chromosollles in each cell have becn paintcd wilh a markcr lO chromosome 18, and therc are Ihree markers pcr cell, consislent wilh a Irisomy. In rcalily. many eells would have lO be counled lo allow for artifacls in prcparution. Trisomy 18 results from Ilondisjunctional cvcnls in 1110S1 cascs. MOsl trisomy 18 cases are stillborn, and survival beyond 4 rnonths is rare.

BP6194

PBD6172

25. (B) Thc clinieal fealurcs of Ihis child-neurologic invol"cmcnl. hcpalosplenomegaly. and accumulation of foamy macrophages-suggesl a lysosomal stordgc disordCL Onc such disordcr. with which lhe dinical hislOry is quile compatible. is Nicmann·Pick disease Iype A. It is characterizcd by Iysosomal accumulalion of sphingomyelin duc lO a scvere deficiency of sphingomyclinase. Reduced numbcrs of LDL TCecpton; on hcpalocytcs can be sccn Wilh familia! hypcrcholcslerolemia. Collagcn synthcsis is im· paired with Ehlcrs-D·dnlos syndrome. 1ñc glycogen stcrdgc diseasc known as von Gicrl.:c disease rcsults from glucosc· 6-phosphalase deficienc.y. Globules of o.-amilrypsin are seen in livCT cclls wilh inhcrilcd dcficicnc.y of o.-anlitrypsin.

BP6 186-1B7 PBD6 156-158

28. (C) Failure lo find amplifit:d product by PCR in such a case could mean that lhe fcll.1S is not arrecled ()I" lbal thcre is a full mutation that is 100 large lO be picked up by PCR. Thc ncxt logical slep is a Soulhcrn blol. analysis of genomic DNA from fetal cells. ROUline karyotype of lhe amniotic fluid cells is much less sensitive than a Southem bloL Km)'olype of the unalTcaed father cannot provide information on thc slalUs of the FMRI gene in lile felus. bccausc amplification of Ihe trinudcotidc occurs during 00gCl1csis. For the same rcason, PCR of molher's FMRI gene is of 110 value.

PBD6 183-184, Fig. 6-36 29. (D) Thcse are features of Angclman syndrome. The DNA analysis shows ulliparental disomy. Thc Angelm¡lll gcnc encoded on ehromosome 15 is subjeet lO genomic imprinting. 1I is silcnccd on Ihe palernal chromosomc 15 bUI is aClive 011 Ihe maternal chrolllosome 15. Ir Ihe child lacks malemal chromosome 15. thcre is no active Angclman gcne in Ihe somalic cells. This gives rise lO the abnormalilies Iypieal of Ihis diSOl'der. Thc same effecl occurs when thcrc is a delelion of the Angelrnan gene from the matermtl chromesome 15.

BP6199 PBD6180-181

30. (C) Hc has Marfan syndrome, an aulosomal dominant condition that is eauscd by quantilative and qualitative defeets in fibrillin fram mUlations in lhe fibrillin gene. Genelic mutations in lhe dyslrophin gene are involved in Duchenne aOO Bccker muscular dyslrophies. An abnormal coLlagcn gene can aCCQunl for osleogcncsis imperfecta and Ehlers-O'".mlos syndromc. 1ñe NFI protcio is abnormal in neurofibromalosis lype 1. Disordcred spectrin lcads lO hcreditary spherocytosis.

BP6 181

PBD6 148-149


.. I>ot for salel > .. lIe AIIA I1POJldlD< I >

CHAPTER

6 Diseases of Immunity HIV ís mosl JikeJy calJsed by a mula/ion affccling which of the 1"0Uowing genes?

PBD6 Chapter 7 - Diseases of Immunity BP6 Chapter 5 - Disorders 01 the Immune System

l. A 25-year-old fernale has pancylopenia. proleinuria, alld a false-posi!íve serologic lest for syphilis. A ches! radiograph revcah; bilateral pleural cffusions. A friction rub is auscullaled over lhe chest. Which of the following historical findings is mosl likc1y?

O (A) Photosensilivily O (B) Urclhritis O (C) E..·.;ophagcal dysmolility O (D) Xerostomia O (E) Congcnital hearl discase

O (A) T-cc11 receptor O (8) Chemokine receplor O (C) Intcrleukin-2 receplor O ~D) CD28 receplor O (E) Fc receplor 4. A 20-year-old fema1e has an crylhemillous rash over her I"ace on both chccks alld across the bridge 01" hcr no$C. This msh is made worse by sunlighl exposure when she is ouldvors. Along wilh Ihe rash, she has had musclc and joinl pains for severa! molllhs. However. radiographs 01" lhe joints do not show any abnvrmalities. and she has nonnal joinl mobility without deformity. Which 01" Ihe following laboratvry tesl findings is most characteristic of the discase?

O (A) Elevatcd anti·strcplolysin O (ASO) titer O (8) I-ILA-B27 genotypc (C) MarkL>dly dccrcased sefllm levd of immunoglobuJin

2. A 30-year-old female prescnt<; with fever, anhritis, and rash. She also has a history 01" recurrenl thrombosis and infcclions. Inilial laboralory investigmions reveal that antinuclear antibodies are positivc at 1:1600 and that antidoubk-",lml"ldoo DNt\. 3.\\ti.boóies afe posi.ti.vc al \"."3'200. Thc scrum crcatininc level is markcdly e1evaled. and levels of scrum complemcnl are decrcascd. A VDRL lesl for syphi\is is positive, and in vi\ro \esls fOl coagu\afion (proIhmmbin time and partial Ihromboplastin lime) are prolongcd. Which of lhe following c1inical features is most like\y causcd by antibodies thal inlelÍere wilh the coagula¡ion lesl?

O

O (A) Arthritis

O (e) Penicillin O (D) Glucocorticoids O (E) Melhotrexale

O (8) Rccurrenl Ihrombosis

O (C) Rash O tD) Renal failme O (E) Fever 3. In epidemi%gic studies of human immunooeficicncy virus (HIV) infeclion and acquiroo immunodeficiency syndrome (AIDS), il was noliccd Ihal certain individuals failed lo devclop HIV infectiolJ despile knowlJ eXpDSure lo Ihe virus under condilion.<; that causcd HIV diseasc in all olher individuals similarly cxposcd. When Ihe C04+ Iymphocyles frOI11 resistanl individuals are íncubillcd wilh HIV-I, Ihe)' fail lo be infectcd. Such a resislance lo infcclion by

36

G (lgG)

O (D) lnereascd rheumatoid factor titer O (E) Antibodies to double-slrandcd ONA 5. A /5-year-o/d female has !he sudden onscl of difficuhy brcalhing within minutes alter a bce sting. She also manifests marked urticaria, and lhere is marked edema of the hand that was stung. Which of lhe following pharmacologic agenls is besl for Ircating these signs and symptoms?

O tA> Cydosponnc O (B) Epinephrine

For each of the c1inical histories in questions 6 and 7, match lhe most doscly associated immunolvgically rnediatcd pathologic process that can occur in the anccted palÍenls: (A) Angiocdema of skin (O) 8ronchoconstrictioll (O Cerebral Iymphoma (O) Conlact dermatitis (E) Hemolytic anemia (F) Keratoconjunetivitis


< llOt for salel > < lIe .llJIA npo_ I >

Chapler 6

(G) L.ocali:led amyloidosis of lhyroid (H) Pam!hyroid hypoplasia (1) Sacroiliitis (1) Sclerodaclyly 6. A 31-year-old female has a positive antinuclear anti~ body test with a titer of 1:2048 and a diffusc hOlllogeneous staining paUern. When she is outside in the sun for more Ihan an hour, she devclops a rnsh ovcr her face. A urinaly) sis reveals pmtcinuria. (

DISEASES OF IMMUNITY

37

ing lesls is lTIosl specific for the diagnosis of tilis condition?

o O O O O

(A) Anli-double-slrandcd DNA anlibodics (B) Rhellmatoid factor Ialex test (C) Anti-UI-ribonucleoprotein antilxx\ics (O) Antihistone anlibodies (E) Anti-Jo-I antibodies

7. A 28-year-old female has had scvcre pwriasis involving Ihe skin of her face. trunk. and extremitics. She is found by serologic testing lo be positive for HLA-B27. She has been diagnosed with uvcitis. Her antinuclear antibody and rheumatoid factor tests are negative. ( ) 8. A 48-year-old maJe has a tOlal white blood cell (WBC) count 01' 6900/p.L. wilh a differential COllnt of 72 segmenlcd neUlrophils. 3 band neutrophils, 18 Iymphocytes. and 7 monocytcs. Scrum immunoglobulin levcls show 1.9 gldL IgG. 0.3 gldL IgM, and O.UI gldL IgA. His antinuclear antibody test rL."Sull is negalive. His skin test rcsult 1'01' mllmps and Candida anlígcns is positive. Which of !he following infcclious agcnts is mosl Iikely lo produce an il1ness in Ihis palient?

Counesy of Dr. l-Ielrnul

Renkl~.

DepanmeJll of Pmhology, Bri(!.hllm lIJld

WorncJI's HO<ll'ilal. B,,,;lon. MA.

O (A) Pncwllocyslis carjnú

O (B)

Slrefll(lCOcCII.~ pnewl10niae

O (C) Hepalitis B virus O (D) Aspergiflus jfal'us O (E) HerpL."S simplcx

A 37-year-old male known to be HIV positive has n01iced Ihe appcamnce of multiplc, 0.5- 10 1.2-cll1. plaquelike. reddish purple skin Icsions on his face. trunk. and extremilies. Some of Ihe larger lesions appc3r to be nodu· lar. Thesc Icsions have appcarcd over lhe pasl 6 mon!hs and have slowly enlarged. Molecular analysis 01' !he spindie cells found in the Icsion is likely lo rcveal the geTlOlIlc of which of Ihe following vinlscs'!

9.

O O O O

(A) (B) (C) (O)

Cytomegalovirus Epstein-Barr virus Adenovirus Human herpcsvirus-8

O (E) HIV·I

10. Ouring Ihe induction of immedime (Iypc 1) hypcrscnsilivity responsc. which 01' !he following cel/s sccreles CY4 IOkines that stimulate IgE production by B cells, promotes mast cell growth, aOO rccruits and activaws eosinophils?

O (A) CD4+ Iymphocytes O (B) Natural killer (NK) cells O (C) Macrophagcs

O (O) Dendrilic cells O (E) Neulrophils 11. A 52-year-old female prescnts with dilTuse pain 1Il her thighs and shoulders bilatemlly. difficulty in rising frum a chair and c1imbing slcps. and a rash wilh a violaccous color around Ihe orbits and on the knuckles. Antinuclear anlibodies are posilive at 1:160. Which of Ihe follow-

12. A renal biopsy is pcrformed on a 31-year-old female who presellls wilh increasing edema, chesl pain, and a rash rol' lhe past 6 months. She has an increasing scrum crcatjnine level, and proteinuria wi!h red blood cell casts is found on urinalysis. The light microscopic appearancc of the renal biopsy is sccn in Ihe figure. It is staincd with perjodic acid-Schiff stain. Which of !he lollowing antibodics, if present, is diagnoslic 01' this condilion1 O (A) Sd-70

O (B) Anti-Sm O (C) Jo-I O (O) Anlí- HLA-B27

O (E) AllIi-centromere 13. Larvae of Trichinella spirulis are present wi.thin Ihe skelelal musele fibcrs of !he diaphragm of a 23-year-old male. He has a fever and pcriphcral blood cosinophilia. Years latero a chest radiograph shows only a few small ca!cificalions in Ihe diaphragm. Which of ¡he following iml1lunologic mechanisms probably conlributcd to Ihe destruclion of Ihe larvae'!

O O O O O

lA) (B) (C) (D) (E)

Antibody-depcndcnt cel1ular cytotoxicity lADCC) ComplcmenHncdiatcd cell Iysis Fommtion of Langhans giant cclls Absccss /onllation wilh neutrophils Synlhesis 01' leukotriene C 4 in masl cclls

14. A 45-year-old maJe rcceived a kidncy from his brother 42 months ago. For the first thrcc years, he did wcll wilh Ihe allograft, with minor episcxJcs of rejcction Ihat were controlled. However. he has had increasing renal failurc for the past 6 monms. He is afebrile. A urinalysis spccimen examined microscopically shows no WBCs. A computed tomography sean of Ihe pelvis shows mat Ihe


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38

""l.. !

> .. 11.. AIIA IIPOJliil<K ! >

Part 1

GENERAL PATHOLOGY

allograft is rcduccd in size. Which of lhe following immunologie pnx;esSL'S is pmbably happcning in lhis Irdnsplalllcd kidney? O (A) Macrophage-mediated cell Iysis

Vascular inlimal fibrosis O (C) Granulomalous vasculilis O (O) Rclea<;c of IcukOlricne C 4 fmm mast cells O (E) Complcmcnl-mcdialed cell Iysis

O (B)

15. A young malc wal\(.<; inlo an dcvator full of pcoplc who are coughing and sneezing. all of whom appcar lo have colds or Ihe 1111. The inl1uenza viral particles Ihal he inhales atlach lo respiralory epilhclium, and viral Iransformatlon reduces the dass I major hislocompatibilily complcx (MHe) molccules on lhese epilhelial cdls. Which of Ihe following cells Ihen rc.spond:- lO dcslroy Ihe infeclCd cells?

O O O O

(A) NK cell (B) Neulrophil (e) Macrophage (O) C04 cell O (E) Dcndritic cell 16. A 35-year-old male has a history of mild infeclions of lhe uppcr rcspiralory lract. He also has had diarrhea for mosl of his life, although /lot severc enough lo have malabsorption Wilh weighl loss. Aflcr an cpisodc of trauma with blood loss. he rcccivcs a blood lransfusion cornplicated by an anaphylaclic reaclion. Which of Ihe following undcrlying condilions best explains lhcse findings?

O O O O O

(Al (B) (C) (O) (E)

Severc combincd immuncxlcfieicncy HIV infcction DiGeorge syndrome Wiskotl-Aldrich syndrOlne Scleclive IgA dcficiency

17. A labormory worker who was known lO be "allergic" lo fungal sporL"S was accidentally exposcd lo cullure of lhe incriminating fungus on a Fliday aflernoon. Wilhin 60 minules, he devclopcd oouls of sncczing, walering of eyes, and nasal discharge. He decided lo tnkc lhe day off, and the symptoms scemed to subside in a few hours. However, Ihe next morning, while he was still at hOlJ1e, his sYIllPloms rcappcared, although lhe laboralory funglls was not prescnt in his environmelll. His symp!oms pcrsisted thmugh lhe weekend. aOO he wenl lO su: a doctor on Monday morning. If lhe physician examines a nasal discharge llndcr Ihe Illicroscopc, which of Ihe following eells are likely lO be seen?

O O O O O

(A) (8) (e) (O) (E)

18.

Masl cells and neulrophils Lymphocyles and macrophagt::s Neulrophils. oosinophils. ¡¡nd CD4+ Iymphocytcs Neulrophils and C08+ lymphCX:Yles Masl cells, Iymphcx:ytes, and macrophagl.'S

A 30-year-old malc known lo be infectcd wilh H1V lO have difficu1ty wilh activities of daily living. Hc has Tllemory pmblcrns and "dccrcased abililY to perfonn funclions Ihat rcquire finc molor control, such as wriling or painting. His C04 Iymphcx:yre cotlnl is 150/J.lL. Which of hegin.~

Ihe following ccll lypcs is mosl irnpol1am for the disscmination of lhe infcclion into Ihe cenlml ncrvOllS system? O (A) NK cell O (13) Mal.Tophagc

O (C) Neutrophil O (O)

cm:

Iymphcx:yle

O (E) langerhans cell

19. A vasculitis affex;ts ¡¡rteries in many visceral organs of a 29~year-old maleo There is focal fibrinoid necrosis of lhe small arterial and arteriolar vascular media along wilh inlravascular lIlicrOlhrombi. Sealtered neutmphils are .~een in lhese areas of necrosis. Whieh of Ihc following laoomlory tesl findings would you most expccl for this palienl? O (A) Incrca~cd IgE O (8) Nelllropcnia

O (e) Dcereascd C3 eomplelllellt

O (O) Tubcrculin skin test positivily O (E) C04 Iymphcx:ytosis

20. A 63-year.old male with ehronic rhcumatoid arthtitis pm,ents wilh proleinuria and thc nephrolic syndrome. A reclal biopsy is pcrformcd. which demonstrates alllyloid deposilion. Amyloid depositioll in Ihis sening

O (A) Is wilhin Ihe cyloplasm O (B) Contains mainly (>50%) P componelll

O (C) Is derived fmm an acule.phasc reaelant (SAA) O (O) Docs nol show bircflingence aftcr Congo red stain~ ing O (E) Is derived fmm lambda Iight ehains For each of lhe c1inical historil.'S in queslions 21 and 22, malch the mosl c10sely associalcd 1cllered immunologically medialed disease pn.lCl.'Ss: (A) (8) (C) (O) (E) (F) (G) (H) (1)

Ankylosing spondylitis Dcrmalomyosilis Oiffusc systemic sclerosis Oiscoid lupus erythemalosus Juvenile rhcumatoid anhrilis limited scleroocrma Mixed conncclive lissue discase Polymyositis Reiter syndmme (1) Rheumatoid ar1hritis (K) Sjogrcn syndrome (l) Syslemic lupus erythematoslls (SLE)

21. A 41-year-old rnale has xeroslomia, myalgias, rashes over his faee, and arthralgias. An anlinudem alllilxxly lesl rcsult is posilive wilh a spccklcd pattem. He also has high lilen; of anlibodies lo U1 rirnmuclcoprolein. He has no evidence of renal discase. ( ) 22. A 42-year-old female is oothered by tightening of Ihe skin of her fingers, making lhem difficult lO hendo Shc has increasing diffieuUy swallowing, and hcr fingen; bccome cyanolic and painful on exposure to cold. An x-ray film of the cheSI shows prominenl interstitial markings, and lung


« not rOl' . .lel :> « Ke .Il/IA

npoJl<fDl I

:>

Coopte¡ 6

funclioll tests reveal moderatcly sc"crc rcstricli"c pulmonary discasc. Labomlory lcsling rc"cals a posili,,·c DNA lopoisomcrasc I antibodl' test. ( ) 23. A 3-llIonlh-old bol' prcscntcd with recurrenl infcctions. Thc illfcetiollS agenls includcd Candida albiams, P. can"njj. Psel«1omonas aemgjnosa. .100 cylomegalovirus.. Dcspilc inlcnsivc treatmcnl wilh anlibiolics .100 anlifungal drugs.. he dicd al the agc of 5 monlhs. Al aUlopsl'. Iymph nodcs werc fouOO lo be Slllall wilh \'Cf)' fcw Il'mphocl'les .100 llO gcnninal ccnlclS. 1lJc thYlllus was hl'poplastic. a<; were lhe Pc)'cr palchcs .100 tonsils. 1llcre is a history of oIhcr males in the famill' who prcscnlcd in a similar manncr. Thc mosl common calL<;C for this forlll of immunodcficicncy is

D1SEASES OF IMMUNITY

39

O (A) Malfornlation 01" lhird and foorth pharyngeal pouches O (B) Failure of malUmlion of B cclls inlo plasma cells O (C) Lack of adcninc dcaminasc O (O) Acquisilion of malernal HIV infcclion al delivcry O (E) Failurc of differentimion of prc-B cclls inlo B cclls

O (A) Maternal HIV infcctiOIl

O (B) Loss of chromosOIllc 22q II O (C) Mutation in Ihe cOlllmon 'Y chain of cYlOkinc rcceplors

O (O) MUL1tion in Ihe Brulon tyrosine IUnasc (blk) gene O CE) Mutation in CD40 Iigand 24. A 34-ycar-old fcma\e has cxpcricnccd increasing muscular weakncss over scvcral months. This weakrcss is most pronounccd in muscles thal are uscd repclilively, sud¡ as the Icvalor palpcbrae of Ihc cyclids. 1lJc lnosl lilrell' mechanism (or muscle weakncss in Ihis case is

O (A) Sccretion of cytokincs by activatcd macropl1ages O (B) Lysis of llIusclc cells by C08+ T cclls O (C) Antibody-mcdiatcd dysfunction of ncUl1)lIluscular junction O (O) Dcposition of immWlC complcxes in the llIusde capi liarles O CE) A dclal'cd hyperscnsitivitl' rcaclion againsl musdc anligcns 25. A 45~l'car-old fcmale has cxpcricllccd difficulty in swallowing Ihat has incrC<lscd in scverity over the pa<;t year. Shc has also expcricnced malabsorplion, demollstrmed by a lO-kg weight loss in lhe ¡>ast 6 Illomhs. She rcports inCrc.1sing dyspnea. Echocardiography dClTlonslralcs a largc pcricardial clTusion. Hcr antinuclear anlibodl' test is positive al 1:512 wilh a nudcolar pattt..Tn. Which of the following scriollS complicalions of hcr undcrll'ing autoimmune discasc is most likcly lO occur?

O (A) O (B) O (e) O (D) O (E)

Mcning.ilis Glomcruloncphritis Pcrformcd duodenal ulccr Adrcnal failure Malignanl hypcrtensioo

26. Soon after binh. a felnalc nconatc dcvclopcd letany rrom hypocalccmia. Within the ncxt year. this ¡nfanl had bouts of P. carillii pncwnonia. Aspergillfls /l/migallu pncumonia. alld pardinAucnza virus aOO hi..'1'pCS simplcx virus upper respirdlory inf(:ctions. Which of Ihc foUowing mechanisrns is n:sponsiblc for Ihe c1inical fcatures sccn in this case?

Counesy o( Dr. Traa: WOCTell, DcpanI1lCflI of l"alhology. Uni"cNly of TUlU Soolhweslem Medial ScOOoI. Dalias. TX.

27. A 39-year-old fcmalc has fingcrs mal are tapercd and clawlikc. with dccrcascd mol ion a! the smaU joints. T1le microscopic appearance of lhe skin is shown in lhe figure. She also has diffuse intcrstitial fibrosis of lhe lungs, with pulmonary hyperten.~ion aOO COI' pulmonalc. Whid¡ of lhe following oc'flTlal inflarnmatory cclls is considered thc n1051 likcly inilialor of thc proccss thal results in her skin disease? O (A) CD4 Iymphocytc O (B) Mocrophagc O (C) Mast ccll O (O) Ncutrophil O (E) NK ccll

28. A 19·year-old fcmalc prCSCnll,.'(j wilh fever, myalgia. sorc throm, and mild crylhematous rash over her abdomen and thighs. Thesc symptoms abatOO in a 1Il0mh, aOO she rcmaincd hcalthy unlil 8 l'cars laler, Whcll decreased visual ,1cuitl' and pain in hcr right cl'c loo lO a finding of cyto-mcgalo\'irus rclillilis on fuOOuscopy. Assuming that her inilial illncss aOO thc ocular problcm arc a part of lhe same discasc proccss, whid¡ of the following laboratory lesl findings is lnosl likell' lo be found in Ihis palienl añcr hcr ocular problcms began to appcar?

O (A) Antinuclear antibody lilcr of 1: 1024 O (B) Total scrUIll globulin Ic\'c1 of 650 mgldL O (C) Posi!Í\'c H.LA-B27 anligcn O (O) Anlirenlromere anlibody liter of 1:512 O (E) CD4 lymphocylC rounl of 1000¡.tL 29. A 32-ycar-old femalc wilh a ID-year hislOf)' of inlravcnous drug use dcvelopcd a chronic wa((.'I)' diarrhea. Exmnination of the stool rcvcalcd CYSIS of CryptosporidilUll pan'lIt1l. Shc Ihcn dcvclopcd a cryptococcal meningitis that


«

t>CIt

for &a1.. 1

40

> « ....

Part 1

IlJlR tTPOJl,<UD< I

>

GENERAL PATHOlOGY

wa.. succcssfully trc<llcd. A diagnosis of oral candidiasis was madc a rnonlh laler. Which of lhc following neoplasms is shc al grcalcst risk fOl' devcloping?

following immunologic 1ll1.:chanisllls has Ihis renal damage occurrcd?

O (A) Non-Hodgkin lympholl1a

O (A) Anlibody-dcpcndcnl ccll~mcdiatcd eytoLOxicity O (O) Typc IJI hypcrscnsitivity

O (O) AdcnocarcinomD of the lung O (C) Leiolll}'osarcoma of rclrop:.'I'ilOnCUm O ~O) Cervical squalllQUS carcinoma

O (C) Localizcd <11laphylaxis O (O) Omnulomatous inOammation O (E) T-cell-mcdimcd cytOloxicily

O (E) Cerebral aslrocytoma

JO.

An inOamcd mucosa! suñacc makcs an ideal location fOl" lhe lransmission of HIV during sexual inlercourse. Which of lhe following cclls is inslrumental in lransmiuing HIV lO CD4+ T Iymphocytcs?

O (A) CD8+ cells O (O) O (C) O (O) O (E)

NK cclls Dcndritic ecUs Ncutrophils Plasma cclls

31. A 35-year-old hospitali7..cd fcmale has dcvclopcd an cXlcnsi\'c, scaJing rash during lhe pasl wcck.. A skin biopsy shows kcralinocytc apoptosis along thc dcrmal-epidcnnal jUoclion. wilh uppcr dcrmal Iymphocytic infilrrales. She also has jaundicc. Which of lhe following procedures has shc rcccntly undcrgonc?

O (A) Tubcrculin skin Icsling O (E) Chcmolhcrapy for malignanl Iymphoma

O

(C) Allogcncic bonc marrow lmnsplantalion

O (O) Penicillin thcrapy fOl" pncumooia O (E) Patch tesling for allcrgcn dctecliofl

33. A palicnl wilh mulliple myeloma dcvclops protcinuria, and yoo suspcct a diagnosis of amyloü:losis. Which of lhe following ICSlS or proccdurcs is lnos;l likcly lO cstablish lhe diagnosis of syslemic amyloidosis? X-r.lY film of lhe skull lo dclect bonc dcslruction Scrum leve! of caldum Scrum Icvcl of immwK>globulin ligllt chains Reclal biopsy staincd wilh Congo red O <E) Scrum Icvel of total immunoglobulins O (A) O (O) O (C) O (D)

For each of the c1ínical histories in questions 34 aOO 35, malch lhe masl c10scly associated lcucrcd sign, symplom. or physical finding: (A) (OJ (C) (D) (E) (F) (O) (1-1) (1) (1) (K) (L)

Arthrdlgia Bonyankylosis Endocarditis Lymphadcnopa!hy Myositis Pí.'I'icarditis PtIolO5CllSitivity Raynaud pllcnomcnon Sclcrodaclyly Sulx:lltancous nodulcs Urclhritis Xerophlhalmia

34. A 29-ycar-old felTh11e has difficulty c1imbing a singlc night of stairs. She has lillle diffieuhy in wriling or typing. Laboralory tí.'Sts reven! lhe presenee of 10-1 anlibodics and a scrum eremine kinase leve! 01' 45~ UlL. ( 35. A 52-year-old fClllalc is found 10 havc a chronic, dry cough and a pcrforuled Tlasal seplum. A mild inlerstilial nephrilis is presclll. as are amibodies lo SS-A and SS-B. ( ) 36. A 26-year-old female has had bouts of joim pain ovcr lhe pasl 2 years. She also has a skin rash on !hc chccks and bridge of lhe nosc. On physical cxaminatioo, she is foofld 10 havc no joint swclling oc dcformity, allhougll she has gcncralizcd IYOlphadenopalhy. 00 laboralOry tesling. shc is found lo ha\'c anemia. Icukopcnia. a pol)'c1onal gammopalhy, and prolcinuria. Hcr SCrulll antinuclcar anlibody tesl result is positivc al a Iiwr of 1: I024, with a rim paltcm idcntificd by immunoOuorcsccfICC. Whal advicc woold you gi\'c this palient?

O (AJ 01indncss is likcly to occur in thc ncxl 5 ycars. 32. A 20-year-old fcmalc prcscnls wilh acule renal faiJure o\'er thc past wcck. A renal biopsy shows immunoftuorescent staining positi\'c for 19 and complcmem C3 within lhe g101ncn.J1i. Thc clcetron microsoopic appearance of lhe biopsy is shown in lhe figurc. Oy which of lhe

O (O) Avoid cxposurc to cold cn\'ironments. O (C) Joim dcfonnilics wil! c\'cntually aceur. O (D) Chronic renal failure is likcly 10 occur. O (E) A cardiac va¡\,c rcplacemcnl will cvcnlual1y be requircd.


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Chapter 6

D1SEASES OF IMMUNIlV

41

37. In rL'tiponsc lo infcelion with MJctNHJcter;lUn mberCIIlosis, ;) granuloma fonns in lhe lung. Wilhin Ihe granulorna are cclls exprcssing c1ass 1I MHC antigens. 1bcsc cclls c1abor.lte cytokincs !hat promote fibroblaSlic production of collagen within the granuloma From which of lhe following pcriphcral blood lcukocytcs are Ihcse c1ass 11 antigenbearing cclls dcrivcd?

mislabcled. One of thcsc patients rcccives a blood lransfusion llUcr that day. Within an hour aftcr slartíng !he transfusion of red blood cells. the pmient bccomcs lachycardic aOO hypotensive aOO passes pink-oolored UJine. How is Ihis reactioo mcdiated?

O (A) Ncutrophil

O (8) Anlibody..iJcpcndent ccllular cyIOloxicity by NK

O (A) Rclcase of lurJlOl" necrosis factor-a inlo thc circulalion

O (B) Monocyte

O (C) B cell

cclls

O (C) Anligcn-anlibody complex dcposition in glomcruli

O (O) NK ccll

O (O) Complcmcnt-mcdiatcd Iysis of red bl00d cclls

O (El Basoph;1

O (E) Mast ccll dcgranulalion

40. A 45-year-old male prL'Si.'OLS wilh fc\·er. cough, and dyspnca worscning over lhe P.1S1 fcw days. A brollchoalvcolar lavage shows cYSLS of P. can·ni;. His C04 lymphocyte count is 1351pL. tolal SCI'UITl globuJiIl concentralion is 2.5 g/dL. and WBC eounl is 7800/,uL. with a diffcrcntial counl 01' 75 segmenle<! ncutrophils. 8 band ncutrophils. 6 IYlllphocylt..'S. 10 lTlonocylcs. and l eosinophil. Which 01' Ihe following positivc scrologic labormory findings would you most expccl?

O CA) Anlinetllrophil cytoplasmic 3utoontibody O (B) RheumalOid foclor O (O Antibodies to hum',m immunodcflciency O (O) Antistrcplolysin O O (E) Antinuclear 3n1ibody

viru.~

41. '1ñe boy in !he bubblc" was a famous expcrimcnt in lhe trcalme", 01' a primary immuoodcficiency disorder by isolafing lhe palicnI from polcntial pathogens. This boy slancd life with a hypoplastic lhymus. He hoo small Iymph nodcs Ihat lacked germinal ceoten;. aOO gut-associatcd Iymphoid tissuc was seant. His lotal Iymphocyte count was \'ery low. and his total scrum g10buJin eoncentration was diminishcd. How is this disorder now trc.1Icd?

O (A) Chemotherapy O (B) Allogcncíc bone rnarrow transplantation O (C) Conicosteroid mcrapy O (O) llltravenous illlmunoglobuJin lhcmpy O (E) Alllibiotic Iherapy ÚlUf1e;y or Dr. Richard Soothcimcr. Department or Denlllllology. Unil"er. or Te~as Soulhwestem Medica! School, I)¡tll¡r;., TX.

$ily

38. A l7-year-old fcmale has sc\'(,Tal dise-shapcd. slightly raiscd. crylt\cmalOUS Icsions localcd o\'cr her lnmk aOO thighs. Thc lighl microscopic aOO immunofiuoresccm (Wilh anlibody lO IgG) a~amnces of a sldn biopsy are shown hcrc. Which of the following conditions docs lhe palienl most likcly ha\'c1

O (A) Limitcd sclerodenna O (B) Sj6grcn syndrome O (C) SLE O (O) Rhcumaloid arthritis O (E) Dcrmatoll1yositis

39. l..<lboratory tcsts are ordcred for I\VO paticnts on II hospital ward. Howcvcr. during Ihe phleholomy proccdurc. lhe Vaculainer lubes dmwll from ¡hesc two paticnts are

42. A 9-ycar-old girl had pain and swelling 01' her efbows and knccs for a month, wlth rever to 3SOC.•·Ier ¡x:ripheral WBC coonl was e1evated. Shc had a posilÍve anlinuclcar antibody lesl rcsuh bul negative rcsults for rhcumatoid fa¡;;.. lor. Sd-70. aOO SS-A serologit..'S. Several yeano laler. hcr symptoms abaled. never lo rccur again. She most lib:ly had O (A) Systemíc sclerosis

O (B) Juvcnile rhcumatoid anhritis O le) Psoriatic anhropathy

O (O) Ankylosing spondylilis

O (E) Rcilcr syndrome 43. A 9-month-old child prcscnls with a history of recurrent infCClions wilh multiplc agcnts. induding eYIOHlcgalovirus. Candido (a fungus). and staphylococci. A carcful f<llllily history and IX:digrcc allalysis rcveals this to be a gellt.'tic disordcr mal is inhcritcd in an autosomal rcccssive


42

Pon 1

GENERAl PATHQ.OGY

panero. Of lhe labor.llory tests lislcd (all of which are relC\'anl), which Orle is likc1y to be lhe mosl IIsefill in CSlablishing lhe undcdying mcchanism of iuullunodcficiency?

O (A) O (B) O (C) O (O)

Quanlilalive scrurn immunoglobulin 1C\'cls Enumeralion of B cclls in lhc b100d Enumeration of CD3+ cclls in blood Tests of nculrophil funelion O (E) Adenosinc deaminasc lADA} Icvcls in leukocylcs 44. An acUlC pharyngilis is diagnoscd in ¡¡ 12-ycar-old girl, and lhroal culturc grows group A (3-hclllolylic slrcplococcus. The pharyngitis rcsoh'cs. bul 3 wccks laler. shc dc"c1ops ches! pajn wilh fever. I-Ier anlislrcplo1ysin O (ASO) liter is 1:512. By which of lhe following immunologic mechanisms has Ihe cardilis de"cJopcd?

O (A) Breakdown of T-ccJl ancrgy O (B) Polyclonal /ymphocyte aclivation O (C) Rclea.se uf scqUCSIcn:d antigens O (O) Molecular rnimicry O (E) Failurc of T-cell-mcdialcd supprcssion

45. A 32-year-old ITh11e has experiellccd nausea and vomiting for lhe past wcck and is mi Id/y icteric. His lierum m;paJ1ale amillolnmsfcrasc Ievel is 208 U/l :md u/anine mnillolrall.<;fcmsc lcvcl ili 274 VIL. A liver biopsy shows focal demh of hcpalocylcS wilh a portal inliltmle composcd mainly uf Iymphocyh:s. Scrologic fiOOjngs indicate positivily for hepatitis B surfacc antigen (HBsAg) alld hepalilis B corc antibody (HBcAb). '11lc masl Iikcly rncchanism by which thc li\'er cell injury occurs undcr Ihcsc condilions is

O (A) Recognilion of 1-lBsAg by lhe C08 molecule of T ce/U; 0(8) Ra;ognition of an anrigenic pcpIide prescnled by MHC class I moleculcs lO NK cells O (e) Recognition of an amigenic pt.-ptide prcscnted by MHC cJass I molccule to C08+ cclls O (O) Dcstruction of HBli anligen-cxprcssinll cells by anliHBs IgG amibody (E) Apoplosis of the liver cdls by cytokines l"c1ea~cd by activatcd lTIacrophagL"S

o

47. A 28~year-old malc presenls wilh a 2-day hislory of Iu..'moptysis aoo blood in urinc (i.c.. hernaluna). He dcvel· op!> acule renal failufC. Renal biopsy shows g10rncrular damage and linear immunofluoresccnce wilh labelcd anlicomplcmcllI antibody. ( )

For cach of the c1inical histocics in qucstions 48 aOO 49, match Ihe mosl c10scly associaloo lellcn.xi cell Ihal partiei· p.1tes in 3n immunologic response. (A) C[)4+ lymphocyle (B) CD8+ /ymphocytc (e) Eosillophil (D) Epithclioid cell (E) (F) (G) (H) (1) (J) (K)

(l) (M)

(N) (O)

Fibrobla~t

Follicular dendritic cell Macrophage Mase. cclJ

Neulrophil NK ccll Plasma cell Pre-B ccll Pro-T cell Stcm ce" Typc 1 hclpcr T cdls (Tul)

48. A 40-year-old male is knowll lo have bren infeclcd with HIV fOl" the pasl 10 years. He has oc'Cn bothercd in lhe pa<;1 wilh oral caOOidiasis bUl has had no major illncsscs. He is diagnoscd wilh Kaposi sarcoma invo1ving the skin. He has cxpcdenccd a 2O-kg weigln loss in lhe pasl 6 Illonths. His HIV-I RNA viral load is 60.000 copicslmL. Which typc of cell is dcplclOO Ihe masl in his Iymph nades? ( l -19. As a 4--ycar·old child. this paticm had recurrenl sino· pulmonary inft:clions wilh StaphyloCtx:cus allrellS aOO Slrel)tOC()(;Cfl.~ pnellfflolliae; he also devcloped an anhritis tba! dearcd wilh illllllunoglobulin lherapy. The gcnninal centen; of his lymph nooes are rudimenlary, and he has dcvclopcd SlE. Which typc uf ccl/ failed lo diffcrenliale? ( )

For caeh of lhe c1inical sccnarios in qucslions 46 aOO 47, sc1ecl tbe mosl likely antibody lhat will be positive:

(A) (B) (C) (O) (E) (F) (G) (H) (1) (1)

Ami-double·Slr.mdcd DNA antibodies Antibody 10 Sm antigen Anti-histonc anlibody Anli-Jo-l anlibody Anti-UI-riboncuclcoprolcin anlibody Allli-ccnlromere antibody Anli-SSA anlibody Anli-ba.<;Clflcnl Illcmbrane anlibody Anli-phospholipjd ,11llibody Anlibodics ngninsl desfIlosnllles

46. A 60-year-old fcmale is bcing trcalcd wilh hydrdla:tinc for long-standing hypcrtension when she devclops somc clinica1 fealures liuggestive of lupus L'rylhcmatosus. Initial 1aboratOfy tindings inelude anlinuclcar :mlibody lilCfS of 1:2560 in a diffusc paltem. Anu-double-slmndcd ONA anlibodies are not prcscnl. ( )

50. A 61~ycar-old ma1e prcscnls wilh decrcasing renal funclion marl:cd by rising. conccntmlions of .serum ercatininc and urca nilrogen. A renal biopsy rc\"cals lhe micro-


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scopic appcarance shown in lhe figure aOO urinalysis de11lonslralcs Bence Jones proleinuria. Which of lhe following undcrlying condilions is he fnosl likely to ha"e?

O (A) Rhcumatic fever O (8) O (e) O (O) O (E)

Multiple mye!oma Ankylosing spondylilis Syslemic sclerosis Common variable immuoodeficicncy

DlSEASES OF IMMUNlTY

43

thc past 10 ycars, although she has ha<! rcmissioos with cach of hcr lhree prcgnaucics. Shc has becn bedriddcn for lhe pasl 2 monlhs. A joinl aspiralc shows tUlbid fluid wilh many neulrophils conl3ining phagocytizctl immune cornplexes. She has no m)'ositis or rnsh. A painless subcutaoo0t1S nodule is prcscnl bchind lhe clbow joinl o\'er lhe olocTaoon proccss. Which of lhe fol1owing long-Ienn outcomes of her dist:asc is fllOSl likdy?

O (A) O (B) O (C) O (O) O (E)

Chronic renal failure Aortic dissL'C{ion Vcrlebr,11 kyphosis Adcnoc.mcinoma of the colon Jmnt dcfonnitics

54. A 48-year-old rema le has kcratoconjunclivitis. Shc also has oral mucosal auoptJy wilh bucca! mucosal ulccrmion. A biopsy of hcr lip re\'cals markcd Iymphocytic aOO plasma ceH infillrales in minor salivary glands. Which of thc following antibodies is most likcly lo be foond for this palienl?

O (A) Anti-double-stmOOed ONA O (8) Ami-ecntromere antibody O (e) SS-B O (D) Sd-70 COlines)' of Dr. Lollis Picker. Oepanmenl ()f P:llholoIlY. Uni\'cl1\ily of Texas SOllthwcslem Medical School, Dalla.~, TX.

51. Thc skin of a 40-year-old male labaralO{)' tcchnician is shown hcre wilh immullOSlaining using antibody lo CD4. A IQ-mm-diamcler arca of red. induratcd skin has pcrsistcd for the pasl 2 days after accidental injcctioo of a chemical. Which of the following imnmnologic rcaetions is mosl consiSlenl with Ihis appearance?

O (A) Systemic anaphylaxis O O O O

(8) (e) (O) (E)

Arthus rcaction Grafl-\'crsus-host discasc Dclaycd-typc hypcrsensilivily Scrum sickness

52. A 19-ycar-old fema/e wilh chronic renal failure received a cMaveric rcn:11 transplant. A month Ia.ter. she cxpcricnct:d a.cule renal failurc, and a renal biopsy was perfonllcd. Shc was thcn lreated wilh conicostcroids. aOO hcr renal function impmved. Which of lhe foUowing changc.s was most Iikcly scen in thc biopsy bcfore cortieostcroid lhcrapy?

O (A) Illtcrstilial infiltTalion by C03+ Iymphocytes and tubular epithclial damage

O (B) Exlensivc fibrosis of thc interslilium aOO glomeruli Wilh marl::edly thickcl'lCd blo<Xl vesscls O (e) Fibrinoid necrosis of renal arterioles with thrombotic occlusion O (O) Inlerslilial infi1tmtion by eosinophils wilh tubular epilhclial dmnagc O (E) Deposilion of pink hyalinc lll.1tcrial in Ihc glomcruli, which stains red with Congo n . d aOO shows grccn birefringenec under polarizcd light 53. A 35-year-old female has had 1>0015 of sc\'ere pain and swclling of the sn1<111 joints of bolh haOOs aOO frel fOl'

O (E) jcrl

55. Within minmcs afler an injcction of pcnicillin G, a 22-year-old male devclops ilChing aOO L't)'thcma of his skin. This is quickly followed by scvcre rcspiralüfy difficulty with whet:zing and SlTÍOO"'. Which of lhe following immuooglobulins has bttOIllC attachcd to the penicillin G aOO mast cclls lO produce these symplorns? O (A) IgA 0(8) IgG O (e) IgM

O(D) IgD O (E) ¡gE 56. A 4-year-old boy has had rocllrrclll rcspirmory inf(X;(ions wilh multiple b.1cterial and viral pa.lhogens. He also has eczema involving tmnli: and extrcmitics. Laboratory findings inc!udc a plalclel eounl of 71,OOO/j.A.L. IgG Icvcl of 1422 mg/dL. IgM concentration of II mg/dL. aOO IgA Icve! of 672 mg/dL Thc WBC eOllnl is 38OO1JLl.. wilh a differcnlial counl of 88 segmented nculrophils. 6 bands, 3 Iymphocy~, aOO 3 monocytes. This p.aliem is at an incrcascd risk of de\'cloping

O (A) Hypocalccmia O O O O

(B) (C) (O) (E)

Rhcumaloid anhritis Glomeruloncphritis Malignam Iymphoma Demenlia

57. A i7-year-o/d boy is found 10 have a positive serologic l(,"St rcsult for HIV. He is curremly well. He is not an injcclion drug uscr, but he has bccn scxually active for 3 ycars. What is thc besl ad\'icc fOl' lhis palienl?

O (A) You should p<nons.

not have unprotcctcd scx with

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44

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Par! 1

GENERAL PATHOLOGY

o

(B) You will prooobly devclop AIOS wilhin Ihe ncxt year. O (e) Your I-IIV lesl may bccome negalive wilhin Ihe nexl yea... O (O) As long as you are c1inically wel!. you can donale blood. O (E) The coursc of your infeclion is besl followed by liters of anli-HIV anribodies.

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l. (A) She has fealmes of SLE. Pmients with SLE onen have a skin rash on ~lIn-exposcJ i\rea~. A llfClhrilis is more characterislic n( Rcitcr syndmmc. one 01" lhe spondyloar+ Ihropathics. Difficully in swallowing is a fcalure of sclercrderma. XerOslomi¡¡ suggcsls Sjogren syndmme. Though SLE ha~ gcnetic associations wilh complemcnl deficicncics or I-ILA-DQ. malfomlalions are 1101 a fealurc of SLE. Congcnilal hean disease may be secn wilh DiGeorge syndrollle.

BP6 103

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PBD6 217

2. (B) This palienl has c1inical anJ l;erologic fealures of SLE. Shc also has a falsc-posilivc lesl rcsult fOl" syphilis. indicming Ihe prcsencc of anlicardiolipin anlibodics. These antibodics against phospholipid-prolcin cornplexes are also called lupus anlieoagulanls bccause Ihey interfere wilh in vilro c1utling lesls. Howevcr. in vivo. Ihey are thmmbogenie. Hence. Ihese p.'lienls can have recurrent Ihrombosis. Lupus anlictl<1gulanls can also oceur in lhe absencc of lupus in SUllle patienls.

BP6 103 PBD6218 3.

(8) Entry of HIV inlo cdls rcquircs binding lo Ihe

C04 1110lecule :md co-rt:ceptor molccll1cs such ¡¡S CCR5 58. A 79-year-old m¡¡le has expcrienced wOrJ;Cning congeSlive hcart failure wilh pulmonary edema and peripheral edema. Echocardiography rc"eals cardiomegaly wilh fourehambcr dilalion. AII laboralory leslS. including scrum protein c1cctrophorcsis and cxaminalion of bone malTOw slllear. are nonnal. An cndomyocardial biopsy shows Ihe hislologic appcarance represcntcd in Ihe figure. Which of thc foilowing proleins is most likcly to be found in this lcsion?

and CXCR4. lllCSC HIV co-rcceplors are rcceplors for chemokincs on Ihe surfacc of T cel/s and macrophages. Mutalions in genes cncoding Ihesc co-rcceplor molccllles makc individuals rcsislaJJl lo Ihe cffecls of HIV infeclion bccause I-IIV ~nnOl enler lymphocYIL"S and macrophages. The olher cell sllrface rcecplors are nol rcle"allt for I-IIV enlry into cells.

O O O O

4. (E) She has fcaturcs of SLE. The i.lIllinuclear anlibody lesl resull is nearly always positivc for persons wilh SLE. Thc presence of anti-double--strdllded DNA or anli-Smith anlibodies is more spceific for SLE lhan for olher auloirnmune discascs. An c1evalcd ASO liler indicalcs a previous group A slrcplococcal infcclion. HLA-B27 is slrongly a<;sociated wilh spondyloarthropathies. sllch ilS 3nkylosing spondylilis. Masl pcrsons wilh SLE have a polyclonal gamlllopathy wilh incrcascd serum IgG. RheUlll¡¡loid factor is scen wilh rheulllatoid al1hrilis. which is unlikely to be accompanicd by a malar msh and, more importanlly. is associatcd wilh joinl dcslruclion and fibrosis.

(A) Alpha-fcloprotcin (B) Bel<l:!-microglobulin (e) Translhyrctin (1)) Calcilonin O (E) 'gE

59. A 2-year-old bay hao; had allnosl cuminuous infec(ions since 6 Illonths of age. These infeclions have inc1uded otitis media. pneulllonia, and impeligo. Organisms cullurcd have included Haelllophi/us injlllellwe. S. plle/lll/Oniae. and S. al/reus. He has also had diarrhea. with Gillrl/ia /wnblia cysls idcmified in slool specimenl;. Family hislory re"eals tha! an ulder brolhcr who prCl;enlcd wilh a l;illlilar condition died bccausc of overwhclllling infcclions. His IwO sisters and oolh parents are normal. Which of Ihe following laboralol)' findingl; is mosl likdy for Ihis boy?

O O O O O

(A) (B) (e) (O) (E)

Absent IgA Dccrcased co1l1plemem O I-ligh liler of HIV-I RNA Markedly dcereased illlmunoglobulins Posilive antinuclear anlibody tesl

BP6 119-120 PBDó 242

BP6102-104

PBD6216-218

5. (n) Shc has expcrienccd a syslcmic anaphylactic rcaction fmm a Iypc I hypcrsensilivilY reaclion. Epinephrinc is Ihe faslCsl acting agent lo lreal Ihis life-lhrcalcning condition. Cyclosporine is uscd to minirnize Iransplanl rcjedion. Penidllin is an amibiotic th<JI often induces a typc I hypcrscnsilivily rcaclion. GluceX':0I1icoids can reduce imrnune rci.Ictions. allhough over days lo wccks. Mclholrexmc is uscfui lo lreal gmlí-versus-host disease.

BP687-89

PBD6197-199


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6. (E) Shc has SLE. These paticnts C;ln dcvclop ano-red cell antibodies that can cause a hcmolytic anemia. Cytopenias. including leukopenia., lhrombocytopcnia. an<! anemia, are common with SLE.

BP6 103 PBD6 211 7. (1) She has psoriatic arthropathy. The arthritis in this condition can c1inically and pathologically resemble rheurnatoid arthritis. Like other spondyloonhropmhies, sacroiliitis occurs in patients with psoriatic anhropalhy.

BP6 112 PBD6 1252 8. (B) He has a sclccti"e IgA dcficicney. Such pcrsons are bothered by minor recurrent sinopulmonary infeclions aOO by diarrhca. Pllellmocystis infCClions are scen in patients wilh more !>Cvere acquired or inhcrited immunodeficieney disorders affecting cell-mooiated immunity, particularly AIOS. Hepatitis infedion." are not directly rclated to immunodeficiency slalL"S, although AJOS p.1ticnts with a history of injection drug use are often infeetcd with hepatitis B or C. Rcsistance againlit fungal and viral infcetion is medialed by T cells.

BP6 116 PBD6 234 9. (D) He h..lS AIDS with Kaposi sarcoma of the skin. Kaposi sarcoma is associaloo with a hcrpcsvirus agent thal is sexually lransmiucd: human herpesvirus 8 (HHV-8). also caUed the Kaposi sarcoma herpcs\'irus. Other herpesviruscs are not imroh'Cd in the palhogenesis of Kaposi sarcoma, althoogh t.hey can be frcqucnl with AIDS. HlV. although present in tlle Iymphocyt.es and monocytes. is not dclectcd in the spiOOle cells lhat prolif<:ratc in Kaposi sarcoma. Ot.her lhan thc \'llrÍccUa zosler virus. which is associatcd with thc appcar31lCC of dermatomally distrihttted skin \-t'$iclcs known as shingles, skin lesiOllS are not COllllllon for cytomeg. alo"irus. Epstein-Barr "irus, oc adenovirus infcctiOllS. BP6 125 PBD6 248 10. (A) CD4 cclls of the TIl2 typc are csscnlial to the induction of Iype 1 hypcrscnsitivity bcCllUSC lhey can se· crete cytokines slIch as inlcrlcukin (TL)-4, IL-5, IL-3. and granulocyle-ll1acrophage colony-slimuli'lting faclor. which are n:quired for Ihe growlh, recruitmcm, and activalion of mast cells and cosinophils. NK cells can Iyse other cells. such as vims-infcctcd cclls, withoot prior sensitization. Macrophages can secrete a varicty of eytokines. bul they are not essenlial lo typc r hypersensilivity. Dcndrilic cells lrap amigen aOO aid in antigen prcsclllalion. Ncutrc>plils are rccruitcd by cytokines lo participate in acUle inflammalOf)' reactions.

BP6 B1

PIlD6 196

I J. (E) Shc has dennalomyositis. a form of inflammatory myopathy in which eapillaries are lhe primary target foc anlibody wK1 complcmenl-mcdialcd injury. Ami-Jo--I anlitxxI.ies. although not presenl in most cases. are quite spe· cific foc inflammatory myopalhies. 1be pcrivascuIar and pcrirnysial inflammalory infihrates resull in peripheral musele fascicular myoc)'te necrosis. The prQCt.'Ss is medialed by CD4+ rells and B cclls. Thc hcliotropc rash is a characleristic feature of dennalomyositis. Anti-double-slranded DNA is sp<.'cific for SLE, in which Ihere can be a rnyositis

DlSEASES OF IMMUNITY

45

withoul significant inflammation or necrosis. RhcumalOid arthritis is accompanied by inflammatory dcslruction of joints, not Illuscle, although Illuscle may atroplly sccondary to diminishcd mo"emenL Thc anti-UI-ribonuclcoprotein antibodics suggesl a diagnosis o( mixed cooncctive lissu~ disease. a condilion l!lal can overtap Wilh polymyositis. Anti-ruslone antibodies are associaled with drug-induccd SLE.

BP6114-115 PBD6 230-232 12. (B) Thcse are thc "wire loop" glomerular capillary Icsions of lupus ncphrilis. Ami-Sm aOO anti-dooblestranded ONA are specilic for SLE. However, ami-Sm is prcsent in only 25% of cases. ScI-70 is a marker for diffuse systemic sclcrosis. 10-1 is masl specific fOf' polymyo-silis. HLA-B27 is sren wilh ankylosing spoOOylitis. Anticentromcre antibody is seen most often with limited scleroocrma.

BP6 104, IOB PBD6 21B, 222 13. (A) This is an example of anlibody-dcpcndenl ccl1medimed cytotoxicity direclcd at a pamsitic infection. IgG and IgE antibod.ies bcaring Fc rcceptors coat the parasite. Macrophages. NK cells, and neutrophils can rccognize the Fc receptor aOO Iysc the antibody-eoaled targel cclls. Complemcnt-mediated Iysis is mosl typic:al for immune dcstruction of red blood ccl1s with hcmolysis. Langhans giant cclls are seen in granulom.3lotls inflammation. a fonn of type IV hypersensitivily. Acule inflammalory rcactions have liule effect against tissue parasites. Lcukotriene C. is a potent agenl that promotes "ascular permcability and hronchial smooth muscle conlraetion in type I hypcrscnsitivity rcaetions.

BP69O-91

PBD6 200-201

14. (B) This is chronic rcjcction. The progres.<;ive renal failure results from ischemic changes with vascular narrow· ing. Celf lysis with macrophages i~ typical for anljbodydcpcndent cell-medialed cytoloxicity Ihm does not playa key role in chronic rejcclion. Gmnulomatous inflammation ís nol typical for Iransplanl rejection. Release of lellkotriene C. from masl cells is a fcature of typc I hyperscnsitiv¡ty. Complement-mcdiated ccll lysis can occur whcn antidonor anlibodics are prcfomled in Ihe hosl, as occurs in hypemcute rejection.

BP69B

PBD6 210

15. (A) NK rel1s have the ability to respond without prior sensilization. They carry rcceptors for MHC c1ass I moleculcs thal inhibil lhcir l)'tic function. Whcn exprcssion of dass 1 MHC molecules is roouccd on the ccll surfacc. thc inhibitory rcecptors on NK ce1ls do not rcceive a negalive signa!. 1be <:ell is killcd. NK cells are oftcn !he fi~ linc of <k.'fense against viral infcetion. Neutrophils prm'Ídc a nonspecific immullC response. primarily to bacterial inf<:clions and not lO intriICCllular viral infcetiOn<>. Macrophages can process amigen aOO can phagocytizc nocrotic cclls. CD4 cclls are helpcr T rells thal assiSl othcr rells. such as NK reUs. macrophages, and B re1ls, in lhe ¡mmune response. Oendrilic ccl1s help in antigen presentation.

BP6 B3

PBD6 191


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GENERAL PATHOLOGY

16. (E) Therc is a failure of Icnninal diffcrcnliation of B cclls inlo IgA-scercting plasma cclls. Lack of IgA in mucosal sccrclions Icads to incrcased risk for rcspiratory and ga<;trointcslinal infcetions. Therc are IgA anlibodics in scrum that can Icad to a Imnsfusion rcaclion wilh IgA in donor SCnlm. Persons wilh scvcn: combincd immunodcficiency (SCID) do nol livc this long with such mild infce~ lions. HIV infcetion is markcd by failurc of ccll-mcdialcd immunity. The DiGcorge syndromc manifcsls in infancy with failure of cell-mcdialcd immunity from lack of funcIional T cells. Wiskolt-Aldrich syndromc is associatcd wilh cczema and Ihrombocytopcnia. BP6 116 PBDó 234 17. (C) This hislory is Iypical of the lale-phase reaclion in Iypc I hypcrscnsilivity. Thc inilial rapid n:sponsc is largcly causcd by degrallulalion of masl cclls. Thc lalc~ phasc rcaclion follows withoul addilional exposurc lO antigcn and is characterizcd by more intense infiltralion by inflammatory cclls such as nCUlrophils, cosinophils, ba<;ophils. monocyles, and CD4+ Iymphocytcs. Thcre is more tissue dcstruetion in this lale phase. BP6 BB-B9 PBD 196-19B 18. (B) Maerophagcs can bccomc infcetcd with HIV and are not dcstroycd likc CD4 cells. Instead, macrophages survivc to carry thc infcetion to tissucs throughoul the body, particularly the brain. HlV infeelion of lhe brain can result in cnccphalitis and dcmclllia. NK cclls and nculrophils play no significanl rolc in HIV infeclion. C08 Iymphocytes cannol be infeclcd wilh HIV. Langcrhans cclls in mucosal surfaces may aid in initial HIV infcetion of C04 Iymphocylcs. BP6120-121 PBD6241-243 19. (e) This is a localizcd immune.-complcx rcaction (i.c., Arthus reaclion), which activatcs and deplctcs complc~ mcnt C3 and C4. IgE conccntralion is incrcmicd in pcrsons wilh alopy and the potenlial for Iypc I hypcrscnsilivity. Although nculrophils are being rccruited locally to thc inftammalory rcaclion in Ibis casco Ihey are nol deplclcd systemically, and they may be incrca<;cd in the circulalion. Skin tesis are measurcs of Iypc IV hypcrscnsitivily whcn antigens such as tubcrculin are uscd. CD4 Iymphocytes a<;siSI in a variety of antibody alld ccll-mcdiatcd immulle reaclions, bul their numbcrs in p<-Tiphcral blood do nol change apprcciably. BP6 93-94 PBD6204 20. (C) In chronic inRarnmatory conditions such as mcumatoid arthritis, Ihc SAA precursor protein forms the major amyloid fibril protein AA. Amyloid is dcposilcd in illlcrstitial localions. not intmccllularly. The P component is a minor component of thc amyloid. AIl amyloid demonSlrates the characterislic "applc grcen" birefringencc undcr polari7-OO ligbt microscopy after Congo red staining-anything cisc would nol be amyloid. Amyloid derived from light chains in associalion with multiple mycloma has AL fibrils. BP6126-128 PBD6251-253

21. (G) Mixed connective tissue discasc has fcatures of SLE. polymyosilis, and Sj6gren syndromc. Unlikc SLE. scrious renal diseasc is unlikcly. BP6 115 PBDó 231 22. (C) This patient has cutancous and visccral manifcstalions of diffusc systemic selcrosis (i.c.• diffusc sclcrodcrma). Raynaud phcnomcllon, skin changes. and csophagcal dysmotility can also occur in limitcd selerodcrma (i.e.. CREST syndrome). but lung involvcmenl docs noto BP6114 PBD6227-228 23. (C) This patient has scvcrc combincd immunodcficicncy (500). Becausc thc T· and B-cell arllls of thc immune sYSlclll are dcficicnl. thcrc are scvere and recurrenl infections wilh bactcria. viruscs. and fungi. With the family history of malcs being affceted, Ihe patien! most likcly has X-linkcd SOl). This fonn rcsults from mutations in Ihe common 'Y chain Ihat is a part of many cylokinc reccptors such as IL-2. IL-4, IL-7. and 1L-15. Thcsc cytokincs are nceded for normal B- and T-cell dcvclopmcnt. Loss of chromosolllc 22q 11 is secn in l)iGcorge syndromc. brk gcnc mutations give rise to Bruton agammaglobulincmia. Mutation in CD4ü ligand is responsiblc for hypcr IgM syndrome. BP6117 PBD6234-236 24. (C) She has fcaturcs of myaslhcnia gmvis, a fonn of type 11 hypcrscnsitivity rcaction in which anlibody is directcd against cell surfacc rcccplors. Amibodies to aeetylcholine rcceptors impair Ihc funclion of skcletal muselc mOlor cnd plates. Anlibodics are produccd by B ccUs. and macrophagcs are not a signilicam part of Ibis hypcrsensiliv. ity reaction; Ihcn: is little or no inftammation of the musclc wilh myaslhcnia gmvis. Musclc Iysis by CD8+ T cclls occurs in polymyositis. Immunc complcx-mediated injury is a fcalure of dcrmatomyositis. Dclaycd hypcrscnsitivity reactions are morc likely in parasitic infcstations of museles. BP6 90 PBDó 201 25. (E) Shc ha.; difTuse systcmie sdcrosis (i.c.• sclcrodcnna). The small artcrics of Ihe kidncy are involvcd with a hypcrplaslic arteriolosclcrosis. which can be complicaled by very high blood prcssurc and renal failurc. Mcningitis and adrcnal failurc are not typical features of autoimmunc disea'óes. Wilh sclerodcrma, the gaslrointestinal traet undergocs fibrosis, wilhout any tendcllcy lo pctforatioll or ulcer· ation. Gloll1crulonephritis is a more typical complication for SLE. BP6 112-114 PBD6226-229 26. (A) This is DiGcorgc syndromc. The Ihymus, parathyroids, aorta. and hcart can be involved. T-cel\ function is dcficient, rcsulting in recurrenl and multiplc fungal. viml. and prolOzoal infections. Failurc of B-ccll maturalion lo plasma cclls is onc Illodc of dcvclopmcnt of common variablc ill1munodcficiency. SOIl1C cases of 501) are causcd by lack of ADA. H1V infection does nol cxplain tbc hypocalecmia al birth. Failure of pre-B cell maluration rcsults in Bruton agammaglobulincmia. BP6 116-117 PBD6235


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DlSEASES OF IMMUNITV

47

27. (A) Allbough nol provcd, thc C04 Iymphocytes are thought to respond to some unknown anligenic stimulation, releasing eytokines thal furthcr activate macrophagcs and mast cells. The result is cxtcnsivc dcrmal fibrCl'>is lhal produces the c1inical appcarancc of sclerodaclyly with sclerodcrma. Neulrophils and NK cells do not participale in this process. [)espile sclerodenna being an auloimmune diseasc, inflammalion is mínima!. The major finding is progrcssive fibrosis of skin, lung, and ga"itrointcstinal tracto

rcsult in acUlC inflarnmation. Anlibody-depcndcnl cell-mediated cytotoxicity is initiated by IgG or IgE coating a target to attract cel1s that arreet l)'Sis, aOO immune complexcs do not form. Localizcd anapnylaxis is a Iypc I h~rsensilivity medialcd by IgE antibody. GranulomalOllS inflammalion aOO T-eell cytotoxicity are fcatures of type IV hypcrscnsilivity.

BP6 113-114 PBD622B-229

33. (D) Thc diagnosis of amyloidosis is bascd on lighl microscopic demonstratioo of amyloid in tissues with Congo red staining. Multiple m)'c1oma can produce Iytic skuU lesions, although not in all cases, aOO such Icsions are not always accompanicd by amyloidosis. Hyracalccmia occurs fTcquently with m)'c1oma because of thc Iytic skdctal Icsions, bul il does not predicl amyloid dcpositioo. lbc cOllcenlralion of light chains in scrum 01' urine can be clevated without amyloidosis, as can Ihe lolal serum ¡mmunoglobulin.

28. (E) Her original symp(oms, although nonspccific. are secn in more than one half of aduhs with acute HIV infection. 1bc average time lO development of AIOS is 8 lo 10 years, wilh the onsct of opportunistic infectioos as the C04 cell counl falls below 2001p.L. SpondyloarthropaIhies aOO auloimmunc disca~ such as SLE or sclerodcnna are nol likely lO have such a long inlerval belwcen illnesses and are nol as likdy lO have opportunislic infeclions wilhoul irnmunosuppressive therapy. Pt:rsons with AIDS may have a polyclonal gammopalhy bul nOI marked hypogarnmaglobulincmia.

BP6 122-124 PBD6 245-246 29. (A) Opportunistic infections in un intra\'cnous drug abuser suggcsl a diagnosis of AIDS. 1bc mCl'>1 common ncoplasms seen in association with AJOS are B-<:cll nonHodgkin Iymphoma uoo Kaposi sarcoma. A rafe tumor a~<;()Ciated wilh AIDS in childrcn is leiomyosarcoma. Cervical dysplasias llnd careinomas are incocased in womcn with HIV infeetion. but such lesions are Icss frequent than Iymphoma. Lung cancers al her age are nol comrnon in any cUcumstancc. Opportunistic infcetions of the brain are common in AIDS, as are central nervous system Iymphoma~ bul nof g1iaJ ncoplasms.

BP6 124-126 PBD6247-250

BP692-93

PBD6201-203

BP6 126-128

PBD6251-253

34. (E) She has polymyositis. Muscle wcakness in polymyositis lcnds lO be symrnctric and proximal. This condition differs from dennalom)'OSitis in that there is no skin invol\'cment, and typically polymyositis affcclS adulK Her skclctal muscle on biopsy shows infiltralion by Iym~~ cytes along wilh degencration aOO rcgencnllion of muscle fibcrs. Thc lymphocytes are cyloloxic CD8+ cells.

BP6115 PBD6229-231 35. (L) She has Sjogrcn syndromc. This is characterized by immunologically mcdiated dcstruction o( salivary and lacrimal glands, as wdl as othcr exocrine glands, Iining the m;pirnlClry aOO gastroinlestinal Iracts. Dryncss an<! crusling of thc nose can lcad 10 pcrforntion of nasal seprum. In 25% of cases, cXlraglandular tissues such as lung, skin. kidncy, and muscles may be ¡nvolved.

30. (C) Thrce Iypcs of cclls can cany HIV: dcndritic cells, monocytcs, and CD4+ T cclls. Mucosal dendrilic celL~ (Le., Langerhans cells) can bind to lhe virus and lnmsport it lo C04+ cells in the Iymph nocles. Whether the virus is intemalizcd by mucosal dcndrilic cells is not clcar. Monocytcs aOO CD4+ T cclls expres... C04 and the co-rcccp(ors (CCR5 aOO CXCR4), aOO thereforc HIV can entcr these eells. FoUicular dcOOritic cells are dislinct from mucosal ()r" cpithelial dendritic cells; they lrap antibody. coatcd HIV virions by means of their Fe rcccplors. lbc othcr listcd cclls cannot be infected by HIV.

36. (O) She has SLE. Many pcrsons with SLE have glomerulonephritis ¡md evcnlually devclop renal failure. Blindncss is uncommOTl wilh SLE. Raynaud phenomenon can be secn wilh many llutoimmune discases but is most troublcsome with sclcrodenna. Allhough synovial infiammation is common with SLE. joint dcformity is rare. The übmanSacks endocarditis of SLE tends lO be nonderorming and limilcd. II is uncommon these days bccause of the use of COrtieOSleroid Ihcrapy.

BP683 PBD6 191

BP6 106-108 PBD6 220-222

31. (e) This ¡s grl.lft-ver:sus.hoSI disca~. The engrnfted marrow conlains immunocompctent cclls thlll can prolifcr+ ate llnd auack host lissucs, usua\ly skin, liver. and gastrointestinal epithelium. Tuberculosis skin tcsting is a fonn of delayed-typc hypersensilivity. Some ehemotherapy agents can produce a drug rcaction with more acute inflamrnatiOfl. Urticaria with Iypc 1 hyperscnsitivity is a typical reaction to penicillin thcrnpy. Patch testing is done to detcrmine thc typc of allergcns 10 which atopic persons may reacl.

37. (B) Bload monocytcs express MHC cJass 11 antigens and can migralc into tissucs lo beeoHIC macrophagcs. In tuberculosis. these macrophages lransform iTllo epithclioid cells, thus fonning a granuloma. Macrophages play an important rolc in dclayed hypcrscnsitivity rcaclions with ccll+ mediated immunity. Ncutrophils are importanl mainly in acute inflammatory responses, although thcre may be somc of thcm in a grunulomatous reaction. B eells fonn plasma cclls thal secrete immunoglobulin on slimulation aOO are csscntiaJ lo humoral immunity. NK cclls can fundion withOUI prior sensitizatiQn. Basophils may playa role in JgEmcdiatcd responses.

BP6 99

PBD6 210-211

32. (8) This is immune complex-mediated glomeruloncphritis. Thc immune complcxcs activate complcment and

BP6 111-112 PBD6225-226

BP6 B3

PBD6 190-191


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38. (e) With SLE. skin Icsions can be sccn on any area of the body bUI are worsc in sun-exposcd areas. Immunc eomplcxes are lrapped at the cpidcrmal ba<>emcnt mcmbrane. Thc skin with sdcrodcrma shows markcd collagenous fibrosis and no detectable irnmunc complexes. Skin involvcmcnt with Sjogren syndrome and rhcumatoid arthrilis is uncommon. Thc rash of dermalomyosilis has Iymphocytic infillrmes bU! nol usunlly immune eomplex dcposition.

BP6105-106 PBD6222-223

majar fcalures of Reiter syndrome are urethritis, arthritis, and conjunclivitis in young lO middle-aged adults.

BP6115 PBD61251-1252 43. (E) This patient is susceptible 10 bactcrial. fungal, and viral infcctions and most likc1y has SCID. The autosomal reccssive p.:1ttem of inllerilnnce implicates adcnosinc dcaminasc (ADA) dcficiency mthcr ¡han mutalion.'l in the 'Y cha;n of cytokine rcccptors. Low ADA levc1s in the lcukocytcs are diagnostico

BP6 117 PBD6 235 39. (D) This is a major lransfusion rcaetion, resulting from a typc 11 hypcr.rensilivity rcaction. 1ñe paticnt's semm comains naturally oceurring antibodics lo me incompatible donor red blood cells. They altach to lhe recipient red b100d cells and induce complcmcnt activalion thal result.. in genermion of the C5·9 membnllle allack complex. Major transfusion rcaetions are mre, and most rcsult from clerical errors. NK ecll Iysis is secn with ¡mtibody-dc¡x:ndent ccll-ml..x1iatcd cYloloxicity. Antigen-ant.ibody complcx formation is typical for a typc m hy¡x:rscnsitivity rcaction. Masl cells dcgranulme with anligcn attachmcnt lO IgE in typc I hypcrscnsitivity rcactions.

BP690 PBD6 199-200 40. (C) PnelUlIocystis pneumonia is a common finding in pcrsons with AIDS. His low C04 COllnt is characleristic for AIOS. Antineutrophil cyloplas:mic autoantibody (i.c.. CANCA or P-ANCA) can be .'lcen with v3SCulitis. Person.'l with rhcunmloid arthrili.'l do nol have signifieant immunosupprcssion unlcss lhey are Ircaled with highly potenl immunosuppressive drugs such as cyciosporine. The ASO titer i.'l elevated with rhcumatic fever. but tocre is no scrious immunosupprcssion. The antinuclcar antibody test result is positive in a ,'ariel)' of autoimmune discascs. bul lhe decrease in C04 count is no! typical for such conditions.

BP6124-125 PllD6247-248 41. (B) He had SCID. which is treatcd with allogeneic bone marrow transplantalion. The transplantcd stem cells in the bone m¡¡rrow give risc to nomml T nnd B cells. Chcmolhempy is uscd to trc¡¡t malignancies. such m, lym· Ilhoma or 1cukemia. thal are causes for sccondary irnrnunodcficiency. Corticostcroid Iherapy hclps lO alleviatc inflamo mation by rcdueing Iymphocyte funclion aOO numrer. Intravcnous immunoglobulin i.'l helpful in condiLions such as common variable irnmunodcficiency, in which IgG is dcficicnt. Antibiotic thcmpy can aid in trealmcnt of infcettons complicaling immunodcficicncy stalcs bul canllOl treat the undcrlying problcm.

BP6117 PBD6235-236 42. (B) Shc had juvenile rheumatoid arthrilis. About 70% to 90% of ca~s rc.~olve without joillt dcformity. Unlikc rheumatoid ¡¡rthritis, juvenile rheumaloid arthritis reOOs to involve lo....'Cr aOO larger joints, and rheumatoid faclor is oflen abscnt. Syslemic .sclcrosis ís discasc of aduhs mat may have fcalures resembling early rhcumatoid arthritis.. hut joint c\cslructíon is rare. Psorialic arthritis ís a díscasc of adults with features similar lO rhcumatoid arthritis, bul joint invol"ement is more irregular. Ankylosing spoOOylitis in oldcr adults alTccts principally lhe vertebral eolumn. The

44. (D) Strcptococcal M proteins CIOSS-rcact with c<trdiac gl)'coproteins. rc.~ulting in rhcumatic hcan discasc. a form of autoimmunity. Brcakdown of T-ecll anergy usually occurs when locali7.cd lissue damage and infiammation cause up-regulation of costimulmory molcculcs on thc target tissucs. Thi.~ is a pos~ible mechanism of aUloimmunity in the bmin nnd panercatic f3 cens. Polyclonal lymphocYle aetivation may be caused by rnicrobial producls such as endotoxin or bacterial supcrantigens. Rclc.asc of scqucstercd antigens can cause autoimmunity. This mcchanism is likely in autoimmune u"citis; failure of T-cell-mcdiatoo supprcssion has not )'et becn sho.....' ll lO cause any autoimmune discasc. h rcmains a ¡xllcntia} mcchanism.

BP6 100-102 PBD6214-215 45. (C) Virus-infcctcd ccll.'l are rccogni7.cd and kiJIed by c)'tOloxic CD8+ T cens. The T-cell receptor on the CD8 T ccll~ bind~ lo the eomplex of viral pcplidc and MHC Chl.'l.'l I molceulcs on the surface of the inkcted cen. NK cclls also rccognizc MHC cias... I molceulcs with self-pcptides. This rceogniLion inhibits NK ccll killing.

BP6 96 PBD6 206 46. (e) This palient has a drug-induced SLE+like condi+ bon. Procainamide. isoniazid. aOO othcr drugs can cau."C this condition. Tesl rcsults for thc anlinucicar anlibody are ofien posilivc, bul those for the anti-double-slranc\cd DNA are negati\'e. Anli-hislone antibodics are prescnt in many cases. Characteri.'llic signs and .'lymptom.'l of SLE are often laeking. Renal involvCll1cllt is uneonunoll. This condilion rcmits when the patient SIOpS taking toc drug.

PBD6 21B, 224-225 47. (H) He has Goodpasture syndromc. in which there is an antibody directcd against Iype IV collagen in bascmcnt mcmbrancs of glomcruli and in lung. This is a form of type 1I hypcrscnsitivity rcaetion. The antibodics altach to the bascmenl mcmbrane and fix complemcnL thus damaging the glomeruli.

BP6 90 PBD6 201 48. (A) As HIV infcelion proglesscs. there is eontinuing, gradual loss of CD4 cells. Thc stage of dinical AIDS is rcachcd when the pcripheral C04 count drops below 2m ¡..tl. This usually takcs an average of 7 lO 10 years. At this point, the risk for dcvelopment of opportunistic infections aOO neoplasms typical for AJOS incrca'iCS grcatly. 'Thc ex+ tcm of viremia also gi"es an indicalion of thc progrcssion of HIV infcclion. with inerea..ing HIV-I RNA le"e1s as immunologic containmem of HIV fails.

BP6122-124 PBD6245-247


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Chopter 6 49. (L) He has fcatures of X-linked agammaglobulincmia of Bnnon. In lhis condition, B-cell maturation S(ops after the rearrangcment of heavy-chain genes, and light chains are noc produccd. Complete immunoglobulin molcculcs wilh heavy aOO light chains are nor assembled aOO lransported to the cell mcmbraoc. Thc lack of immunoglobulins prcdisposcs the child to recurrent bacterial infeclions. Be· cause T-cell functíon rcmains intact, viral, fungal, aOO protazoal infections are uncommon.

BP6 115-116 PBDó 232-233 50. (8) Amyloidosis is most often causcd by cxcessivc light chain produetíon with plasma ccll dyscra'iias such as multiplc myeloma (AL amyloid). Chronic intlammatory conditions may also rcsult in amyloidosis (AA amyloid) bul OQ( in sccretion of light chains in urine (Le., Bence Joncs protcinuria). Immunoglobulin levels are gencrnlly reduccd in paticnts with common variable immunodcficiency.

BP6 127, 130 PBDó 252-255 51. (O) Pcrivascular accumulation of T cells, pal1icularly CD4 + cells, is typical of dclaycd hypcrsensitivity skin reactions. Systemic anaphylaxis typically occurs wilhin minulCS afler an cncounter with the antigen. Systcmic aoo localized immune complcx diseascs (scmm sickncss and Arthus rcactions) are type ni hy¡x:rscnsitivity reactions; they often demonstr<lte <l va.'iculitis. Gmfl-versus-host discase is ch<lr3.ctcrizcd by epidem1al apoptosis and rash.

BP694-95 PBD6204-205 52. (A) Acule rejcction of kidncy lransplants occurs wccks. months, or evcn ycars aftcr transplantation. It is charactcri7..cd by infiltration wilh CD3+ T cells that inelude the CD4+ and CD8+ subscts. Thcse cells damagc lUbular epithclium by direcl cytoloxicity and by releasc of cytokincs, such as interfcron-')', lhat actívate macrophagcs. 1ñc reaction is callcd acutc cellular rejcction. and il can be readily treatcd wilh cortioosleroids. Intcrstilial and glomerular fibrosis, along wilh blood vcsscl Ihickcning, QCcur in chronic rcjeclion. Fibrinoid necrosis and thrombosis are more typical of hypcmcutc rejcction lhat occurs wilhin minutcs of placement of the lransplam into the n:cipient. Eosinophils aecumulalc in acUle imerstilial nephritis due to dmg rcactions. Matcrial thm stains wilh Congo red and shows grren birefringcnce is amyloid.

BP6 96-9B PBD6207-209 53. (E) She has rhcumatoid arthritis. 1bc pannus of rhcumaloid arthrilis leads lO joint dcstruction aOO ankylosis with markcd deformity. 1bere are fcw other organ-specific Icsioos, though rhcumatoid nodules can be found undcr !he skin ovcr bony promincnccs and in organs such as lung aOO hcart. Renal failurc is more likc!y with SLE. Aortic disscction is more likcly with Rciter syndromc. Ankylosing spondylilis is markcd by kyphosis. Thc risk for malignancíes is increascd with <lutoimmullc disc<lscs. although nol by a grcal degree, and not by much wilh rheumatoid arthritis.

BP6 109- 111

PBDó 1246-1251

54. (C) Shc has Sjogren syndromc. which primarily involvcs salivary aOO lacrimal glands. Anlibodics to SS-B are

DISEMS OF IMMUNrJY

49

fooM in 60-90% of patients. Anti-double-strandcd DNA is a spccific autoantibody fo.- SLE.. Anti-ccntromere antibody is secn in systemic sclcrosis. ScI·70 is a markcr for diffu.sc systemx: sclerosis. Jo-I is a marker for poIym)'C6itis.

BP6 111-112 PBDó 225-226 55. (E) This is a systcmÑ: anaphylactic reaction. a fonn of typc 1 hypcrsensitivity. IgE is bouoo to masl cells, after previous scnsitization. so that a repeat cncounler with the anligen reslllts in mast cell dcgranulation and lhe release of mcdiators, sllch a.~ hislaminc. lhat lead to anaphylaxis. IgE is also important in Illcdiating more localizcd inflammatory reaclions such as allergic rhinilis (i.e., hay fever). Olhcr immunoglobulins do nO( bind so rcadily to mast ccl1s..

BP6 B7-BB PBD6196-19B 56. (D) TIte findings point to the X·linkcd disordcr known as Wiskott·Aldrich syndromc. As wilh many immunOOcficiency disor<Jers.. thcre is an increased risk for Iyrnphoma. Hypocalcemia is seen in noonates with OiGeorge syndrome. Rhcumatoid arthritis can complicate isolated IgA dcficicncy aOO comnlOll variable immunodeficicncy, conditions wilh survival to adulthood. A deficicncy of complemenl componcflt C3 may be complicated by immunc-eomplcx glomendoncphritis. Dcmcntia can be secn with AIOS.

PBD6236 57. (A) Pcrsons infccted wilh HIV .are infecte<! for life. Thcy can pass the virus to othcrs by sexual intercourse evcn if they appear ro be well. 1bc averal:,'C time fo.- Ihe dcvclopmcnt of AlOS after HIV infection is 8 to 10 years.. Serorcvcrsion in HIV infcctioo docs not occur. Scrccning qucstionnaircs aOO scrologie testing can pre\"ent Ihis person from bcing a blood donar. HIV infectioo affeclS mainly CD4 Iymphocytcs, wilh dcclining CD4 counts presaging lhe dcvclopmenl of elinically apparent AJOS. Anlibody ti· ters do not predicl c1inical inness or complications. Progression of HIV diseasc is monitorcd by levels of HIV-I mRNA in the blood and by C04+ ccll counts.

BP6 122-125 PBD6245-24B 58. (C) This is cardiac amyloidosis. At his a!;e, a scnile cardiac amyloidosis, rcsulting from dcposition of Irnnslhyr. ctin, is most likely. AJpha-fetoprotein is secn in fetal life, 001 is best known in adults as a serum tUITlOl" mark.er. Bctarmicrog1obulin contribules to the dcvclopmcnt of amyloidosis associated with long-tenn hctnlXlialysis. Caki· tonin forms the precursor foc amyloid deposited in lhyroid mcdullary carcinomas. Amyloidosis associated wilh plasma ccll dyscrnsias rcsults from light-chain production. AIIllough lhe heart is commonly involvcd in light-ehain amy· loidosis. thc nonnal laboratory values aOO absence of plasma cell oollcctiotls in the marrow arguc against a pla...ma ccU dyscrasia.

BP6127-130 PBD6 252-253, 256 59. (D) He most likely has Bruton agammaglobulinemia, an X-linked primary immunooeficiency marked by recur· rent bacterial infcctions that bcgin .after maternal antibody Ic"c1s diminish. Sclccti"c 19A dcficiency is markcd by a more benign course, with sinopulmonary infections aOO


« I\ot for lale! > « t<e

50

Part I

AIlJI rtpo.llDJ<

! >

GENERAl PATHOlOGV

diarrhca that are not SCVCfC. Deficicncy of C3 is Tare and lcads lO grcatcr numbcrs of infcclions in children and young aduhs. 001 Ginrdin infections are not a fealure of this discasc. Lack of ccll-mcdimcd immullily is more likcly lo be secn with childhood HIV infcctioo. Although somc

paticnL<; with Brulon agammaglobulincmia can dcvclop fcatures of SLE. lIley gcnerally do nol havc a positivc tcst rcsult for antinuclear <lnlibody.

BP6 115 PBD6 232 - 233


< not tor s.u.. ! > < H" .IlIlR npo_ ! >

CHAPTER

7 Neoplasia BP6 Chapter 6 - Neoplasia PBPD6 Chapter 8 - Neoplasia

1. Patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are at greatly increascd risk of dcveloping hepatocellular carcinomas. This predisposition is best explained by

O (A) The consistenl integration of these virusc.-; in the vicinity of protooncogenes

O (B) The ability of these viruses lo cnplure protooncogenes from the host DNA O (C) Virus-induced injul)' to Iiver cells followed by exlensive regeneralion O (O) Tile ability of viral genes to inaclivale Rh and p53 cxpression O (E) The ability of these viruses lo cause immunosuppression of the host 2. A ma-;tcctomy with axillary Iymph node dissect.ion wa-; pcrfonned on a 48-year-old female diagnoscd wilh infiltrming ductal carcinoma of Ihe left breas!. Whieh of the following faclors is most responsiblc for the presence of her Iymph node mcta-aa<;cs?

O (A) Increased laminin recepton; on tumor eells O (B) Presence of keratin in tumor cells O (C) Oiminished apoplosis of tumor ecl1s

O (O) Tumor cell monoclonality O (E) Lymphadenilis 3. A 30-year-old sexually promiscuous fcmale presents with vaginal bleeding and discharge. Colposcopic examinalion reveals an ulccratcd lesion arising from the squamocolumnar junction of the uterine cervix. Biopsy results show an inva<;ive tumor conlaining arcas of squamous epithelium in which pearls of keralin can be seen. In silu hybridiul.lion reveals Ihe presence of human papil10mavirus typc 16 (HPV-16) DNA wilhin the lumor cells. Which of the following molecular abnonnalities in this lumor is most likely relaled lO infection with HPV-161

O (A) Trapping of Ihe ras prolein in a GTP-bound state O (B) Increased expression of laminin receplor genes

O (C) lnability lo rcpair DNA damage O (O) Functional inactivation of the RbJ protein O (E) Increased expression of epidennal growth factor re-

ceplor 4. A 47-year-old maJe has a peripheral blood WBC counl of 167.SOOIML, with matUTe and immature neulrophilic cells predominating. Cytogenctic analysis of cells obtained through bone marrow aspirotion reveals a t(9;22) translocalion. This ha<; resulted in fonnation of a hybrid gene, causing potenl tyrosine kina<;e activily. Which of Ihe following genes was Imnslocaled from chromosome 91

o (A) p53 O (B) Rb

O (C) NF-l

O (O)

K-ras O (E) c-o.hl

5. Right axiUary Iymphadenopathy i8 palpable in a 44year-old femalc on physical examination. These nades are painless but finn. Which of the fol1owing conditions is tllost likely to be preselll?

O (A) Duclal careinoma of Ihe breasl

O O O O

(B) (C) (O) (E)

Acute mastilis with breast abscess Lciomyosarcoma of tbe Ulerus Cerebral glioblasloma multifonne Squamous dysplasia of Ihe larynx

For each of the c1inical histories in questions 6 and 7, malch Ihe most c10sely related leltered environmental agenl thal is causally related lO developmenl of neopJa<;ia in humans: (A) (B) (C) (D) (E) (F) (G) (H) (1) (1) (K) (L)

Arsenic Asbestos Benzcne Beryllium Cadmium Chromium Ethylene oxide Nickel Radon Vinyl chloride Naphthalene Gamma rays

51


<

,,<:o,

COl' ..a.l.. !

52

> < _

POO'

.llJlA 11f.'OJl'*"'" t

>

GENERAL PATHOLOGY

6. A 51-year-old malc who works in a factory producing ptastic pipe expcricnccs wcight I<>ss. nausea. and vomitíng. His scrum alkalinc phosphatase Icvcl is 405 UIL An ~ dominal computed tomography len sean reveals a 12-cm right liver lobe mass. üver biopsy rc"cals an angiosarcoma. ( )

7. For YC3fS. gr.mdfathcr sprayed the orchard each spting with insccticidc. Artcr 20 years, grandfather noticcs a rough, crythcmatous arca of skin on his righl shoulder Ihat bccomcs ulcerated and docs nol hcal. Thc cxciscd Icsion is a squamous cell carcinoma. 1 )

8.

A 30-year-old malc prcscnts with multiplc bcnign subcutaOCQUs lumors Ihat are attachcd to ncn'cs. Funhcr cxamination revcals numcroos pigmcnted skin Icsions. Ophthalmoscopic examination shows hamanomatous nodulcs on the iris. Which of the following mcchanisms of transfonnation is most likcly related 10 the mutation that this patiellt inhcritcd7

O (A) Persistenl activation of lhc ras gene O (B) Increascd production of cpidcrmal grtl\vth factor

O (e) Dccreascd susccptibility to apoptosis

O (O) Impaircd functioning of mismalch rcpair genes O (E) Inactivation of the Rb gene 9. The major mcehanism by which rcpeatcd application of eroton oil (phorbol cster), after a single applieation of a mutagenic agent 00 the skin, promotes carcinogcncsis is

O (A) IndlX:lion of chromosomc breaks O (B) Inhibition of DNA repair O (e) Activatioo of protein kinase C O (O) Activation of cndogcnous viruscs O (E) Amptificalioo of growth faclor ra:eptnr genes JO. An isolalcd polyp is foond by colonoscopy in thc sigmoid colon of a 50-year-old female. 1ñc cxdsed polyp hislologically rcveals wcll-differentiatcd glands with no inva.'iion of Ihc slalk. Whieh 01' Ihc following invesligational rc~rch procedurcs can //lOS! c/early distinguish whclhcr thc polyp rcprcscnls hypcrplasia of Ihc colonic mucosa or a tubular adenoma?

O (A) Histochcmical staining for mudn

O (B) Aow cytomctry to delermine lhe frcqucney of cells in lhe S phasc (growth fraclion)

O

(e) Dctcnnination of cJonalit)' by pattcm of X chromo-

sorne inactivalion O (O) lmmunopcroxidase staining for kera(Ín O (E) Immunopcroxidasc slaining for factor VIU I l. A 66-ycar-old femalc. woo has worked all of hcr ti fe on a small family faml 011 the Kanto plain near Tokyo. has a I~ripheral whilc blood cell (WBC) count of 64.OOOI¡.¡.L. Immunophcnolyping reveals Ihat 90% of thcse WBCs are T Iymphocytcs Ihat are CD4 positivc. Shc has had no previous major illnesscs. Which of thc following viral agents is masl likcly involved in this proccss? O (A) HPV

O (B) Human immunodcficicncy virus typc I (HIV.I)

O (O Epstcin-Barr virus (EBV) O (D) Human T -ecll Iymphotropic virus l)'pe I (HTLV.t) O (E) HBV

12. A 50-year-old fcmate prcscntS with a mass io her righl breasL Physical examination reveals a single ma..... 2 cm in diamcler that is fixed to lhe undcrlying tissocs and three Iymph nodcs are palpablc in the axilla. Thcre is no family history of canccr. Hislologie cxaminatlon of a brea..r biopsy showed a well-diffcrentiated duct.al carcinoma. Dvcr Ihc ncxt 6 months. additional Iymph nodcs bccarnc cnlarged. and mctastascs appcarcd in thc lung. livcr. and brain. Thc patienl dies 9 monlhs after diagnosis. Which of the following molecular abnormalities is masl likcly lO be found in Ihis scuing?

O (A) Inactivation of onc capy of the BRCA-I gcne in fibroblaslS culturcd from thc normal skin O (B) Oclelion of one copy of lhe p53 gcne in a11 cells of the c1inically nonnal parcnt O (C) Amplifiealioo of the c-erb 82 (HER2) gene in breast eanccr cells O (O) Dcletion of the Rb locus in lhe normal somalic cells of Ihc paticnl O (E) Fusion of /x:r and c~ahl gcnes in the canccr cclls I~. Two of fivc childrcn in a family <lre affcetcd by a disordcr thal rcsulL'i in Ihe dcvclopmcnt of multiple skin canccrs Wilh sun cxposurc. Thc parent.. and olhcr rclalivcs are 001 affecled. Which of thc following mcchanisms is mast likely opcrativc lO produce neoplasia in thcse childrcn?

O (A) HPV infcetian O (B) FaiJurc of nlX:lcotide cxcision rcpair of ONA O (C) lngcstion of food contaminalcd with Aspergilllls Jla"/U

O (D) lnactivation of p53 O (E) Chromosomal lranslocation 14. Which of the rollowing conditions is leu.w likely lO givc rise lO <l subscquenl carcinomll in Ihc afTcctcd lissucs'!

O O O O O

(A) (B) (C) (O) (E)

M<lel'Onodular cirrhosis Chronic mrophie gaslritis Oral Icukoplakia Atypical endometrial hypcrplasia Multiple skin ncvi

15. A child is bom with a single functional copy of a tumor- supprcssor gcne. Al thc agc of 5 YC3fS. the rcmain· ing nonnal allcle is losr through mutalion. As a rcsull t.hc ability lO control lhc transition from G 1 lO lhe S phase of ccll cycle is losl. Which of lbe following ncopla...ms is most likcly 10 arisc by means of this mcchanism?

O O O O O

(A) (B) (C) (O) (E)

Retinoblastoma Brcast carcinoma Adcnocarcinoma of colon Cerebral ast.rocyloma Chronic mycloid lcukemia

16. A biopsy of an enlarged, nontendcr poslerior cervical I)'mph nodc from a 66-year-old femalc rcveals cffaccmcnt


< I>ot [or 5a..le! > < He .IlJIA "PO.Il""'" ! >

Chapter 7

of Ihe nodal architeclurc by a monomorphous population uf large cells with large, dark bluc nuclei and seant cytoplmim. The pcripheral blood SOlear and bone marrow biopsy are normal. This process is most likcly to be a

O (A) Lymphangioma

O (B) Reaclive hypcrplasia O (e) Lymphoma O (D) Mycloma O (E) Lcukemia

NEOPLASIA

53

20.

A 46-year-old malc is foum.l to have an cnlargcd. nontender supmclavicular Iymph node palpable on physical cxaminatlon. The Iymph nodc is cxeiscd and found lO be 2 cm in diameter. Histologically, the nodal archilecluTC is cfTaccd by a 1110nomorphous population of small Iymphocytes. Which of lhe fol.lowing proccdures is best lO confinn Ihat he has a ma.lignancy?

O (A) Peripheral white blood ecll count and differemial cell counl

O (B) Row cytomelry of nodal tissue for DNA content O (e) Eleclron micrrn;copy to determine ccllular uhrastructure

O (U) Southern blot ana.lysis to demonslrate monoclonality O (E) Delerminalion of thc serum lactate dchydrogenase levcl 21. Which of lhe fol.lowing principies of earcinogenesis is best iUuslralcd by thc sludy of molecular alterations that QCcur during lhc evolution of a sporadic eolonic adcnoma inlo an invasive carcinoma?

O (A) Protooncogencs can be activatcd by chromosomal translocation.

O (B) Malignanl tmnsfonnation involves accumulalion of

17. Thc high-power microseopic appcarance of a neoplmim from a 58-year-old femalc is shown in the figure. AII areas of lhe tumOr have similar morphology. This neoplasm is besl dcscribcd as a(an)

O (A) Adcnoma O (B) Wcll-differcnliated adenocarcinoma O (C) Squamous cell carcinoma

O (D) Leiomyoma O (E) Anaplastic carcinoma 18. A 59-year-old malc rccently nOliced some blood in his urine. A eystoseopy rcveals a 4-em exophytic mass involving !he rigbt bladder mucosa. A radical cystectomy is pcrformed. Examination of lhe cxeiscd spccimen shows lhal he has a grade IV transitional ecll carcinoma lhat ha~ infiltrated through the bladder wall. Whieh of lhe following stalements rcgarding these findings is mosl appropriale?

O O O O O

(A) This neoplasm is a metastasis. (B) He has a poorly differentiatcd neoplasm. (e) A parancoplastic s)'ndrome is likcly. (O) The slage of lhis ncoplasm is low. (E) He is probably cured of his cancer.

19. Which of Ihe following diagnostic scrcening lcchniques uscd in health eare has had the greatcst impact on rcduction in cancer dcalhs in devdopcd nalions?

mutalions in protooncogenes and tumor supprcssor gcnes in a step-wise fashion. O (e) EXlensive regeneration of tissucs increases Ihe risk of canccr-causing nmtations. O (D) Inheritcd dcfccts in DNA rcpair increase lhe susccptibililY lo Ihc devclopment of cancers. O (E) Overexprc.<¡sion of growlh factor receplor genes is associaled with poor prognosis. For cach of the patient histories in qucstions 22 through 26, match lhe most .likc.ly genc that is affcctcd during the ncoplmitie process: (A) p53 (ONA damage response gene) (8) APC (tumor suppressor gene) (e) IL-2 (growth factor gene) (D) L)'1l (tyrosine kinasc gene) (E) K-ras (GTP-binding protcin genc) (F) ,,16 (cyclin-depcndcnt kina'le inhibitor. .lNK4a) (G) e·m)'c (lranscriplion factor gene) (H) bcl-2 (anli-apoptosis gene) (1) EGF (epidcnnal growlh factor gene) (J) bd-I (cyclin gene) (K) NF-I (GPTase-activaling protein) (L) N-myc (transcriptioll faclor gene) (M) BRCA-I (DNA repair gene) (N) hst-I (fibroblast growth factor gene) (O) c-ah 82 (growth faclor receptor gene)

O (A) Chcsl radiograph

22. A patient is diagnoscd with follicular Iymphoma. Karyotypic analysis rcveals a chromosomal lranslocation. t(l4:18). involving the imllmnoglobulin heavy chain gene. ( )

O (B) 51001 guaiac O (e) Pap SOlear O (O) Scrum eareinocmbryonic antigen assay O (E) Urinalysis

23. A patient prcscnts wilh cough am.l hemoptysis (i.c., blood in spulum). A lung biopsy reveals small eell lung carcinoma. Family hislory reveals thrce firsl-degree maler-


< not COl' lMl..le' > < ...

54

Port I

.llJl~

n¡l(l.ll""'" ! >

GENERAl PATHOlOGY

24. A 5-}'car--old child presenls with an abdominal mass that i... diagnoscd as ncuroblastoma. C}'logcllelic anal}'si!l of lumor cell.. shows man}' double minules and homogencously staining rcgiolls. ( )

29. A 22-year-old female won.:s as a sccrctary for an accounling firmo She has a palpable oOOu1c in Ihc righ! lobe of hcr lhyroid gland. A finc-nccdlc aspirnte of the nodule reveals cclls consislent wilh a carcinoma of lhe thyroid. No ottlcr family membcrs are affccted by this disordcr. Which or the following would )'00 considcr rele.vanl in her pa.~1 history?

25. A 26-year-old female prcscnts wilh carcinoma of !he brcas\. Her 30-year-old sisler was rcccntly diagnoscd with ovarian eancer, and her maternal aUTlt had a masleclorn}' 3 yeal''- earlicr for duclal carcinoma of lhe breas!. l )

O (B) Ataxia telangicclasia O CC) Radiation Iherapy in childhood O (O) Blunl trauma from a fall

nal reialives who dcvc10p00 Icukemia. sarcoma. aOO l.:an:inoma befare thc agc of 40. ( )

26. A 20-year-old mate prcscnls with a raiSt.'d. irregular pigmenlcd lesion on his forearm. Biopsy rcvcals a dccply infiltral;ng rnalignanl mclanoma. Family hislory rcvcals that his palcrnal uncle dicd uf melastaric mclanoma thar spread lO Ihc li\'cr after cxcision of a primary Icsion on thc rool. Hil' grnndfather rcquircd enucleatioo or the lert eye bccausc of a ··dan.: brown" Illi!SS in lhe eyeball. ( )

O (A) Chronic alcoholism

O (E) Exposlll'e lo arsenic compounds

30. A Pap smcar reveals the prescncc of scvcre ccrvical dysplasia in a 35-year-old fcmale. Which of Ihc foUowing viruses binds tO pRb lO inacasc Ihc risk rOl' Ihis lesion'!

o (A) EBV

O (B) HBV O (C) HlV O (O) Cytomcl,!-alovirus O (E) HPV 31. A 62-year-old male w;lh a hislory of chronic alcoho/ism has an c1evatcd scrum a-fctoprolcín levc!. Thcre are no masses 01' Iymphadcnopathy palp:\ble anywhcrc on physical examination. A slool guaiac test is ncgative. Which of thc following ncoplasms is mOSI likcly?

O CA) Proslalic adenocardnoma O (B) Pulmonary squamous cell carcinoma O (C) Multiplc myclolna O (O) Pancrcalic adcnocarcinoma O (E) Hepaloccllular carcinoma

27. The mcdium-power magnificalion microscopic appcllrance of a lesion from a 39-year-old female is shOWTl. She had an abnormal Pap SOlear. and a cervical biopsy of a I-cm. red. slightly raised Icsion on the anterior ectoccrvix al 2 o'clock was performcd. Which of Ihe fol!owing slatemenls best characterizes hcr condition?

o (A) O (B) O CCl O (O) O lE)

A primary sile should be sooght. This is a high-gradc lesion. 1b= cell of origin i5 a fibrobla.'it. A chCSI radiogrnph will show oOOulc.,. Local excision will be curntive.

32. A 49-year-old tnalc has an cpisodc of hcmoplysis. A Chesl rndiograph rcveals a 5-cm ril,!-hl uppcr labe lung mass. A finc-nccdle aspiratc of Ihis ma<;s yiclds cclls consistent with small cell anaplastic carcinoma. On careful cxam;l1ation, lhe patient is found 10 hllve puffiness of Ihe facc. sorne pedal cdema. aud systolic h}'pertcnsion. Abone scan shows no metastascs. ImmunohiSlochemical staining of thc tumor cells is Iikcly lo be positivc for which of ¡he following? O (A) Parathyroid hormonc W11-I)-rclated prOlein

O (B) Erythropoietin O (C) CorticOlropin O (O) Lnsulin O (E) Gastrin

28. An immunopcroxidasc stain for lhe proteasc cathcpsin O is pcrfo.-mcd on (he microscopic tissue scclion from a breasl carcinoma in a 61-ycar-old female. Therc is proIlounced c}'loplasmic staining in lhe lumor cclls. The prcscncc of Ihis markcr is most likcly to prcdicl lumOr;

33. A routine checkup fo.- a 4O-)'car-old male includcd a slool guaiac Ic."l. which was posiLive. A sigmoidoscopy rcvealed a 1.5-cm. drcumscribcd. pcdunculatcd mass on a short stalk located in the uppcr rectum. Thc bes\ lerm for Ihis lc..,iol1 is

O O O O

O (A) O (B) O (O O (O)

(A) (B) (C) (O) O (E)

Angiogenesis Invasivencss Oiffcrcnlialion Helcrogeneity Ancuploidy

Adenoma Hamartoma Sarcoma Choristolna O (E) Ncvus


ChOpler 7

NEOPlASIA

55

34. A 40-year-old male devclops generalizcd Iymph nade enlargcmenl and hepalosplenomcgaly. Lymph node biopsy rcvcals a malignanl lumor of Iymphoid a:lIs. ImmullOpCroxidase slaining of lhe tumor ce))s with antibody lO bel-2 is positi"c in thc Iymphoc)'lic cell nudci. By which of thc fol1owing mcchanisms has mis Iymphoma occurred? O (A) Incrcascd tyrosine kinase activilY

O (8) Lack of apoptosis O (q Gene amplificatiorul O (O) Rcdoccd DNA rcpair O (E) l....oss of ccll cyele inhibilion

35. A 70-year-old female had a 4-monlh hislory of wcight loss and incrcasing generali7.cd icleros. An abdominal cr sean revea1cd a mass in the head of the pancrcas. Molecular analysis rcvea1cd Ihal Ihe Ilcopla..lic cclls showed conlinucd aClivaliOIl of cyloplasmic kinases bccause a mUlatiOI1 grcaLly rcduccd Ihe ability lO hydrolyzc GTP a(ter growth faclor stimulatiOI1. Which of Ihe following oncogencs is most likcly lO be involved in this proccss? O O O O

(A) II1Yc (B) (Ibl (C) ras (D) /U!/I O (El si.t

For cach of lhe palien! hislories in q\.lQilions 36 through 38. match the most dosely associated Ictlered ncoplasm: (A) Adcnocarcinoma (B) Adenoma

(q Carcinoma in situ (D) Fibroadcnoma (E) Fibroma (F) Glioma

(G) Hamartoma (H) Hcmangioma (1) Hepaloccllular carcinoma (1) Lciomyoma (K) Lipoma (L) Lymphoma (M) Mcl:moma (N) MCl1ingioma (O) Mcsothelioma (P) Nevus (Q) Oslcosateoma (R) Renal ccll carcinoma (5) Rhabdom)'osarr:oma (1) Small cell anaplastic carcinoma (O) Tcratoma

38. A 32-year-old female has had some duB pclvie pain for the last 2 months. An abdominal ultra"Ound revcals a ma~s involving the righl ovary lhal is 8 cm in diamcter. The ma<;s is surgically CXciSL-d. The surface of the mass is smooth. and it is nOl adhercnt to sUlTOUnding pclvic SlrucIUfCS. Grossly. thc mass is secn lO be cystic and fillcd wilh hair. Microscopically. thcre is squamous epithelium, taU columnar glandular epithclium. cartilagc. and fibrous coo) nccti\'c tissuc. ( 39. A palicnl wim malignant mclanoma is treated by infusion of autologous CD8+ T cclls lhal are known lo kili his mclanoma cclls bul nOl nonnal cclls. 1ñc target antigcn rccognizcd by Ihesc CDR+ T cells is masl likely composcd

or

O (A) Class 1 majar hislocompatibility complex (MHC) molccules plus a pcptide produccd by nonnal melanocytes and mclanoma cclls O (B) Cla"li I MHC molcculcs plus a pcplidc derivcd from carcinocmbryonic allligcn O (e) Class 1I MHC molcculcs plus a pcplidc dcrivcd from rnclanoma cclls O (Dl Class I MHC molcculc.s plus a pcplide produced by mclanoma cclls O (E) A pcptidc sccreled by mclanoma cells and prescntcd by laminin rcccplOrs on melanoma cells

40. Several episodes of hematuria in lhe previoos wcek ....ocre llOliccd by a 62-year-old male. His urologisl pcrfonncd a cystoscopy and obscrvcd a 4-cm scssi1e mass wilh a nodular. ulceralcd surfacc in lhe dome of the bladder. How would yoo besl describe mis Icsion?

O (Al Papilloma 36. A 23-year-old female has a O.S-cm-<l.iamcler. nanlender. raiscd nodulc on the skin of hcr uppcr chest. This nadule has a smooth surfacc and is dark red. Shc stales that thc nodulc ha~ becn prescnt for many ycars and has nol changed in size. ( ) 37. A 29·ycar-old female has a cervical biopsy aftcr a Pap smear tha! Is abnonnal. Shc is asymptomatic. She has a hislory 01' multiple sexual partncrs. The microscopic appcar¡lOCe of the biopsy is shown in the figure. ( )

O (B) O (e) O (D) O (E)

Carcinoma Adenoma Sarcoma Fibroma

41. A 66·ycar-old malc \Vith chronic cough aOO recenl hcmoplysis ha~ a chest radiograph thm shows a 6-cm rig.ht lung ma..s. A sputum cytologic analysis rcvcals cclls consistenl wilh squamous cell carcinoma. Whcre are melaslases from Ihis Ilcoplasm mosl likcly lo be found?


« not for uJel :> « Ke AIIR npoJl""'" I :>

56

o (A¡

Porl 1

GENERAL PATHOlOGV

Chesl waJ] musdc

years ago. whm would of dcalh?

O (B) Splcnic rctI pulp O (C) Hilar Iymph nodcs

re Ihe

loosl likcly undcrlying C¡¡use

O (A) Kaposi sarcomll of lhe ler.

O (D) Venebrnl booe marrow

O (B) Inliltrming duelal carcinoma of breasl

O (E) Cercbrum

O (O Atlcnocarcinoma of lhe lung O (1) SqualTlOU~ ccll carcinoma of scrolum O (E) ('}.;Icosarcoma of lhe libi"

Which of lhe following principies of carcil'lOgcllt$is is by lhe sludy uf human.. wilh hcretlilary nonpul)'f'lOI'is colon canccr (HNPCCl?

4b.

bes/ mllsln/lel/

O (A) Tumor initialors are mUlagenic. O (13) Tumor prOlnolcrs ilKlucc prolifcrmion.

O CC) Many onco!,enes are aClivmcd by Iranslocations. O (D) Irlllbilily lo repair DNA prooisposcs lo devclopmclll of C¡lnccr. O (E) C:\rcinogenesis is a mullislcp proccss.

42. 1ñe H\'er m aulopsy oC a 69-yc.ar-okJ Ccm.."Ile is shown. Which oC lhe CoIlowing slalcmcnt.s bc."1 characlcrizes Ihis proccs... ? O (A) A li\'er biopsy would havc shown a dy...plasia. O (B) ""is is a multiCocal hcpalic adenoma. O (e) A hepmoccllular carcinoma h.."IS in\'¡llJctI locally. O (D) Colonic adenocarcinoma wilh meL."l5Iasc.s was

47. A 38-yc1.Ir-old female presenl.~ wilh abdominal dislenlion. amI a (T sean demonSlflllc.~ bowcl obslruclion wilh ¡l 6-cm Ill11SS in lhe jcjunum. A Burkiu Iymphoma of lhe Sm¡111 bowe1 is rcscc1et1.. mxl ¡¡ l)Or1ion of lhe lumor senl for now cylomelry analysis shows a high S plw.sc. MUlation.."I1 aClivalion of which of lhe following nudcar oncogencs is likcl)' lo be pre.<;ent in Ihis lumor? O (A) c-l'rb 82 0(13) p53 O (e) n/S 0(1))

myc

O (E) APC

presenl. O (E) Rcscclion or lhese le..ions should hl.\\'C been done.

43. A surgcon is perfonning :1 partial colcclomy on a 75ycar-oh.l CcmaJc who has a 5-cm scssilc m:L~.~ in lhe lower sigmoiJ colon. Which of Ihc following Icchlliqucs pcrformet.l durillg surgcry besl ¡¡ids Ihe surgcon in dCICnllilling wl1cll1cr Ihc rCSCClion is <ldCqU¡lIC lO reducc the prob<lbililY of a rCCl1n'cllcc'!

O (A) Fine-llced1c l.\~pimliuo O (B) Scnll11 carcillocmbryonic llnligell aSS<ly

O ln

)'ollr 4O-ye..'lf-()ld focondilions. Allhough of Ihe fol1owing prcincrease:.' her risk for

O (A) Fibroadcnoma of Ihc bre¡¡sl

O ~B) Bronchial :L,>lhma O (C) Dcgcnermive oSlcoanhrilis 0(1)) Chronic IIlccrmive colilis O (E) Lci01l1)'omas of Ihc lllerus

Frotcn scclion

O (D) Elcctron mieroscopy

O (E) Flow cylnmclry

44. A 12-cm mass is foond in Ihc uterinc wall of <l 60yc¡¡r-old fcnll.de who Ill.l.s .smukctl cigarcltes lor mosl of hcr life. ""is 1Tli.ISS on rcmo\'al ha.. Ihe microsoopic appearancc of a wcll-diffcrenti<llet.l Iciomyos.."IJComa. A )'CM laler. a chesl radiogmph rc\'cals a km righl Iowcr Illng nodule. A biOPSy of a lung nudule revcólls a poorly differenlialcd Sóltcoma. 1llc.'iC findings are besl cxplaincd by

49. A 33~year-old fem<lle h¡L,> ¡l rollline physic<ll cxaminalio!l. 1ñere are no <lbnorm¡¡1 findings. As pan of lhe peh'ic examin¡uion. a Pap snlC<"Ir is obtaincd. C)'lologically. Ihc ccUs oblaincd on lhe smcar fmm lhe ccn'ix demonslmlc SC\·crc epithclial dy.splasia. Whal woukl )'00 advisc lhis pnlienl rcgnrding lhe Pap sn'lC.."It diagnosis?

O (A) This lcsioll could progress lO inva..i\'c cervical cnrcinol1l.."1. O (B) An ovarian Ictaloma is presenl.

O {C) lñcre has bcen regres...ion of a ccrvical carcinoma. O (D) Anlibiocic lhempy will curc lhe lesiono O (E) YOllr rema[e re!alivcs are al risk for lhe s.."Illle prob-

O

(A) Dc\'CIopmcnl of a sccood primary Ilcoplasm O (B) Inhcrilancc of a deJcclivc Rb gcne O (e) Conlillocd smoking by lhe palicnl

O (D) Loss of an oncogcnc O (E) Mclasla.~is fmm an agF.rcssivc sutx:lone of Ihc mnry lumor

48. In laking a hislOf)'. )'OU r«onl malc's pre\'iousl)' diagnoscd lllcdicóll she currcn!ly is asymplolllalic, which existing condilions is most likcly lo c:mecr?

lcm. pri~

45. If you wcre Sir Percívlll POli. signing !he death ecnifiCHle f(Jl" Ben Ihe chimncy swccp in Lolldon more Ihan 200

50. A chungc m bowcl habils promplcd a 53-)'c<lr-old femalc lO scc hcr physidan. woo fOllnd lh<ll shc ha~ n posili\'e lc,o;l rcslllt for slool gllainc. 1\ colonoscopy rc\'cnlcd l.\ )-Clll scssilc mass in Ihe cecum. A biopsy of Ihis mass


'" not rOl' .ale! > '" He .llJl~ npo,!llUlll ! >

Chopter 7

t1emonslrated a ITlOderalely differenlialed adenocarcinoma lhal was confinel.l lO lhe mucosa. How should a surgeon deal wilh Ihis informalion1

O (A) Perfonn a limiled excision lo "shell oul" the lesion from its sunounl.ling capsule

O (O) Assume Ihat trus represenls a rnelastasis and search for a primary elsewhere (C) Resecl the lumor 'lIld sorne of lhe nomal SUlTOund· ing tissue O (O) Remove Ihe enlire colon lO prevem a reCUITence O (E) Observe Ihe lesion for furthcr incre:1sc in Si7..e

O

51. An 18-year-okl hoy has had muhiple basal cell anl.! squamous cell carcinOlllllS of his sun-exposed sldn on Ihe Imnk and exlremilies. He also has a sisler who is similarly affecled. This disease is mosl like1y lO be lhe result of l.Iefeclive genes lhat

O (A) Conlrol apoplosis O (O) Regulate repair of dam:lged ONA O (O Encocle Irnnscriplion faclors

O (O) Inhibil the cell cycle O (E) Regulale secrelion of growth fllclors 52. A family hislory of colon cancer is c1icitcd fmm a 36-yellr-old male. Based on Ihis hislor)', a scrcening colonoseopy is performed. and Ihe 'lseending colon ;s found to conlain five polyps from 0.5 lo 2 cm in cliameler. They are excised and examinecl microscopically. The 2-cm polyp is found lO llave a focus of adenocarcinoma. Inherilance of which of the following lypes of genes is mosl likely lO be involved in Ihe eausation of lhis lumor?

O (A) Growth faclor rteepC.ors O (B) Growlh faetors O (O ONA mismalch repair O (O) C}'Clins O (E) Inhibitors of apoptosis 53. A 56-year-old fcmnle hils a granulosa-ll1eca cell lllmor of Ihe lefl OVlIry prodl1dng excessive eslmgell. Shc also has '1l1 eooomelrial carcinoma. The coexistcnce of tbese lumon; is an example of

O (A) PromotiOIl of carcinogenesis O (B) Tumor helerogeneily O (O A parnneoplaslic syndrorne 0(1)) Genelic susceplibililY lo tumongenesis O (E) MUl.,tion of a tumor suppressor gene

A 67-year-old male has had a chronic cough foc sev· eral months. A Chesl rncliogmph reveals a right lung mass. aoo a fine-needle aspirate or lhe mass shows cells consislem wilh squamous <:en carcinoma. If slaging of Ihis neoplasm is dcnoled as 1'2 NI MI, which or lhe rollowing slalements is most accurale?

54.

cr

O (A) A he.\d sean shows a 2-cm right parietal mass. O (B) Serum chemistry reveals an elevatcd corticotropin leve!' O (O The mass t..,cl inliitratcd [he che.-.1 wall. O (O) This cancer is poorly dirferentiate<l. O (E) The lumor is obslrucling lhe lef! mainstcm bronchus.

NEOPlAStA

57

55. A 33-year-old male has haJ occ."lsionai headaches for lhe pasl 3 monlhs. He suddenly has a generalizetl seizure. A head cr sean reveals a perivcntricular 3-cm mass in lhe region of !he right lhalamus. A stereotactic biopsy of the mass yields cells diagnoslic for a 0-«11 malignanl Iyrnphoma. Which or lhe followillg underlying clisease.... is he mosl I¡kely to have?

O (A) O (B) O (C) O (D) O (E)

Diabeles mellitus Acquirecl immunodeficiency syndrome (AlDS) Hypenension Multiple sclerosis Tuberculosis

56. A scrum chcmistry panel on a 76-year-old ma1c reveals an alkaline phosphatase level of 290 U/L wilh no ()(her abnonnalilies identified. After a serum proslale-spocific antigen leve! is found lO be ekvaled. he has a prostate needle bi.opsy !hal reveals a modemlely differelltiated adenocarcinoma Which of lhe following mechanisms best acooums for these fmdings?

O (A) O (B) O (C) O (D) O (E)

Tumor eXlcnsion lO rectUIll Pamneoplnslic syndrome High tumor grade Melasla<;es lO vcrtebrae Tumor allgiogenesis

For coch of the slatemcnts in questions 57 and 58, rn:ltch the lTlOSl close!y associated letlered malignancy: (A) (8) (Q (O) (E) (F) (G) (H) (1} (J) (K) (L)

Angiosarooma of liver Oreast carcinoma Bronchogenic carcinoma Cervical squamous cell carcinoma Colonic atIenocarcinoma Gastric adenocarci noma Glioma of brain lcukemia Lymphoma of Iymph noocs Melanoma of lhe skin P'dIlcreatic lldenocarcinoma Prostalic aJenocarcinoma

57. In lhe lasl half of lhe 20th cen!UI)'. the number or l.Iealhs from Ihis cancer increased marketlly in l.Ievelopecl Il:Jlions. In 1998, more Ihan 30% of male cancer clealhs 'Uld more tban 24% of female cancer deaths wcre causal by lhis neoplasm. ( ) 58. 1lle incil.lence of lhis ncopl.a.<;m has been decreasing in <kvelopcd nations in lhe latter half of the 21).h century, des· pite lhe :.Ibsence of wil.lesprc:.K1 screening programs. ( )

59.

A 1.2-em. clarkly pigmented skin lesion is excisecl from lhe dorsum of lhc right hancl of a 42-year-old male. who notices that (he lesion had become larger cluring lhe previous monlh. Microscopically, a malignanl melanom¡l is presenl. Which of lhe following fdcton; presenls the gremCS! risk for development of tbis neoplasm?

O (A) Smoking O (B) Uhrnviolct rnc.Ii'llion O (O Chernothernpy


< not for nle! > <

58

Port 1

He

.nn_

11J>O,1liUU'l

! >

GENERAl PAlHOlOGV

0(0) A .. besl~ cxpusure O (E) Allergy to lalcx

ANSWERS 1. (C) Although Ihc HBV and HCV genomcs do nOl ell(;ode for <llly Imllsfonnillg prolcillS. Ihe rcgellcraüllg hepalocyles are morc likcly lo dc\'c1op lIlulaliolls such as in;lelivalion of 1,53, HBV docs nol havc ¡¡ consistenl sile of inlcgnllion in Ihc I¡ver ecll nuclei. oor docs il eontain viral oncogenes. Many DNA vinlses. such as HPV. ilkletiV:.IIC lumor supprcssor gcnes. bul lhere is no coovincing cvidencc 111.1.1 HBV or HCV can bind lo p53 or Rb proleins.

BP6167

PBD6 313-314

2. (A) Se\'eral palhologic mechanism.. play a role in devclopmcm of lumor rnctast.1.scs. Thc tumor eclls musl fir'M bccomc disoohesivc and dclaeh from lhc primmy sile and Ihcn allach clscwhcrc lo beeome melasl¡L'iCS, Tumor eclls tend lo havc Ill<l!lY more Inminin receplors llmn nomwl cclls. allowing Ihcm lo more readily ¡Iullch lo bascmclll mClllbr:llles nI disllllll ...iles. A redllclioll in npoplosis al10ws w'c;ller prolifcralion bUI not nccessarily rnelashl..c.... Mono.. c10nalilY is a fe¡\lure of neoplasia. bUI fllr1hcr tumor helerogcocilY hclps ¡!lcrensc (hc ehanec for lllCl:lSl<l<;C.S lO occur. Inf1ammalion prohably docs nol playa m.1.jor role in me.. ta...lnsis. Keratin is a marker of epilhclial difTerentialion. not mclaslalie ability.

BP6161-162 PB06302-304 3. (D) Thc oncogenie potcntial of HI>V. a sc:xually Irans.. mis...ible agcnt, is relmcd lo produCls of Iwo early viral gencs-E6 and E7. E7 biOOs lo Rb prolcin lo COIUSC: displneemcnl of normally SCl.jucslcred lranscription faclors, 'Iltis nulJitics tumor suppressor <lelivily of Ihe Rb protcin. 1::6 binds lo and inaeliv¡llCS Ihc p53 gcne produel. Trappillg of GTP-boulld ras prolcin e¡lIl occur in Illany lUlllors bUl is no\ rclalcd lo HPV infCClion. Lamillin receptor cxprcssion (;orn=lalcs wilh mela...I<llie poten!;al of a malignanl neoplasm. Incre.1..'iCtJ epidcrmal growlh faclor (EGF) receplor exprcss.iOIl is a femure lOCCn in n....1.ny pulmonary squamous cell carcinom,;ls. uOO Ihc relmoo c-eriJ 82 (HER2) receptor is scen in somc breasl. carcinomas.

BP6 167 P606311 4, (E) Ths is Ihe PhilaJc1phia chroll1Q'iome of chronic lllyc1ogenOlL" lcukcmia. 'Iñc 1(9;22) eauses e-ah! on chroIllOroffiC 9 lO fuse with ba on chromosome 22. 80th /153 and RIJ are IUmor suppressor genes. ¡¡nd loss of both allcles is necded lo promote ccll prolircrmion. 'n1C NF-\ gcnc is a signal Imnsdueer sccn in schw<llmomas. '111C f'{/S oneogellcs are illvolvcd wilh GTP bindillg alld bccOlllC :lclivnlcd fmm poinl mutmions,

BP6150-151

PBD6 2B5-2B6

5. (A) Lymph.1.tie sprcad. especially lO regio.....1.1 Iymph ncxles draining fmm lhe primary site. is Iypieal for a carcinoma. Infcction fmm a brc.1.SI absce.....~ can sprcaJ to thc

Iymph nodcs. bul lhe resulting nod.1.1 enlar!.'Cment is Iypieally associatoo wilh p.1.in-a cardinal sign of acule inf1ammalion. Sarcomas uncommonly melaslasize lo Iymph nodcs. Cenlral ncrvous syslcm (CNS) 1n.1.lignancics rarely IllClaslasize oUL..idc of thc C1'\S. Dysplasias do nol metastasizc. bccausc lhey are nOl malignancics.

BP6 139- 142 PB062tf1-272 6. (J) Vinyl ehloridc is a rarc causc of liver C¡lllCer. I-Iowe\'er. Ihis cHusal rclationship was ensy lo dcmonslmle. beemlSc hepmie angios<lrcorn<l is a r;lre noopl<l~ll1.

BP6 144 PBD6 7. (A) Arscnic cnn cause skin cancer. Howcver, Icad arscomc has not bcell in widespread use foc" years. and oceu· pmional ~1.fely mea...urcs ha\'e rcdocoo risk... lO workers from use of ehcmicals in agriculturc ;100 ioollstry.

BP6 144 PB06 274. 309 8. (A) This pntient h.1..S c1inical fc.1.tures of oeurofibron....1.losis type l. 'Iñc Nf-I gene cncodes a GTPasc-oclivating prolcin Ihal faeilitmes lhe con\'crsion of active (GTPbouOO) rtI.\' lo inaeli\'c (GDI'-bound) rt/.\'. Loss 01' NF-I prevents sl1ch eonversion alld Iraps ms in lhe active signallrallsmiuing stage. AI1 olhcr genes are ¡lIso invol\'ed in e¡lrcinogenesis, H1th(lllgh in diffcrelll lumors.

BP6 153 PBD6 2930 (e) Phorbol eslers cause tumor pmmolion by aeli"nl· ing prolein killase C. 'nlis enzymc phosphorylales seveml suoormes in sign:ll lrnnsduetion palhways. including Ihose aclivatcd by growlh factors. and Ihe cells divide. Forccd cel1 di\'ision prcdisposcs lhe accullllllmion of mUlmiolls in cclls previously d.un..1.gcd by exposurc lO a Illulagellic agcnl (Le.• initialor).

IJ.

BP6 165 PB06 309 10. (C) A lrut' neophL..m is ¡¡ monoclonal prolifernl;oll of eclls. whereas a reactive prolifcration of cdls is no! monoclona!. Rcneti\'e and lleoplaslÍc ecllular proliferalions m;IY havc similM hislochclllic¡ll alld immullohislochcmic¡,1 sl;lining patlerns bm¡c¡J on Ihe typc of cel1s Ihal are prcscnl. Row eytolllclry is good at iOOie¡¡ting Ihe ONA content. ancuploidy, and gro\\1h fraelioo bU! docs 001 indieatc clonalily.

BP6 145-146 PBD6 277 11. (D) Shc has :t T -ceU lcukcmia, which dcvclops in ¡¡ppmximatcly 1% of pcrsons infectcd \Vilh HTLV-1. HI'V is besl koown for eausing squamol.ls epithclial dysplasias aOO earcinocna.... HIV·I infcetion is lhe eause for AIOS. EBV infoclion is associalOO with a vunely of cancers, including Burkill Iymphoma aOO na.'Klpharyngenl carcinoma, HBV infCClion mny rcsult in heP:11ic eirrhosis. in whieh hepalOCclll1l;lf enreinoma may arise.

BP6 166 PB06314 12. (C) Increnscd expression of c-e,.b 1J2 (HER-2) enn be dclcelcd immunohislochemieally in Ihe biopsy specinlClI. Up lO a third of brensl canccrs Illay dcmonslrate Ihis change. Such amplirtcation is as.'iOCialcd with a poorer prognosis. Dclcetion of a spccifie gene produel io the lis-


< not for u.lel > < He Mil

npo.Ila>I>l I

>

Chopler 7

sue has value for clelerminalion of prognosis. BRCA~I ancl p53 nlulalions, if inherilcd in lhe gerlll line. can predispose lO bre:'\!il cancer aOO olher lumors. Ho\\:ever. wilh BRCA-\ lbefe is family hislory of breast cancer, aOO p53 mulalion prelIisposes 10 many Iypes of cancers. An inheritetl clelelion of Rb gene preilisposes lo reliooblaSlOma. The bcr-c-abl fusion produet is seen in chronie nl)'eloicl leukemia. It rcsults from 1(9;22). BP6151 PBD6266 13. (8) llleSe ehildren have lhe alllosom.,1 recessive conclition known as xerodenna pigmcnlosum (XP). Affcetcd persons have extreme photosensilivilY, wilh a 200Q-fold increase in lhe risk for skin canccrs. "Ole DNA clamage is initiatetl by exposlIre lO ultrnviolel light, bul nucleolicle excision repair cannot occur nonnally in XP. HPV ís a seXtl:llly Imnsmillecl agenl Ihat is associlllcd wilh clevclopmenl of genital squamous cell carcinomas. The A.wergillus ftavus <1Il moldy peanuls and olher f<xxls produces Ihe polem hepalic carcillogcn aflaloxin DI. In,lclivalion of lhe /)53 lumor supprcssor gene is found in many spomdic 1m· man callcers 'lIld in some familial cancers, bUl the Cancers are not limiloo lO the skin. Chromosomal Imllslocations are oflen involvetl in clevelopmenl of hemalologic malignancies, allhough llOl oflen in skin canccrs.

BP6 165 PBD6 310 14. (E) 1ñere are preneoplaslic conditions from which cancers are more likely 10 arise. Macronoclular cirrhosis fmm he~lilis B infeaion can give rise lo hepalocellular carcinoma. G.'\Stric adenocarcinoma can arise in chronic alrophic gaslrilis. Or.ll squamOllS carcinom."lS arise in oral leukoplakia. and alypical hyperplasias of endomelrium gi\'C rise 10 endometrial adenocarcinom."lS. Jt is a gOOll lhing lhal skin malignancies do nO! teOO lO ari.se from nevi, because many people have nevi.

BP6 144 PBD6276 15. (A) '11)C Rb gene is the cJassic example of Ihe Iwo-hil mochanism for loss of lumor suppression. Aboul 60% of Ihese lumors are sporadic. Othcrs ¡Ire famili'll, and Ihere is inheritllllce of a mulaled copy 01' Ihe Rb gene. Loss of Ihe second copy in relinoblasls lc:.llls 10 Ihe occuITCnce of retinoblaslomól in childhood. Why palienls who inheríl 11 mutant Rb gene throllgh the germ lioc dcvelop relinoblastoma llnd nOI mosl other lumors is unknown. The Rb gene conlrols the Gl lO S lransilion of Ihe cell cycle; wilh loss of both copies. Ihis importanl checkpoinl in lhe cell cycle is lost.

BP6151-154 PBD6 2B9-290 16. (C) Lymphomas are malignant neoplasms of Iymphoid lissues. lñcy have no benign equivalen!. Monomorphous proliferalions that destroy the nodal architeelUre Sllg~ gesc a neoplasm. A Iymphangioma is composct\ nlOSlly of a proJifenllion of Iymphalics. A m)'eloma is composed of plasma cells and nlOS( oflen involves bone marmw. A leukemia is a ncoplasm lhal arises in the bone lllalTOW anclo spills over itllo peripheral blood.

NEOPLASIA

59

mitotic figure is presenl. 'nlis degree of anaplasia is consistenl with a malignancy. An adenoma is a benign IUmor of glanclular origino Adenocarcinomas ll.nd squamous cell CarcinolrulS show differenliation inlo glandular or squamous lissues. Lciom}·omas are benign mescnchymal IUmors of smooth muscle origino

BP6 135-137 PBD6264-266 18. (B) Cancer grading syslems are l)'pically denoted by I lO IU or 1 lO IV. increasing with won;e differenliation (i.e., more an:.lpla..~ia). A transilional cell carcinoma would be expecled al mis síle. Bladder cancers are not commonly llssocialed wilh parnneoplastic syndromes. Infiltrntion through lhe wall makes Ihe stllge high. This high-gr.¡de, high~slllge cancer ha~ a poor cure raleo

BP6171

PBD6321-322

19. (C) Bccause Pap smear screening can delect clYSp1:1SiólS and in silu carcinomas lh,ll can be lreilled before progression lo invasive lesions, demhs from cervical carcinonm llave slclldily decreased in lhe lasl half of the lwenlieth cenlury. A chesl ratliogmph is an insensitive lechnique for finding early lung callcers. Use of slool guaiac has no! affecla! mtes of t1ealh from coloreetal carcinomas Ihm mudl, bul do noe pul ··fe(:tal deferred" on your physical examination repon, or YOtI will conlribule to lhe problem. Scrum tumor markers have not provetl useful as general screening tcchniques. although Ihey are useful in sclCCloo circumstanccs. Urine cytology is beller than urinalysis for delection of urolheJial malignancies hui does Tl()( hot''C a high sensilivity.

BP6 142 PBD6 272 20. (D) Monodonality is lhe hallmark of a malignancy. In lhe diagnosis of a leukemia, WBC counl is helpful bul not definilive. The DNA conlenl analysis alone cannot define ¡¡ malignancy; Soulhem blol llnalysis for T- or B-cell recc(Xor gene rearrangemenls can define monoclonalilY. Elcelron microscopy is an ¡ldjunct lo diagnosis of lhe type of IUnl(lf. ulctólle dehydrogemlse levc1s are often illcreasetl with Iymphoid prolifemlions bul are nol diagnoslic of Ihe Iypc of prolifcralioll.

BP6171-174 PBD6322-325 21. (B) Developmenl of colonic adenocarcinoma Iypically lakes )'ears. cluring which liffiC a nUnlber of mulations occur within lhe mucosa, induding mUlalions involving such genes as APC (adenomalO\IS polyposis col:i), hMSH2 (human mismalch repair). K-ros, OCC (cleletetl in colon cancer). and p53. 1be accumulalion of mul¡¡tions, rnther lhan their OCCUTTeoce in a specific order. is 1l1OSt importanl for lhe clcvelopment of a carcinoma.. Activóllion of procOOIlcogenes. exlensive regenernlion. faully I)NA repair genes, aoo amplificalion of growth factor receptor genes all conlribule 10 Ihe clcvelopment of malignancies but are not sufficienl by Ihemselves lO produce a carcinoma from a colonic adenoma.

BP6 157, 509 PBD6 '296-297, 832

BP6 135 PBD6 263 17. (E) 'Ibese cells demonslmte l1lólrked ploomorphism and hypcrchromiltism (i.e., amlplasia). /1. bi7..arrc tripolar

22. (G) This is an example of chromosomal tmnslocalion th:lt brings II prolooncogene (c-m)'c) c1o...e lO anolher gene (inllllunoglobulin heavy ch'lin gene). The c-myc gene be-


< not for nle! ." <

60

Port 1

He

.nn_

npo.uiUl>'! ! >

GEN:.RAl PATHOLOGY

comes subjcct lO continOOl.ls stinmlation by the adjaccflI cnhnnccr e1emclll of lhe immunoglobulin gene, Ie.'lding to c·myc O\'ercxpocssion.

BP6 ISO PBD6265 23. (A) p53 is the nlOS! common largct for gcnctic alleralious in human IUmors. Most of lhesc are sporndic mUlalions. although some are inherited. lñc inherilance of one fall[¡y p53 suppressor gene predisposcs to a "second hit'· that knucks OUI Ihe rcmllining p53 gene. HOlllozygous loss of the p53 genes dysreglllates the rcp;\ir of danmgcJ DNA. predisposing individllals lo lllulliple IUl\lors. as in Ihis case.

BP6 153-154 PBD6 290-292 24. (L) Double minutes aoo homogencously slmmng regions sccn on a karyOlype repn:sent gene mnplificalions. Amplificalion of lhe N-myc gene OCClITS in 30% lO 40% of neurobla<;tomas. and this change is associmoo with a poor prognosis.

BP6151

PBD6286

25. (1\'1) Appmxim;ltcly 5% lO 10% of bre<lSt canccrs are familia!, 'lIld 8(YlÁ¡ 01' Ihese result fmm mutalions in (he BRCA-I and BRCA-2 b>enes. The onsct of these familial cuncers is earlier in Jire OHIll Ihe spol'<ldie cancers. The pl'Otcin prooucts of lhese gcnes are involved in DNA re· p;lir.

BP6 153. 156. 630 PBD6 292. 1106 26. (F) 'Ibis pmienl has a family hislory 01' malignan! Il'lelanorna. Familial tumors are oflcn associated Wilh inhcrilance of a defCClive oopy of 0f1C 01' scvernl IUmor suppressor genes. In lhe ca'iC of melanomas. lhe implicated gene is called p/6, or INK4a. 11K' product of lhe p/6 gene is an inhibilor of cyclin-dependcnt kinascs. Wilh loss of control over C)'clin-depcndcnt kinnses. the ccll cyclc cannOl be regulated. and ncoplaslie transformalion is fa"ored.

PBD6920 27. (E) This is ,m in !'illl carcinomn of lhe squmnollS cervical epitheliulll. wilh neopl<lslic growth above Ihe base· ment lllcmbranc. Sueh Cl.\I1CCrs, limited lO Ihe epilbelium. are nonin"asive. ;¡nd IOC,ll excision h;¡s a virtual 100% cure mle. In situ Icsions do nol gi"c rise lo I1lCl'L<;tases. Lcsions limited to Ihe epilhelium are low grade. Bccause 01' its origin in lhe epilhelium. Ibis ncoplasm is not dcrived fmm fibroblólSts.

BP6 136-138 PBP6265-266 28. (8) The elnbor.llion 01' a \'ariety of enzymes by IUmor cells aids in degradnlion 01' eXlrllcellular malrix ;llx! invasivencss. C:lthepsin 1) is a cysleine prolcin.1se IhOl! cleaves a varieey of substrnlcs such as libroncctin and [aminin. High Icvcls or lhis cnzymc in UlIllOr cclls are a.ssocillled wilh grcater invasi\'eness. Angiogencsis is mcdillled I\1n;nly by rnlsic libroblast growth factor nnd v",scular enJ~ lhelial ccll growlh fnctN. I)iffcrcnlimion. aneuploidy, and helerogeneilY an.· regula!ed by pmtooneogencs and lumor supprcssor genes.

BP6 162 PBD6303-304

29. (e) R;x!intion is oneogenic. Cancers 01' lhyroid <lOO bune oflen dcvclop foUowing radiation exposure. Leukemias can occur as well. Hcpmocellular carcinomas can arisc in cinhosis from chronic alcoholism. AtaXia tclangiectasia is an inheriled syndrome lbal cames an incrca..oo risk for dcvelopmenl 01' lcukcmias aOO Iymphomas. Trnum:¡ is nol a risk 1'01' cilncer. bul e\'eryonc rcmcmbers lrnum,llie cpisodes and makes nn associalion wílh them aOO subscquen! henllh problcms. Arscnic exposure is llncommon. and it 1c;:l(!s lo Iung óllKI skin canccrs.

BP6 165 PBD6310 30. (E) HPV Iypc.<; 1l1. 18. and 31 encode protcins Ihm bind pRb wilh high amnílY. rcsulting in loss 01' (lunor SllpprCSsor naivity. Scventy-five lo ne,lrly I(X)% of sqUi.lmous cpithelial dyspl:L<;ias and Cllrcinomas of Ihe cervix are associmcd with IIPV infCClion. EBV is as.<;ociatcJ wilh sorne malignanl I),mphomas aOO nasopharynge.'1I carcinomas. HBV is a"SOCimcd wilh hepl.\locellular carcinom.1S arising in the seuing 01' regencrnlion in chronic li\'cr injury. HIV dre.<; not affeet pRb. bul lhe loss 01' immune regulalion pmmotcs devdopmcnt of Iymphoma<; and Kaposi sarcom;¡. CYlomegalovims docs not pólrticip.1te dircaly in carcinogcncsis.

BP6167 PBD6311 31. (E) Alplm-feloprolein (AH») is II tumor markel' for hepatocellular carcinomas and SOITlC tcsticular carcinomas. The scrum proslale-spccific anligell is a helpful marker for proslalc adenocarcinoma. Squamous ccll Cl.\rcillOma<; uf any sitc do nol h.1ve g()()(] spccific lumor markers. A scrum inununoglobulin Icvcl wilh prolein c1cctrophorcsis helps to dingnosis m)'c1orna. Gastrointeslinal lr.K:1 adenocarcinom:lS n1.1Y be accomp.1nicd by c1evmions in lhe scrum carcinocmbryonic anligen.

BP6173-174 PBD6 325 32. (e) He has Cushing syndromc from cclopíc conieolmpin produclion by Ihe tumor. a form 01' paronooplólslic sYlldrorne COmll1(JIl lO sml\1I ccll carcinomas 01' Ihe lung. Hypcrcalcemia from a IYrH~rclaled protein is more I)'pically associatcd with pulrnonmy squmnous ccll carcinOI1l;L<;. Erylhropoielin production with po[ycylhemia is more likcly lo be a.ssocialed with a renal ccll cilrcinonu Insulin mx! g;L<;lrin produetion are musl often seell wilh islel ccll tumors of the pancrca...

BP6171

PBD632O-321

33. (A) A discrele sl1lólll m.1SS sueh as this is probably benigno Adenolll.1S arisc from cpithelial surfaces. A llamarIom:\ is rare and is a benign mass composetl of lissues usually found al the site of origino A S<1.rcoma is a m;lliglIanl nooplólsm arising in mescnchymal tissues. A chorisloma is a bcnign mass composed of lisSl1es nol found al lhe silC uf origino A nevus arises in Ihe skin.

BP6133-134 PBD6261-262 34. (B) Overexprcssion 01' Ihe /)(:/-2 gene prevents apoptosis. allowing accumulillion of cclls in Iymphoid lissllCS. Incrcased 1}'Tosine kina...e aclivilY results from mulations


< not tor sal .. 1 :> < t<<l ¡;¡IlA 1l¡lOll,lUO< I :>

Chapter 7

NEOPlASIA

61

affeeling Ihe (Ibl (lncogene. Gene amplifiC<ltions are Iypically seen to affeel (he c-e,b 82 and m)'c oncogenes. Re· duced DNA repair occurs in Ihe inheriled disorder xeroderma pigmenlosa_ Loss of cell cycle inhibition results from loss of lumor suppressor genes sllch as p53.

41. (e) Carcinomas like lo melaslasize through lymprullics mosl oflcn, usually lO regional ll(J(les firsl. However. hem¡ltogenous melaslascs are nlways possible. Aboul one half of ;lll cerebral melaslascs come from lung. Soft tissue melaslascs are rareo .18 are splenic melaslases.

BP6 154-155 PBD6 294-295

BP6 140, 162 PBD6 269-270,305

35. (C) 1ñc ras oncogcnc is lhe mosl common oncogene involved in de\'elopmenl of human cancers. Mulalions of lhe ras oncogene reduce GTPase 3Clivity. and ras is Irnpped in an aclivaled GTP-büt.md slale. 11 Ihen signals the nueleus through cyloplasmic kinases. TIle 111)'(' oncogcnc is él InlnSCriplion<ll aetivalor Ihal is overexpressed in many lumors. Mutalions of lhe abl oncogene c..,use gre<llly increased Iyrosine kinase aetivily. bul Ihis is nOl relaled lo lhe hydrolysis of GTP. TIle IIeu oncogene encodes growlh factor receptors lhal are amplified in certain rumors. T1le sis oncogene enrodes plalelel-deri\'ed growlh faclor receptor-13. which is o\'erexpressed in certain astrocYlomas.

BP6147-148 PBD6279-2Bl 36. (H) The smaJI, discrele nature of this mass and the faet thal it has changetl liule suggesls a benign nooplasm. 1l1e red color suggesls vascularily. A hem..,ngioma is a common benign lC1iion of tile skin.

BP6 135 BPD6 263

42.

(D) "I1lis is lhe appe.,nmce of metastalic lesions from

a malignant neoplllsm, wilh mulliple lumor masses present. Dysplaslic lesioos do nOC produce large masses. Allhough sorne benign lumors such as leiornyomas of the ulerus can be multiplc. (his is nol lhe rule in liver. and hep<1lic adenomas are rare. Though hepaloccllulnr carcinomas can llave "salellilc" nodules., widespread nodules sueh as those secn here are more chamcleriSlic of melaslases. Resection of mulliple melaslascs is usually fruil1ess.

BP6 139-140 PBD6266 43. (el lOe rapid fro7.en seclion of reseetion margins helps delermine whether enough colon has been resectec.l. Fine-needle aspirnlion is used for prooperali\'e diagnosis. Serum IUmor markers ma)' aid in preoperati\'e diagnosis 01" poslopcr<.ltive follow-llp or neoplasms. Electron microscopy takes al lc.\S1 a d<lY lO perfonn and helps delennine lhe cel1 Iype. Row cylomelry can be done in several hours bul is useful mainly ror progooslic infonnation aOO is no! a "SIal" procedure.

BP6171-173 PBD6322-325 37. (e) No!ice lhal the disordcrly, atypical epllhelial cells involve lhe entire Ihickness of lhe epithelium bul thal lhe underlying basemenl membrnne is inlact. wilh no invasion. Carcinoma in sil\! is confined lo lhe epilhclium; if lhe basemcnl membr:me is breached, lhe lesion is no longer in situ bUI mther invasive.

BP6 137 PBD6 267 38. (U) A lerntorna is a Ileoplasm derival I"rom IOlipolenlial germ cells Ihm differenli:lle into lissues lh:lt represent all three germ layers-ccloc.!erm, end<xlerm, and mesoderm. When Ihe e1emcnls are all well differelllialec.l. Ihe lleop1:lsl11 is "nUllure" (i.e., bcnign).

BP6 135 PBD6 263 - 264 39. (O) CD8+ T cclls recognize peptides presemcd by MHC c1ass I alltigens. In many IUl11ors. especially melanÜ'" mas. Ihe Iumor cells produce peplidcs th¡ll can be presenled by MHC c1ass I molccules. If such peptides are nol produced by other cells. lhe CD8+ T cells specific for sllch pcptiúes Iyse mel¡lIloma cells bUl not nonnal melanocytes or other normal cells.

BP6166 PBD6315-317

44. (E) Although neoplasms begill their careers as munoc10nal proliferations, addilional mUlations occur over time. leadiog lo subclones of neoplastic cells wilh VariOllS prop-mies. This may "lIow mel<lsló.lses, grealer invasivencss. resjslance lO chclllothemp)', anc.! rnorphologic differen<:es lO occur over time. Because sarcomas are ntre in Ihc lung. the lung ffia<¡S is slatislically <l melastasis. Inheritance of a mutanl Rb gene is mosl likely lo le"d to childhood retinoblaslCHnas. Pulmonary sarcomas are nol rclalec.l lo smoking. Loss of tumor suppressor gcnes, nol oncogenes, is relmed lo lumor developmenl.

BP6 160 PBD6 320 45. (O) Squamolls cell carcinomas of Ihe serola1 skin in chirnney sweeps WllS Ihe tirsl c.!ocumelllalion of an OCCll{XlIional risk for C¡lllcer. Endcmie Kaposi sarcoma is rare, and epidemic K<l[Xlsi sarcoma was nol secn wilh any frequency until AIDS bccanle widespread in Ihe lale twenlielh cenlury. Bre.\S1 cancers are rare in meno The gre.ll increllse in lung cancer was 1101 seen until lhe rise in [XlpularilY 01" cigaretle smoking in Ihe twenlielh centur)'. Maoy adenocareinomas of lung are no! relnted 10 smoking. Osleosarcomas Ill:lY occur al siles of bone subjccled to prcvious irmdialion.

40. (B) Such a large, inegular, ulcemled mass is mosl likely malignan!. aOO lhe epilhelium of lhe bladdcr gives rise lO carcinomas. A p<'pil1om'l is a benigno localizcd mass lhal has an eltophytic growlh pattem. An adenoma is a benign epilhelial neoplasm or glantlular lissues. A sarcoma is derived from cells of mesench)'mal origin; sarcomas are moch less common lhan carcinomas. A fibroma is a benign mesenchymal neoplasl11.

46. (O) P'<.Iltems wilh heret.lilary nonpolyposis colon carcinoma (HNPCC) inheril one defeetive copy of mismatch repair genes. An)' of several human mism:llch repair genes are involved in lhe deve10pmenl of HNPCC. Mulalions in mismalch repair genes can be deleeted by the presence of rnicrosatellite inslability.

BP6133-134 PBD6261-262

BP6508 PBD6 295-296.B31-633

BP6 163 PBD6 306


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62 •

Port I

GENERAL PATHOlQGV

47. (O) The myc oncogenc is comlllonly aClivated in Burkill Iymphoma bccause of a 1(8;14) lmnslocmion. 'The m)"c gene binds DNA lo c.'lUSC Imllscrip:ional aclivmioll of !,!rowlh-relalctl genes such as Ihm for cyclin DI, re.sultillg in aClivalioll of Ihe ceH c)'cle.. p53 and APC are IUmor suppressor genes thal are inaclivaloo in many cancers. inc1uding colon callcer (APe). ras oncogcne cocodes a GTPbinding protein Ihal is localoo under lhe cell membr.me.. c~erb 82 (also known a." HER2) cncOOes gro\\th faclor receplor localcd on lhe cel! surface.

BP6 149 PBD6 2B2 48. (O) 1ñere is an increased risk for coloreclal carcinom;l wilh ulccmlive colilis. Dcnign neoplasms. cvcn if lTlultiple, do not lcnd lo bccomc malignan!. Asthma is a sporatlic condilion Wilhol1l a signiticnnl risk for canceL Dcgcnermivc ehangcs wilh aging are not a risk for caneer. lllthough lhe risk for cancel' increases with :lging beCllUSC of olher f:lclors.

BP6144-145 PBD6276 49. (A) Epilhclial dysplasias. cspecially Ihose thm are sevcrc. can be lhe prceursors of carcinomas. and lhis is a key rcason for Pap smear screening. 11lc incidence of cervical carcinoma tlccrc..'lSCS when rouline P:lp smears are pcr. formcd. Temlomas show well-differentialed elemcnls derivcd from all lhe genn cell lól)'ers. and lhey do nol manifesl as epilhelial dysplasias. Severe dysplasins are nol amcnable lo anlibiOlic lhempy. Ccrvical dysplas..ias are llOI heredilary.

BP6 137 PBD6 266 50. (C) A 1ll..11ignanl ncoplasm has :l lcJklency lO invadc locally. 1\ benign ncoplasm is oflen well circumscribetl. allhough ól lnlC célpsule is l111COmmon. and compressed nor111.11 sl1rrounding lissl1c appcars lo forro a discrcle bonIer. Such a solitary mucosal lesion is unlikely lo represent a mclast:lsis, and lhc locali7..oo Icsion is ensily rcscclW. Without a family history, a familial cancer wilh high recurrcnec risk from lllulliplc polyps is unlikcly. and local cxcision is adequale. Bec:msc lhe lesion is dcfinilcly malignam, il lIlusl be remo"ed before il incrcascs in si'l.c and inv<ldes 10cally or sprcl.lds clsewhcrc.

BP613B-139 PBD6 267-268 51. (8) The condilioo iJl this famit)' is xcrodcrJrul pigmentosum. an autosomóll reccssive disonJcr. Minor dmnage from sun exposure is nOl rcp'liroo. rcsuhing in mUl<ltions 1h.11 1c:.w.1 lO developmcnl of skin cnncers. ProtOOllcogenes lhal regulme lmnscriplion or eneocJe groWlh faclors or lheir rcccplors are associalw wiltl othcr canCCl'S. as are genes t11.11 rcgulmc the ceH c)'c1e..

lalion of codomclrial growth (i.c.. hypcrplasia). which has a prornoling effcel when mul'llions occur lo produce carcinoma. Tumor hderogencity does 001 refer lo IWO separ.lle kiods of ncoplasms; il refers to helerogencity wilh a gi\'en lumor or melaslasis.. A paraneoplaslic syndrome miults (mm cclopic secretion of a hormonc by lumor (e.g.. lung cancer cel1s producing cmiCOlropin). Inhcriletl suscep:ibilily can ncver be complelely cxclu<.led when a pcrson has 1\\"0 lumors. This. fOl'" eumple. c.'Ul occur in paLients wilb inhcrilcd nll1tations in Ihe p53 gene. Howe"er, in Ihis case. Ihcrc is a clear hortnOflal b.'1Sis for !he second IlImor. Fnulty lumor supprcssor gcnes are not involvcd in hormonal prornolion of a neoplnslll.

BP6 164-165 PBD6308 54. (A) nlC MI designalion indic111es lilal dislanl metllS· tases are prcsent. Elcvl1loo corticolropin lcvels indiC:lle se· crclioll (lf an CClopic hormone lhal n1:ly produce a paraneoplaslic syndrome. A TI designation me:lIls thm Ihe ovcrall Si7.e uf lhe tumor is not 1argc. TIle TNM syslcm is lIsetl for slaging. nol grading.

BP6 171

PBD6321-322

55. (B) Primary or secondary immunodelicicncy discases carry an increasetl risk for neoplasia. particularly l)'mpl'lOItlólS. 8-ec11 1)'lllphomas of lhe brain are HXX>-fold more common in par.icnls wilh AIDS Ilmn in lhe geneml populalion. Diabeles mcllilus can h:lve a varielY of compliCóllions. allhough nOl neoplasia. Hypertensioo can lcad lO CNS hemorrhages. Multiple sclerosis is a dcm)'e1illólling disea.'iC wilhOllI a significant risk for neoplasia. Tuberculosis lIS a chronic ¡nfcelion may !cad lO amyloidosis. not neoplasi:l.

BP6169 PBD6 315 56. (O) Thc high alkaline phosphatase conccnlratioll in a p;.llicnl wilh proslatc cancer suggesls thcre are melaslascs lo bonc. Proslale C<1nccr is no! kllOwn for paraneoplaslic effecls. Tumor extensi(.'n lo sofl tissue.<; aOO mnjor organs does no! produce an eJevatcd alkaline phosphmasc levc!. excCpl in the liver. Th,~ gradc of thc tumor is nol a major fnclor in lhis process, ahhough higher-gradc lesions arc more likeJy lO be melastalic. Angiogcncsis does nol affccl alkalinc phosplmlasc.

BP6171-172 PBD6320-321 57. (C) Lung cmlceri incrcllsed cnorrnousl)' in lhc Iwenlielh cemury bec..'luse cig'lrelle smoking bcc.'lnlC so popular. As the numbcr of rersons who smokc in a populalion incre:lSCS, so do lhe I.umber of lung Cólncers. Sorne CólllCers of lhe urin&)' lmcl. oral cnvity. esophaglls, and pancre:lS are :lIso causally relncd to smoking.

BP6145 PBD6 275-277

BP6 142 PBD6 2; 2

52.

58. (F) The decrcase in lile nllmbcr of gastric canccrs may be rclaled lo nxIueet1 numbers of dielary carcinogcns. but lhe exacl rcason is ob.<>curc.

(e) Hc has HNPCC. which is dislinguished from lhe

Chl\.~ic

familial polyposis wi(h hundrcds of polyps lhm :lppcólr in childhood. HNPCC arises from inheritance of faulty DN/\ mismmch repair gcnes.

BP6142 PBD6272

BP6 156-157 PBD6295-296 53. (A) Eslrogen. like nmny otilO' honnones :uld drugs. is nol by ilsclf carcinogcnic. bul il is responsiblc for slimu-

59. (8) Worldwide. incre:lsing numbers of skin cancers OCCllr bcc:IUse of sun exposllre. TI1C ullnlViolet light dam:Iges Ihe skin and dam¡¡ges cellular DN A. [cólding lO mlllll-


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COOpte!' 7

tions Ihal escape cellular repair mechanisms. Smoking is relatetl lO many cancers. bul skin caocers are llOI lypically incl!,kletl with Ihis risk factor. Chemothernpeulic agents have carcinogenic potenlial. partieularly the alkylating agents such as c)'clophosphamide. bul leukemias and l)'m-

4-poH'I'.

w

>

NEOPlASIA

โ€ข

63

phomas are lhe usual resulto Asbeslos exposure increases lung carcinoma risk in smokers and can lead lO lhe rafe meSOlheliomas of pleura. Allergic reaclions do not proRlOte canee<.

BP6 165 PBD6 310


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CHAPTER

8 Infectious Diseases BP6 Chapter 9 - General Pathology of Infectious Diseases PBD6 Chapter 9 - Infectious Diseases

l. /\ 35-year-old renal Imnsplanl reclplcnl W<lS being Irc:lled Wilh cyclosporinc, <l7..athioprine. and high doses {lf corlicoslcroids. Whilc on lhis Ire:llmenl, Ihe palienl bcgml lo experictlce hcnd<IChes aoo beC<lme lethargic. A clínic:}1 diagnosis of meningoenccphalilis W:l'i lI\adc. He dicd 7 d:lYs laler. AUlopsy rcve:lled a gclalinous meníngeal exudale, and 00 sccliooing of lhe brain. Olultiple small cysllike arcas were sccn IhroughoUI lhe brain. Under Ihe microscope. dIeSe arcas conlaincd roundcd slructures with a prominelll C<lpsule 111..·11 staincd brighlly w;lh mucicarnline (i.e., hislologic slain foc mucin). Which of lhe following lests would h<lve becn fIlOSl uscful rOl' diagnosis or lhis conditioo during life?

O (A) Examilli.\lion or cerebrospin:ll fluid (CSf) wilh an O (B)

O (C) O (1)) O (E)

India ink prcpamlion Dclcrminali{ln of Ihe CSF glucosc and prolcin conlem A bruin biopsy slaincd for viml inc!l1sions Cullurc of Ihe CSF fOf SlrepuJCoccus pnellllum;lIe A polymemse chain reaetion (PCR) asS:lY lO octcct Epslein-Burr virus (EBV) genomc in lhe lyOlphocyles isolatcd from C5F

2. Ouring a lrip lo Cenlml Amcric.. after hurricane MilCh, a 22-year-old fem..le de\"c1op> a low-volume, bloody diarrhea. This dianhea rcsol\'cs in a couple of weeks. Al horne 8 wecks afta Ihe diarrhea is gonc. she begins lo llave some dllll right uppcr quadrnnl pain. An abdominal cr scan reveals an irregular. 100m mass in lhe right liver lobe lhal h:ls cenlml necrosis. Which of the following infc<:lious agenls is pmb:lbly implicatcd in lhese evcnls? O (A) O (O) O (C) O (1) O (E)

64

Gianlill lamb/ill Sa/IIIQnella 'Y1Jhi EllIwlIcelx, hislOfyliclI Campylolx,clu jejuIli Yersinia enlerocoJit;ctI

3. A male p:llienl comes inlo a physician's offK:e complaining of a nonleooer ulccr on lhe penis 111..11 has becn prcsenl foc a week. A scraping of lhe Icsion is pcrformcd and a darkficld cxamin.alioo is posilive for spirochclcs consiSlenl with Trepo1li!ll1ll lXlllidfllll. A biopsy of Ihe lc.o:ion is masl likely lo re\'eal O (A) Grnnlllomas with slIppumlion O (B) GI1Ullllomas with ct\SCl.llion O (C) Acute inf1mnmation wilh abscess fonnation

O (O) üblilcralive endarterilis wilh pcri\'nscular Iymphocyles and plasma cclls O (E) GlImmmous inflamOlation

4. A 24-year-old m..le tl..lS a fever wilh mainly upper rcspirnlory lrnct symptoms-runny nosc. sneezing. coughing. Tbese sYlllploms last for a few days. and lhen he is bel1er, wilh no scquclae. His ;nfCl1ion is promotcd by lhe binding of which of the following organisms lO intercellular adhesion molecule-I OCAM-I)? O (A) Mycoplasmll pllew'IOfliae O (B) HaemopIJiflt,· illJfflenzlIe

O

(C) Rhinovirus

O (D) Epslcin-Oarr virus O (E) Neisseri(l meninRi/idis

For each of lhe (»lIienl histories in qucslions 5 Ihrough 7. match Ihe mosl dosely associatcd infeclious orgllnism lh<ll can cause lhe clinic;'ll findings: (A) (O) (C) (D) (E) (F)

Allcyfosloma duode'llIle Aspergil/us fWlliRlI1US Borrelia recurremis Brogia mlllay; CryplococcllS lIeofonlUIIIS

C)'lomeg:llovirus (CMV)

(a) Leislmllmill (10"0\,(111;

(H) LiSle,.ia mOI1OCJ'ogene.~ (I) MycoIJlIcferillfll lepmi' (J) O"cJlOcerC(I VOlVllhl~· (K) P/asRllXlilllllflllciparum

(L) Poliovims (M) Tae";ll solilun (N) TOxoplllsma gOflllii (O) TryptlllOsol/U/ gambietlSt>


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5. A prcvioosly hcalthy, 21-ycar.-old malc prcsents with 11 ncw-onset sci7..ure disonlcr. A he,ad compuletl tomogmphy sean rcveals multiple 0.5- lo 1.5-em, cYSlic, perivenIricuJar and meningcal lesions. ( )

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6. A 9-)'car.-old girI has a mild febrile ilIncss with a pharyngilis. She is belter in a wttk. Over thc ncxt 2 months. shc has irtCJ"Cm.ing right-sidcd facial drooping with inabililY lo clase her righl ere. ( )

7. An AmeriC<ln soldier slationcd in Saudi Ambia has dcveloped llbdominal enlargemcnt ovcr thc p'lSl 7 wceks, accomp"'Ulicd by 11 IQ-kg weighl loss alx.! hyperpigmclltation of skin. Physical examination revcllls hcP."losplenomegaly llnd lymphlldellop.'IIhy. With progression of lhe discasc, he dcvclops pancYlopenia and succumbs lo S,reptOCOCCIIS IJlleumonio.e scpliu:mia. ( ) 8. A woman comes to Ihe health celller beCllUse shc has a smHII vcsicle on he.. righl labium mlljus. She is sexually aClive. Inguinal Iymph Iludes are palp<lblc. OCC¡,USC she has ¡, prior hislory of Iymphoma diagnosro lO years earlier, 11 biopsy of onc of lhe Iymph rlOt.lcs is donc lo excludc maliglllmcy. Hislologically. the biopsy shows muiliple absccsses in which centrnl necrosis is surrounded by palis..1ding hisliocYles_ nris morphology, combincd with the cliniC<ll piClure. is most represenlalivc of which of Ihe following corx.lilions?

O O

INFEcnOU5 DlSEASES

65

(e) Rcspir.Jlory sync)'lial virus (1) Herpes ZQSler virus

O (E) Adenovirus 10. A 6O-ycar.-old male presenlS wilh blocx.ly diarrhea, abdominal Clamps, and fever. He is .x.!mitled lo (he hospital for workup_ Sigmoidoscopic cxaminatlon reveals ulceralion in the cecum aOO ascending colon. Microscopic examill<llion of a colonic biopsy sho\\'s flask-shaped mUCOS<lI ulcers wilh eXlensive necrosis aOO a moclest. IlOnspccific infl:lmnlóllory response. The ulcers do not penelrale lhe muscularis propria. The nlOS! likcly agent responsible for Ihis p',licm's dianhea alK.l mucosal ulccmtion is O (A) O (O) O (C) O (D) O (E)

Gio.rdia lo.mbliu Emumoebo. IJútolytica Shigellll spp. SlIlmOllel/lI spp. Vibrio cIJoleme

O (A) Chlamydial infection (i.e., Iymphogranuloma venercum)

O (O) Herpes simplex virus infectioo O (e) Recurrent non-Hudgkin Iympllom:.l O (1) Candidal vaginilis O (E) Oacterial vaginosis 11. A 24-year-old female has had ¡, bloocly diarrhea for lhe pust few days. Colonosoopy reveals Ihe appeardnce of lhe reclum arx.! descending colon shown here. She is lremed wüh antibiotics bul develops a ehronic arthritis afler thc diarrhe¡l has resolv<xl. HLA Iyping is done, and she is found lO be HLA-B27 posilive. Which 01' the following organisms W¡1S mosl likely lO !lave been identi¡ied in her diarrhe¡, slool'! O (A) O (O) O (e) O (D) O (E)

9. A human immunodcficiency virus (HIV)-posili\'e male has ¡l p1llSma liler of 26,800 copies of HIV-I RNNrnL. He prescnls wilh incrcasing rcspiralory difficulty, alK.l a tr.Insbronchial biopsy is perfonncd. On the basis of lhe clinical and hislologic filx.!ings shown in lhe figure. lhe moSI c....USlIlive organism is f. O (A) Epslein-Oarr virus (EOV) O (B) Cytomegalovirus (CMV)

Vib,.¡o c!lQlero.e SJ¡igel/o. ftexlleli EntlJ.ll~bo. hislolyticu

Salmollella typJ¡i Helicobo.cler pylori

12. A 23-year-old female is admiued lo the hospital with a 2~ay history of inc:rcasing delirium. On physical examination, she has an acule pIlaryngilis w:ith an overlying diny whilC, lough membrane. She has paresthesias with decreased vibmlory sensation. A Gram slain of lhe pharyngeal membrane reveals numerous small gram-posilive rocls in a fibrinopurulenl exudate. She has an irregular cardiac rhylhm. A chesl rddiogmph reveuls cardiomegal)'. Whal is the mechanism for developmenl (lf her canliac dise:.lse? O (A) Microabscess form:ltion O (B) Endoloxin~medillled hypotension and shock O (C) Vllsculitis wilh thrombosis and inrarction


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GENERAL PATHOlC:X;Y

GranulomalOus inflammation

improves aftcr a coursc of !herapy wilh gcntamicin. Which of (he fDtlowing complicalioos of thh. infcetion is lnosl likely to devclop?

O (E) ElaOOralioo of an eXOl.oxin 13. A 15·year-old malc has a smal! csc:har fonning around lhe site of rcmoval of a tick from his Icft foreann. A hcmonhagic rash devclops OvCT the ocxl fcw days in\'Olving his trunk. exlrcmilies. and C\'cn his pairos alld soles. 11len. small 0.2- to O.4-cm foci of skin necrosis devclop 00 his fingcrs and loes. Which of lhe following orgallisms is mosl likcly rcsponsiblc for thc dcvclopmel1l of thl.'Sc findings? O (A) Rickefl~'ia rickefl.~·ii O (8) MycolJtlcJerill1/l lepme O (C) Yersinia pestis O (O) Borre/ia blfrgdor/eri O (E) LeishmmJia brazj/iensis

O (A) Gas gangrcne O (8) Cavilar)' granulomas

O (C) Absccss formatioll O (O) Bulloos empnyscma O (E) Adenocarcinoma 17. A bronchopncurnonia in a 68-)'ear-old female is complicatcd by abscess formalion and bronchoplcural fistula surroundcd by a pronounced fibroblastic rcaetion. Al llUlopsy. wilhill lhc arca of absccss formation are small. grossly visible. 1- to 2-mm. ycllowish "sulfur granules." Thc organism mosl Iikcly to produce this appcarance is O (A) AdifUJIIIYl:es i.\·raeli O (B) Blaslom.,·ces de",uuitidü O (C) Ch/amydw pnellmoniae O (O) Klebsiello pnellmOlliae O (E) Mycobacteriwn kansafii

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14. 'Illc patiellt shown here ha.. had a high fever for the pasl 3 days. Which of the following organisms is mosl likcly lo produce Ihis finding? O (A) C/ostr¡dium boJufinllm O (B) Efc1lericllia coli O (C) Neisseria gOllOI"r1lOeae O (O) Staplly/ococms e,Ji(lennidis O (E) StreplococclIS pyogenes

15. After World War 1. many persons dicd fmm an influenza pandemic lasting several years. Which of the following changes in Ihe "iros is rcsponsiblc for such pandemics of influenza?

O (A) MutaliOlls of the hcmagglutinins and

neuraminida~

O (B) Increa..ed abililY lo bind to ICAM-I receptor

O (C) AbililY lo c1aborale cxOloxins

O

(O) R(.'Cornbinalion wi!h RNA segmenls from pig vi-

ruses O (E) Acquisitioll of antibiotic rcsislance genes

16. A 52-year-old male has a rever wilh neulrophilia. and he has a cough Ihal worsells over scvcral days. Klebsiel1a 1JtU!lunonwe is culturcd from his spulum. "lis condilioll

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18. An II-ycar-old boy had episo<lic fcvers for a w(.'Ck alld Ihen devclopcd a scvcrc headaehe. He bccamc progrcssivcly somnolclll alld dicd a wcck later. Al autopsy. Iherc is markcd ccrcbr.ll edema with areas of cerebral softcning. The microscopic llppcarance of a cerebral vein is shown in lhe ligurc. In which or the following organs does Ihe infeclious agcnt pnx1ucing his disca~ proliferalc mosl? O (A) Heart O (B) Liver O (C) Brain O (O) Lympn nodes O (E) $plccn

19. A 29-year-old malc has had hemaluria for !he p;.lsl month. An abdominal mdiograph rcveals a small bladder outlincd by a rim of calcification. Cystoscopy is pcl1'onn(.'d. and Ihe entire bladder mucosa is crythematous and granular. Biopsies are lélken. Which of lhe following histologic findings is mosl likcly to be scen? O (A) Eggs or ScltisJo$omo llematobilUn O (B) Larvac of Tricllinelia spiralis


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(C) Taenia so/ium cySlS

O (D) Acid-fasl baciUi O (E) Migrating Ascwú' IlImbricoide;

20. A 24-year-old maJe college sludent seen by Ihe Health Service complained of 3 weeh 01' cough, fever, and shortness 01' brealh when walking. The physician found normal cardiac examinalion resulls, and a chest radiograph demonSlralt::d mild haziness in the lungs. A presumptive c1inicai diagnosis of M)'coplasma pnellmoniae was made after he wa'> found to have an elcvalt::d cold agglulinin tiler, and he resfXlnded lo erylhromycin therapy. Whit:;h sel 01' Ihe following hislologic changes is mosl likely responsible for the pulmonar)' symploms in this condition?

O

(A) Neulrophils wilhin bronchioles. eXlending inlo alve-

oli O (B) Granulomas with Langhans gialll cells O (C) Pulmonary infarels with vascular occlusion by mi-

croorganisms

O (D) Monolluclcar (Iymphocytcs, hisliocytes) interstilial infillrale O (E) Colleclion 01' neutrophils and fibrin in Ihe plcural space (empyema) For each 01' the c1inical hiSlories in queslions 21 and 22, malch Ihe most c10sely associaled leltered host for a parasilic infeclion: (A) Cat (8) Cow (C) Flea (D) Louse (E) Mosquito (F) Pig (G) Ral (H) Sand ny (1) Snail (1) Tick (K) Trialomid bug (l) Tsetse fly 21. An 18-year-old female gives birth al 33 wLocks' gestation 10 a sliUborn boy. Autopsy revcals exlcnsive perivenlricular cerebral necrosis with calcification and vascular lhrombosis in the circlc 01' WiUis. Smal] arca'> ol' necrosis also appcar in heart and lung. ( ) 22. A 6-year-old Mexican girl develops l'ever wilh neutropcnia, followed by disseminated illlravascular coagulation over the course 01' a week. She dies ol' an intracerebral hemonhage. ( ) 23. While repairing a fence al his farm. a 40-year-old male culs lhe skin over his shin. This wound heals withoul any complicalions. Se,'eral days later he begins to develop muscle spasms 01' his I'acc and exlrcmilies. These spasms worsen lO Ihe poinl of severe contr.lclions. Which of Ihe following aClions by a loxin is reslxmsiblc for Ihe c1inical fealures in Ihis case'!

O (A) Degradation 01' muscle cell membranes by phospholipase C

INFECTlOUS DISEASES

67

O (B) Illhibilion 01' acelylcholinc rdease at neuromuscular

junclions

O (C) Slimulalion 01' adenylale cydase produclion O (D) Cleavagc 01' synaplobrcvin in Ihe synaplic vcsicles 01' neurons O (E) Cylokine rdease by T Iymphocyles

24. Al a convenlion 01' velenlllS, seveml 01' the participalllS begin lo develop respiralory difficully and fever. Thesc men are bclwcen 58 and 73 ycars old, Ihey are all smokers. and many have chronic obSlruclive lung disease. Chesl radiographs 01' these men demonstmle cxlensive infiltmtes alld small abscesscs. Sputum specimens reveal as many macrophagcs as ncutrophils on rhe cylologic smears. Which 01' the following organisms is most Iikcly to be identified in Ihe sputum'!

O (A) CylomegaJovirus O (B) Pnellmocystis carinii

O (C) Le¡¡ümelfa fJllellmophila O (D) Bllrkll()/(/eria cepacia O (E) Lisleria monocytogenes

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25. A 25-year-old male is involved in a vehicular accident in which he is ejccled from Ihe vehicle. He suslains a compound fracture of his right humerus. Several days laler, he ha'> markcd swelling 01' his righl arm wilh crepilance. A Gnlm Slain 01' exudale from the wound sile has the appearance as shown here. Which 01' Ihe following organisms is Ihe causati,·e agenl for his infcclion? O (A) Canllida albicans O (B) Listeria nwnoc)'togenes O (C) HaemOf)/¡jlus inflllenz.ae O (D) C10stridimll perfringens O (E) Bactemides fra8ili~·

26. For seveml weeks. a 52-year~0Id malc has had a chronic cough with low-grade fevcrs. A chest radiograph shows scaltered. upper lobe. 0.3- lo 2-cm nodules and hilar adenopathy. A finc-ncedle a,>pirale of one 01' Ihe nodules shows inflammalion wilh monollucJear cells, inc1uding macrophages thal, wilh pcriodic acid-$chiff (PAS) slain. show inlracellular, 2- lO 5-f.tm. rounded. yeasllike orga-


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68

GENERAL PATHOLOGY

Part'

nisms. Which of the following infl:clious diseases is he most likdy lo have?

O O O O O

(A) (B) (C) (O) (E)

Coccidioidomycosis Candidiasis Cryplococcosis Hisloplasmosis Blaslomycosis

28. A 22-year-old mate dcvelopcd a l-cm, mbbery, red challcre on his right forearm. Afier several months. he devdopcd splcnomcgaly and Iymphadenopalhy; and 2 months lalcr he succumbed to progressive wasling with cachexia and dccreased melllation. Al Ihe lime of his death. his pcripheral blood smear had the appcarance depiclcd in Ihe figure al Ihe botlom of the left column. Wherc is Ihis discase mOSI likely lo have been acquired?

O (A) WCSI Africa O (B) CenLral America O (C) SOUlheast Asia

O

(1)

Soulhern Europc

O (E) PolyncsilJ

Councsy of Dr. Willy Presscns. HarvanJ S<;hool of 1'1Iblic Hcalth.

27. The wndition shown here in a 40-year-old malc has been progrcssivdy worsening for years. He also has inguinal Iymphadenopathy and scrotal edema. Which of Ihe following infcctions is Lhis palicllt most likcly lo have? O O O O O

(A) (B) (C) (D) (E)

Schi~üM'ol/lll n/ansoni EchinococclIs 8J"(l/Iulosis Trichinella spimlis LeisllJMnia lropiClI Wllchereria hcmcrofti

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O (A) O (B) O (C) O (O) O (E)

E~'cherich¡ll ('oli

Hepatitis B virus Plmmo(/illJll vil'l/x

Cun(lilla albicans PnellJJwcyslis carinjj


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A lrading ship from rhe Black Sea docks al an lIalian port. The ship's crew ha<; bcen decimated from an illness martcd by a shOl1 limc course of days from onset of inguinal Iymph nooc enlargemenl wilh overlying skin ul~ ceralion ro prostralion and dealh. A small ulccratcd pustule ringcd by a rosy rash is seen on Ihe lowcr cxrremities of some of Ihe crew. Wilhin days. more rhan one half of the populalion of Ihe port cilY are dead. Which of lhe following agenlS is most likcly res¡xll1sible I"or Ihe rapid spread 01" Ihis disease? O (A) Mosquiloes O (B) Rals O (C) Sand flies O (O) CaL<; O (E) Tich

For each of the palienl histories in queslions 32 through 37. malch Ihe most closely associaled lettered infec¡ious agem: (A) (B) (C) (D) (E)

Adcnovirus

Aspergilllls fumiga/us BacteriodesJragilis Campylobacter jejllni Candida alhicans (F) Coccidioides immiti.f (G) Coronavirus (H) Corynelxlcferium diphtheriae

(1) Coxsackicvirus (1) Enlamoeba Ilütolytica (K) Herpes simplex virus (L) Histoplasma capSUÚIlllfll (M) MI/cor species (N) Mycolxlcterillfll fllherCIIlm'is (O) Neisseria gonorrhoelle (P) PsellllomonLL~ aemgin()sa (Q) Pnellfllocysfis carinii

(R) ROlavirus (5) Stre/Jtococcus pnellflloniae (T) Toxo/Julsma gondii

32. A 25-year-old I"emale has had pclvic pain, fever, and vaginal discharge I"or severaJ weeks. On physical examination. she has lower abdominal adncxal tenderness. She also has a painful, swollen knee. ( ) 33. A 19-year~0Id fcmale is admittcd wilh a 2-day hislory of severe righl facial pain. 5he ha<; righl eye proplosis. Laboralory findings indude 4+ kelones on urinalysis and a scrum glucose concenlralion of 475 mg/dL. She becomes oblunded. ( ) 34. A 6-month-old infanl developed diarrhca of 2 days' dumtion. This resultcd from villous atrophy proouced by invasion arKI destruction of the intestinal epiLhelium and resultanl decrease in absorplion of sooium aOO water. ( ) 35. A IO-year-old girl with severe neutropcnia 1 month aftcr bone marrow transp1anlation devclops fever and difficulty in brealhing. A chesl radiograph SUggesls pulmonary

INFECTIOUS DISEASES

69

infarels. Al autopsy. pulmonary vessels are occluded by abundanl growth 01" microorganisms.. ( ) 36. A palienl with eXlensive burns in the surgical itltetl~ sive care unit develops neulropenia and bilateral pneumo-nia. Al aulOpsy, the lungs show palchy areas of conso\idatiOIl. Microscopic examination reveals pulmonary vasculitis and surroundillg arcas of necrosis wilh sparse inflammalory exudale. ( ) 37.

A 50-year-old resident of Phoenix. Arizona. who

n..'Cently moved to DalIas. Texa<;, presenls with a cough.

A chesl radiograph reveals a 3.5-cm opacity in the right apical region with cenlral cavitation. An open lung biopsy is done lo excludc cancer. Microscopic examinalion reveals ca<;eating granulomatous inflammation conlaining large (60-p.m) spherulcs filled with smaller, roundcd slruclures. ( ) 38. A watery diarrhea is causing dehydration of a l-yearold child. Examinalion of a slool specimen by enz)'me immunoassay reveals Ihe presence of rolavirus. The child is given intravenous ftuids and makes a complete recovery in a week. Which of the following mechaniSIllS accounts for this diarrhea?

O (A) Decreased absorption of sodium and waler O (B) 1nereased secretion of sodium and water by epithe~

lial cells

O (C) Prcsencc of Yop virulenee plasmid O (O) Lysis of colonic epilhclial celis

O (E) Decreased breakdown of lactose lO glucosc and galaclose 39. A 5-year-old girl devclopcd a blotchy. reddish brown rash on her face, Irunk. and proximal cxlremilies over 3 days. On physical examination, shc had 0.2~ lo 0.5-cm ulccratcd lesions on Ihe oral cavity mucosa. 5he also de~ veloped generalized Iymphadenopathy. A oough wilh minimal sputum production then progressively worsened over Ihe nexl 3 days. Which of Ihe fol1owing infectious diseases did Ihis child mOSI likely have?

O (A) Mumps O (B) Varicella zosler virus (VZV) infcctiotl O (C) Rubella

O (O) Mononuclcosis O (E) RubL'Ola (measles) 40. A ehronic abscessing pneumonia of Ihe right middle lobe appears on Ihe chest radiograph 01" a 42-year-old maJe known to be HIV positive. A tmnsbronchial biops)' reveals Ihe presence of gram-positive filamentous organisms Ihal are weakly acid I"as'- His course is further complicaled by empyema and acule onsel of a headache. A head cr sean rcveals a 4-.em diserete lesion or Ihe righl hemisphere wilh ring enhancement characteristic of an abseess. The ¡nfce· lious agem masl probably responsible tor these findings is O (A) A~'1Jergilfllsjumigatl/s O (B) Nocardia m"teroides O (C) Mycobaclerillfll avillm-intraceilu/are


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70

o (D)

Part 1

GENERAL PATHOlOGY

StlIphy/ococcl/s O (E) MIlCOr spedes

allrellS

41. A 33-year-old fcmale who i~ an injL"Ction drug uscr dcvdops a sevcre hcadache and ncck sliffncss. She ha" no papillcdcma, and a lumbar puncturc is pcrfonncd. A Gram stain of the CSF obtaincd TC\'eals many soor1 gram-positi\'c rods. How wa.. this infectioll lnost likcly to havc bf.:cn aajuircd?

transfcrasc aOO al.anine aminotr.msferase C04lCCntrations. but his scrum bilirubin levcl is ro c1evalcd. A liver biopsy is pcrformcd. aOO the sample ha" lhe mieroscopic appcarance as shown in !.he figure. An acíd-fast stain of Ihis tis.'me is pusiti\'c. By which of lhe foUowing mechanisms is lhe infectious agcnt heing destruycd? O (A) Phagocytosis by cosinophils O (B) Elaboration of nilrie oxide by macrophages

O (C) Gcner<llioll of NADPH-dcpcOOenl oxygen-frL'C mdicals

O (A) Sharing infoctcd nL'Cdles

O (8) Inhalation of drop1c1 nuclci O lC) Inoculation through a CUI on thc ski n O (D) Eating conlaminatcd dairy products

O (O) Complclllclll-mcdiated Iysis O (E) Supcroxidc fonnalion withill phagolysosomcs

O (E) Using a friend's loothbrush 42. A 6-ycar-old boy dcvcJopcd a rash over his chest that slartcd as O.5-cm·diamctcr. rcddish macules. In a day or so, the macules bccalllc \·csidcs. A fcw days laler, Ihe \'estclcs rupturcd and crustcd overo CJOps of ¡hese lesions spread to involve lhc faec and thc cxlrcmitics over lhe ncx! 2 wccks. Dccadcs later. which of Ihe following manifcslatiorui of Ihis infcclion is most Iikcly lO appcar'! O (A) Shingles O (8) Infertility O (C) Paralysi.<¡ 0(1)) Congcslive hC,lrl failure O (E) Chronic arlhrilis

43. A 6-ycar-üld child prcsented wilh 7 days of diarrhca. A stool culture was positivc for Shigella spp. What would yoo cxpcct lo !iec in an cndoscopic biopsy of lhe colon?

O

(A) Epilhelial disruptiun with an o\'erlying exudale of

O (B)

O (C) O (D) O (E)

polymorphonuc!ear Icukocytcs (ncutrophils) Mulliple granuloma<¡ thruughout lhe wall of thc ":010" Slighl incrca..e in lhe numbcrs of Iymphocylcs and plasma cclls in Ihe lamina propria Illlranuclcar illclusion.<¡ in !.he cnterocyles Exlcnsi\'c scarring of the laminll propria with Slriclure formatioll

45.

A 23-year-old female patienl ha<¡ had recurren! vesicular genital Icsions for SL'vcral )'ear.i. A genital mucosal Icsion is dcpictcd microscopically under low power as shown herc. MKroscopic examinatioCl under highcr magnification of Ihis Icsion is likcly lO m'eal

O

(A) Dyspla"lic t.1'ithc1ial cclls Ihal oonlain human papil-

lomavirus sc..'qucllccs O (8) Ncutrophils containillg ingeslcd gmm-ncgali\'c diP'"

loc.:occi Mullilluclcatcd (syncytial) cetls thal COlllain pillk-topurple il1lr<llluclear inclusions O (D) Pcrivascular lympooplasmac)'lic in'¡ltrale SUfTOUOOing arterioles. wilh cooOlhelial proliferalion O (E) l\'lononuclear infiltrate with Tric/lOmOflos l'ORilUllis or-ganisms

O

(e)

For cach of lhe palienl historics in qucstiOllS 46 aOO 47. match the most c10scly associalcd leuercd c1inical finding TCl'iulting fmm an infectious diseasc proccss: lA) (B) (C) (D) (E) (F)

4-1. A 32-year-old malc has had a fever wilh wcight loss over lhe pa.'" 3 monlhs. He has clcvatcd a"partatc amino-

(G) (H) (1) (1)

Cerebral absccsscs Chrollic anhritis Dilated cardiomyopalhy Eleph,mliasis Hcmolysis Hepatic fibrosis Lcg paralysis Meningitis Mucocutancous uleen; Myositis


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Chapler 8

(K) Paranasal bollY deslruclion (L) Skin anesthesia (M) Squamous cell carcinoma (N) Slillbirth (O) Voluminous walery diarrhea

46. A 45-year-old rice fanncr bccomcs infecled by cercaria that penelratc lhe skin of his feet lbc ccrcaria are released from snails living in the irrigalion canals. He develops progressive asciles. ( ) 47. A 9-year-old child living in a mud hut in northeastem Brazil is bittcn by a rcduvid bug. aOO an erythemalous nodule develops al 1he comer of hcr lllouth. Several ycars later. she has worsening dyspnea. ( )

INFECnoUS DISEASES

71

49. A 45-year-old male with a long history of gastroinlestinal reflux discase aOO 8alTCtt esophagus is undergoing chctTl(lChl..'rapy for adenocarcinoma or the esophagus. He bccomcs sc\'erely neuLrOpcnic. wilh a white blood ccll counl of only 501p.L He thcn de\'c1ops a cough aOO fever. A chesl radiograph te'o'eals multiple 0.5- to 2-cm nodules scauercd Ihroughout all lung fields. He has a hcadache and acutc-onset seizure disordcr. A head cr sean reveals a 1.5cm. foundcd mass in lhe right parielal lobe. A biopsy of a l-cm ulccrated mass involving his right nasal septum is shown at the boUom of the lefl column microscopically with a silvcr stain. ( )

For eaeh of the clinical histories in questiotls 48 through 51. match the mosl cJosely associatcd infectious discasc: (A) African trypanosomiasis (B) Amcbiasis (C) Aspergillosis (D) Chagas discasc (E) Cholcra (F) Dengue fever (G) Filariasis (H) H)'datid discase (O leishmaniasis (1) leprasy (K) Lyrne discasc (L) Malaria (M) Plague (N) Schistosomiasis (O) SyphiJis (P) Tetallus (Q) Trachoma (R) Tutx:rculosis (S) T)'phoid fevcr

48. A 25-year-old femalc has a suddcn onsel of a scvcrc. voluminous. watel)' diarrhea. She !x.X:Ollles scvercly dehydrated over the nexl few days. Microscopic cxamination of the diarrhea fluid reveals flecks of mucus but no blood and few whitc blood cdls. A blood culture is negative. She recovers in hospital with inlravenous fluid lherapy over the nexl weck. ( )

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SO. A 32-year-old malc has dcvdopcd maculopapular aOO nodular skin lesions, mainl)' ilnrol\'ing his face. elbo....'S. wrists. and knecs. 1lle nodular lesions ha\'c slowly cnlargcd over Ihe past 10 years aOO are now bcginning to cause dcformily. Howe\'er. thcsc lesions are not painful; he has dccreased lO abscm sensalion in (hesc areas. A biopsy is laken of a nodular lesion aOO shown hcre with acid-fast stain. ( ) 51. A 44-year-old femalc nOliees an crylhematous papulc on hcr left 10\Ver leg thal bccomes a ringlikc rash lhal subsides over scveral wccks. Over Ihc nexl 5 momhs. shc has millratory join1 and musc1e pain. She has substernal chesl pain and an irregular heart rhythm. These problcms slbside. oot 2 years after the initial rash appeared. she has a chronic arthritis in\"olving hips, knees. and shoulders. ( ) 52. A baby bom at term is sl..'vcrc1y hydropic. Thcrc is a diffu....e rash with sloughing skin on palms and soles. Wilhin 2 days. the nconate is dcad of rcspiralOry dislress. Autopsy revcals markcd hcpatosplcnomegaly. There is a pcriosleitis aOO osteochondrilis. 'Iñc lungs are pale and poorly aeralcd, with imcrstitial mononuclear infiltrales. Scrologic tests for which of thc following is lnost likcly lo be positivc in the baby's mother? O (A) HIV

O (B) Herpes simplcx. typc 2

O (C)

TOX01Jlasma gondii

O (D) Syphilis O (E) CYlomcgalovirus


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GENERAL PATHOlOGY

ANSWERS 1. (A) He has cryptococcal meningoencephalilis. a eomplication of his immunocomprocnised state. C. neofonnans typically has a Ihick capsule. maling it easily visible with Ihe India ink preparation. a procedure that takes only a few minutes to perfonn. The CSF glucosc and protein 1c\'c1s can aid in determining whell'ler an infection is prescnl and what general type of orgallism is presento but they do not yield a specific causc. A cryptococcal anligen test would be useful for this patiem. Brain biopsies are not eommollly done. and ()(hcr Icss ill\'asive methods should be pursued firs!. A bacterial meningitis is possible. and pneumococcus would be a common bacterial cause. bul the descriplion here is that of cryptococcosis. PCR probes fOl" EBV are not useful in this case. because an acute viral meningitis does not usually cause a \'isible exudate. lhe OlIset of discase is more insidious. and it is not typically associatcd with immunocompromised states.

BP6

n7

PSD6379-38O

2. (q Amebie liver abscess is an uncommon complicalion of amcbiasis. 11le colonic lesions are Iypically gone by Ihe lime lhe liver lesions appear. E. 1listol)1ica organisms can invade the colonic submucosa. gaining access to \'enulcs drailling lO lhe portal system. Giarrliasis is caused by an intestinal parasite that causes a watery diarrhea. Typhoid fever is a sySlemic disease that produces splenomegaly more so Ihan hcpatornegaly. and abscesscs are not commono ÚJmpylobacrer and Yersinia can produce various prescntations of diarrhea, but abscesses are unexpectcd.

BP6 269, 496 PBD6358-359 3. (O) Syphililic chancres occur in lhe primary slage of syphilis and are eharaclerized by lymphoplasmacylic infiltrates along with an oblitemtive cndartcr"llÍs. Similar \csiolls may alw appear with secondary syphililic Illucocutaneous lesions. Caseating granulommous inflammatioll is more chamclcrislic for tuberculosis 01' fungal infections. Acule inl1ammation wilh abscess formation is characterislic of baclerial infections such as gonorrhea. Gummalous illflammation can be seen with lertiary syphilis in adulto; or in cOllgenital syphilis.

BP6589-592

PBD6 346,362-364

4. (C) Rhinovirus binds lo ICAM-I and accounts fOl' 60% of common colds. M. pnelUnolli(le also aa::ounts for some colds. bul Ihis agent docs not btnd LO lCAM-1 recep-tors on host cells. H. injfllenZlle can produce sinusitis, otitis media. and bronchopneumonia. EBV infecrion can produce pharyngitis with infectious mOllOllucleosis. but the counoe leoos to exlend over wccks. N. meningitidis infections P"' ducing meningilis may begin as a mild pharyngitis, but lhese infeetions can have a very mpid COllrsc OVCT I DI' 2 da)'s.

and dissemillme hemutogenously, oflen sctlling in gray and white cerebral tissue, where they devclop illto cysts.

PBD6395-396 6. (L) Poliomyelitis is un enlerovirus sprcad Ihrough fecal-oral conlaminatioll. The virus infects the oropharynx first. It ttJen sprcads tO spinal con! anlerior hom cells aOO bulbar nuclei to produce the paralysis typical of polio. Vaccination has made this diseasc rareo

PBD6373 7. (G) This is visceral lcishmaniasis. or kala-azar. Leishmaniasis is endemic in the Middle East. South Asia, Africa, and Lalin America. The organisrns proliferate within macrophages in lhe mononuclear phagocyte system and cause hepatosplenomcgaly and Iymphadenopathy. Often, lhere is hyperpigmcnlation of lhe skin. Bone marrow in\'clvemcnl and splenic enlargemellt contribute to reduced produetion and acceleratcd destruction of hematopoietic cclls, giving rise to pancytopcnia.

PBD6 391-392 8.

(A) Infeaion ....rith Chlamydin lrachomatis is one of more common sexually transmiued discascs. bol most cases have only urethritis and cervicitis. Howc\'er. sorne Slrains of C. trac/Il)ttlntis ean produce Iymphogranuloma vencrcum, a chronic. ulcerative discase Ihat is more endemie in Asia, Africa, and Ihe Caribbean. There is a mixed granulomatous aOO oeulrophilic inf1ammatory reaclion. In contrdSL, herpes simplex virus produces clear mucocutaneous vesiclcs with no exudatcs and is unlikc1y lO involve Iymph nodes. Recurrent Iymphoma has sheets 01' nodules of pleomorphic Iymphocytes wirhout significant inf1ammation. Candidiasis can produce superficial inf1ammation wilh an exudate but is rarely invasivc 01' dissemillated in nonimmunosuppn.:ssed individuals. A variely of bacterial infec· tions Ill<lY involve lhe vagirm. (he

BP6595 PBD6361-362 9. (B) This pllliellt has high HIV-I RNA levels that are consistenl with Ihc diagnosis ol' acquired immunodeficiellcy syndrome (A1DS). Although patienls with AIOS are susceptible lo many microbes, infections with CMV arc partie· ularly common. This biopsy shows an elllargcd cell contaillillg a dislincl intnmuclear inclusioll alld ¡U-defined cytoplasmie inclusiOlls. This is typical of CMV infcctiOIl. EBV infc.:ction is frequelltly seen in paliento; with HIV infection, bUI lhere are no dislincl pulmonary lesions associated wilh it. Respirmory syncytial "irus infcctions are seen in childrell aOO rarely in adults. Herpes zosler infcetious are rnosl Iikcly lO affeel Ihc pcripheral ncI'VOUs system uoo can become dissc.:minate<1 to affect the lungs in immunosuppresscd palients. Adcnovirus is a common viral pathogen in adults thm may produce a c1inically significam pneumonia, aOO intranuclcar inclusions may be present. bul lhe cells are not large. aOO cyloplasmic inclusions are absen!.

PBD6 347-348

8P6429-430 PBD6 726

5. (M) He has c)'Slicercosis. Eating uncook:ed pork can result in !he release of larv3C lhat pcnetrate the gut wal1

10. (B) Amebiasis is a comlllOn cause for dysentcry in de\'eloping nalions. 'lbe E. histol)1icn lrophozoites can 31-


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Chapter 8

taeh lo colonic epithc1ium. invade, and Iyse Ihe epithelial cells. In sorne cases., lhcre can be cxtcnsive mucosal invol.vernenl wilh characlerÍSeic ftask-shapcd (i.e., like an EfIctUneycf ftask) ulcermions similar lO othcr scvcre inftammatory bowcl discascs. Giardiasis lends to involve the small inteSline with variable inftammalion bul withoul ulceralioll. Shigcllosis can pwduce a bloody dyselltery with irregular superficial colonic mucosal ulettation, bul the organisms typically do nOl invade bcyond the lamina propria Sahoonellosis more Iypicall}' in\'ol\'es the small illlestine and in nlOSt cases produces a sclf-limilcd cnteritis, although more Sf..'Vcrc disease with dissemination lo OIhcr orgam; can occur wilh S. tylJJ¡i infection. Cholera is characlcrizcd by a massive secretory diarrhea wilhoul inlestinal mucosal invasiol1 or nccrosis.

BP6 496 PBD6 358 -359 11. (B) The Sf¡jgelfa organisms el¡¡bomle a shiga 10xil1 thal damagcs colollic epithelial cells. The colonic mucosa is inlcnscly inflatm:d with uicenllions and pscudomcmbrane formalion (i.e., palc, white palchcs). S. jfexneri infections in persons positive ror HLA-B27 can ¡cad lo Reiter syndromc, wilh chrooic arthritis. Vibrio organisms c1abonlte an exotoxin and do not invade and dcstroy intestinal epilhc¡ium. E. liistof)'tirn can pnxI.uce a bloody diarrhca hut not Reilcr syndmme. Typhoid fever has many systcmic problems bul not arthritis. H. pylori living in gastric mucus drivcs lhe processe.<¡ of chronic gastritis and ulceration of gastric and duodenal mucosal surfaccs.

BP6 495 PBD6 355 12. (E) She has diphlhcria The C. diplltlu!riae organisms proliferale in lhe inflammatory mcmbrane Ihat CO\'CB the pharynx and lonsils. These organisms c1aborale an cxotoxin Ihat produces myocarditis and neuropalhy. 'Iñc organisms do not disscminale lo cause inflamnuuion or ahscrsscs or v3SCulilis elsewhere in the body. Endotoxins tend lO be elaboraled by gram-negalive baclerial orgallisms. Granu~ 10malOus inflml1l11ation is more Iypic<ll for mycobacleri<ll al1d fungal infedions.

BP6274 PBD6343,759,1276 13. (A) Hc has Rocky Mounlain spolled fever, which occurs sporadically in lhe UnÍled Slates in piares olher lhan Ihe Rocky Mountains. Rickellsial diseases produce signs an<1 symploms fmm damage to vascular endothelium and srnooth muscle, similar lO a v3SCulitis. Thrombosis of lhe affcctcd blood vcsscls is responsible for foci of skin necrosis. Hansen disease, produced by M. feprae, results in skin ancsthesia lhal predisposes lO recurrcnt injury. Plague. causcd by Y. pestis, can produce focal skin necrosis at the sile of a !lea bite. Lymc discasc, produced by B. bllrgdorferi, can produce an Cfythcma chronicum migmns of skin at the sile of a tick bile. MucQCulancous leishmaniasis mainly involve$ the nasal and oral regions.

PBD6 384 14. (E) This rash alld edema are lIlanirestation.~ of streptococcal erysipelas. Erysipelas is usualJy causcd by Iypes A or C of StrefJltJCocclI.~. Streptolysins elllboralcd by Ihcse organisms aid in the spread of Ihe infection. C. bOllllinum

INFECTIOUS DISEASES

73

c1aborales ao eXOloxin thal whell ingesled results in paraly~ siso E. coli produces a variely of infcctions, but skin infee-tious are not commc>n. N. gonorrlloeae is ~ Imown as a scxually transmiucd disease, and a rash is possible, although usually without pronounced sweJling. S. epidermidis is usually considcred a contaminant in cultures.

PBD6367-368 15. (O) The influenza pandcmic in 1918 rcsulted from an anligenic shift in Ihe influell7.3 A I)'pe. This occurs when tbere is rerombination wilh RNA sequcnces of influenza viruses found in animals such as pigs. Mutations in the el1\'elope gencs are responsible for epidemics. These mulations allow eva~ion from hosl anlibodies. Influenza viruses do not bind to ICAM-I receplors; rttinoviruses do. Viruses do nO! make exotoxins and do TlOI acquire antibiotic resistance. A swille ftu virus has bt.'Ctl discovercd a~ a cause for the 1918 palldemic.

PBD634B 16. (C) 8acterial infeclions are marked by suppumtive inflammation, and a virulem organism such as Klebsiella can lead lO lissue destrudion with nbscess formation. Gasfonning bacteria, sueh as Cfostridillnt organisms, ate UIIusual respiralory infeclions. Granulomatous infiammation is charactenstic for mycobaclerial or fuogal infectjol1S. InfectiOllS of the lung do not resull in emph)'sema Carcinomas are nO! sequclae of bacterial infections.

BP642B-429 PBD6345 17. (A) AClinom)'cetes tbal can produce chronic abscess~ ing pncumonia, particularly in immunocompromised palicnts, include A. israeli and N. asteroides. Sulfur granules, formcd fmm masses of lhe hrdnching, filamenlous organlsms, are more likeJy lO be seen with Aclinomyces. B. dermatitidis infectjons lend lO produce a granulonlalous ínflammalOl')' process. Chlam}'dial infcctjollS produce an interstiti<ll paltem, jusI likc mosl viruses. Klebsid/a infeclions, as other baclerial infeclions. can result in abscess fonmltion, lllthough withoul dislincl sulrur granules. M. kllnsasii infections are similar lO M. tllherCll/osis infections in lhal gnmolomalous illflarnmation is promillcnl.

BP6 420

PBD 335, 722

18. (B) Aflcr the infective mosquilO bite, P. fa/áparum sporozoiles invade liver cclls and reproduce asexually. Whcn lhe hepalocytes rupture. they release thousands of mero7.oitcs that ¡nfeet red blood cclls (RBCs). 11le infecled RBCs circulatc. These infected RBCs can bind lO cndothelium in brain, and small cerebrdl vessels bccome plugged with the RBCs, resulting in ischemia.

BP6352-353 PBD6 3B9-391 19. (A) S. ilematobillm is secn in Africa, particularly thc Nile Valley, in ateas whcre inigaüon has cxpanded !he range of Ihe hast snails. Jt infects the wall of thc urinary bladdcr, causing scvcre granulomatous inftammalÍon, fibrosis, and calcification. T spirali!>' infects strialL'C! muscle. Cysticercosis can have a wide lissue distribution, bul bruin is I110SI oflen affecled. Mycobaclerial inteclions of lhe urillary tracl are Ul1common and do not CllUse bladder fibmsls.


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11J>OJIiUD'l I >

GENERAL PATHOlOGY

Ascaria..is involves Ihc 10wcr gastrointestinal lract. alld Ihc worms reside in Ihe lumcn.

PBDó 396-397 20. (O) M)"coplafnw infL'(;tions Icad lo a primary atypical pncumonia in which there are no ah'l.:'01ar infillrates. but Ihcre is prominenl inlcrslitial inflammation. Alveolar and bronchiolar ncutrophilic cxudalcs suggest a baclerial agenl causing pncumonia. Granulomas with Langhan.c'-IYpe giant cells arc t}'pical for tuberculosis. Prolifcration of microorganisms wilh vascular occlusion aOO infarcLion is most l}'pical for Aspergilllls fungal infcclions. An empyema suggeslS a baclLTial cause for pncumonia with spread 10 pleura.

BP6419-42O PBDó 335.721-722 21. (A) Toxoplasmosis is the "T' in the TORCH mne-. monic for congcnilal infcetions (toxopla..mosis. other infce.tious. robella. C)101ncgaJovirus infcction. and herpes simplcx). lbc T. gnndii organism... can eross the placenta lo affect lhe felus. 1ñc mOlhcr is Iypically asymplomatic. The cal is lhe nalural hosI for T. gondii.

PBD6382-383 22. (E) Hcmorrtlagic fcver. or Denguc fever. is causcd by an arbovirus of Ihc Aavivirus group. This organism can be dcvaslaling bccausc il produccs bonc marrow supprcssion and becausc any anlibodies lo lhe virus enhance ccl1ular vinll uptakc. 11 is Imnsmitlcd by Ihc mosquilo ,·celor Aedes aegYI)ti.

PBDó 383 23. (O) Hc has tctanus. The contaminalion of a wound wilh C/ostrid;um tellmi CHn rL"Sult in lhe daboralioll of a polent lIeuroloxill. This loxin is a protease Ihal c1eaves sYllaplobrevin. a nllljor trdllSlllcmbranc prolein of thc synaptic vesiclcs ol" lhc inhibilory lleurons. The loxin of s. allrefl.f produces an elllcrOloxin thal aelS as a supcranligcn and slimulales T-cel1 cylokine rclease. Cholcra is produccd when Ihe loxin c1aboTllled by V. dIO/eme slimulalCS epilhelial cel1 Hdenylmc cyclllse. C. lJeljr;ngens elaborales a variely of loxins, one 01" which (Ietanospa<¡min) is a phosphulipase.

PBDó 368 -369 24. (C) ll1e original oUlbreak for which lhis discasc was named occurrcd al an American Lcgion convention. L pnellmol)/¡ila is a facultative pardSile of macrophages. A high mlio of macrophages (O neulrophils i... charaeterislic of the infeclion. Persons wilh immunosupprcssion arc al ri"k for CMV and Pnellmoeystis pncumonia. B. cepaáa is mosl oflcn seen in palicnls with cyslK: fibrosis woo ha'·e exlcnsi\'e bronchiL'Cla..is. L monocytogenes can prOOuce a disscminalcd diseasc wilh meningitis in immunocompromiscd adullS.

BP6418 P8Dó 377-378 25. (O) lbcsc largc, gram-¡:x>silive rod.. arc characterislíc of C. perfringens, which can contamLnatc open wounds and

produce ga<¡ gangrcnc. Candidal illfections are Iypica!ly superficial, alld a Gram slaín shows gram-positive buddillg cclls wifh pscudohyphac. Lisleriosis can be a congenital or food-bornc infoction. and Ihe organisms are lihon. grampositÍ\'e rods. H. inftllenzae is a gram-ncgative rod kllown besl for respiralory and CNS infcctiolls. B. fragilis can conlarninalc surgical wounds of fhe abdomen.

PBD6369 26. (O) Thc small )'ea..1S of H. capSll/alllm are often inlraccllular. InfccliOllS can be disseminalcd. ill\'Olving lissucs of lhe mononuclcar phagocYlc system. In lhe lung, histopla..mosis can mimic primal)' or sccoOOary luberculosis. Thc sphcrulcs of C. alb;collS arc l8Jt!cr aOO are llOI illtJa-cellular. C. neofomlllllS organisms have narrow-bascd budding and a~ lwO lO tbree times l8Jt!er t.han H. capSll/aJlUn organisms. Organism.. of B. denllatit;dis exhibil broadbascd budding aOO are slightly largcr lhan C. neofonllLJJU organismo¡.

BP6425-426 PBD6352-353 27. (E) This is c1cphanliasis. which rcsullS from Iymphatic obstruelion when therc is an ínflammalory reaction lO lhe adult filaríal worms Wllc/¡ereria bancrofti. Schistosomiasis may affect Iivcr or bladdcr most scvcrely. EchinocOCC14s prOOuccs hyd..1lid disca"e of liver. lungs, or bone. Tr;chinella encys!S in slríatcd rnuscle. ú;S/¡"'CJ!l;a can in\"Olve Ihe skin wilh ukCrdlion and enlargc parenchymal organs.

PBD6 397 -398 28. (A) Thc findings arc consislenl wilh African trypanosomillsis. or skcping sickne~. 'Ine eradication of the !SeISe Ry vL'Ctor has becn a priorily for dccadcs. Filarial worms elldemic in part... of Ccntral Alllerica, Soulheasl Asia, and Polyncsia can also appcar in blood but are smallcr in size and do nOl Icad lO chronic wasling.

PBD6 337. 393 29. (E) This is 11 small "coi n Icsion" of thc lung produccd by a granu10lmllUus innarnmalory process. One cause for Ihis procc...s is illfeelion with H. cupsu/atum. Bird droppings. eSlx:cially from pigeons. are a rich souree of dusls cOlllaminaled wilh H. capslllatllm. Fungal and mycobaclerial infeclions are nOl acc.¡uircd by trnnsfusion or olher parcnteml roules. such as sharíng inlrdvenous needles. COlllaminatcd mil k is a sourcc for Mycobncterium b0l1is. but Ihis is arare puhnOllal)' infcclion. Mosquitocs are nO! generally known as vL-clors for diseasc... Ihal cause granulomatous inflammalioll.

BP6425-427

PBDó 352-353

30. (B) TL'Sling for hepatilis B and C is pan of routinc screL'1ling of blood donors. This fonn ol" transmissiou for hepaLili... B is mosl common in dc\"c1oping nations. E. coli can be a congcnilal infcction. bul il lcaves no major significanl lasLing scquelac in infanl.. woo survi,'e. Malaria. candidal infcclion, aOO pncumoc)'slosis are nol c.ongenítal infeclions.

BP6 526 PBD6 339


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Chapter 8

31. (8) This incidenl was lhe beginning of Ihe Black Dealh in Europe lhal persisle<! Ihmugh lhe 14th and 15th cenluries. Rodents forro the reservoir of infeclion. Aea bites and aerosols transmit lhe infection vel}' efficicntly. 'Iñc causalh-e organism, Y. pestis, secreles a pla'iminogcn activalor lhat promotes i1s spread. Plague was eodcmic in Easl Asia al the beginning of Ihe 20th cenlury and was carried lO San Fmncisco. Noc wanling lO produce a panic tha! could be bad for business or 10uriSI1l, California's governor al Iha! lime did not enforce a (IUamntine. As a consequence, plague is endemic in wild rodenls in Ihe western Uniled Slales, bul il forlunately accounls for only occasiOllal sporadic hUIl111n illt<:ctions,

PBD6387-388 32. (O) She has pelvic innammatory disease. which may be produced by gonococci or Chwmydia. N. gonorrhoeae aOO Chwmydia are sexually Irnnsmiued diseascs. Complicalions of pelvic innammalory disease includc perilonitis. adhcsions wilh bowel obslnJclion, sepsis with endocarditis. meningitis, arthritis. and infenility.

BP6 593.613

PBD6 362

33. (M) Rhinocerebral rnucormycosis is a feared complication associaled wilh diabetic ketoacidosis. The broad, nonseplale hyphae illVllde eXlellsivcly illto paranasa[ sinuses and orbil and illto Ihe ccntr'.tl nervous syslem.

BP6428 PBD6380-381 34. (R) Rocavirus, an encapsulatcd RNA virus, is a major cause for diarrhea in infancy_ 1be villous deslruction wilh atrophy leads lO decreased absorption of sodium aOO waler. 1ñe de\'elopmenl of anlibodies fmm secretory immunily in lhe bowel lO rotlwirus surface anligens makcs older childrcn and adults relali\'ely resislant to rotavirus illfection. Such anlibodies are presenl in maternal mil k élnd confcr some dcgree of resiSlance lo babies receiving rnolher's milk.

BP6493-494 PBD6354 35. (B or M) Aspergill/ls, CllIUlida, and Mllcor infecliolls may become disscminated in lhe setting of ncutropenia. Vascular invasion can occur \\~th fungal infections, particularly wilh Aspergilll/s and MI/cor. After lhese organisms gain a foolhold (hyphac-hold) in lissucs, Ihey are very difficult lo eradicale.

BP6428 PBD6380-381 36. (P) P. aemginosa organisms secrelc severa! virulcllce faclors: exotoxin A, which inhibits prOCcin synlhesis; exoenzyme S, which imerfcrcs with host cell growth; phospho-lipa"e C. which degrades pulmonary surfaclallt; and ironcolllaining compoullds. which are toxic lo endothclial cells. These viru!l.'11Ce faetors resull in eXlensive va<;culilis wilh necrosis. Neutropellic patlents are particularly al risk.

BP6418 PBD6 376-377

INFECTIOUS DlSEASES

75

37. (F) Inhaling lhe arthrospores of C. immilis can lead to coccidioidornycosis. This disease is endemic to the soulhwcslcm Uniled Slales. 1ñe infection typically results in granuloma formatiou. bul most perrons have subelinical infections. About 10% lila)' be symptomatic with respira101)' symptoms, including cough aOO plcurilic chesl pain. DisseminaLion lo eXlrapulmonary sites occurs in only 1% .or cases.

BP6 427 PBD6 353 38. (A) Many emeroviruses produce diarrhea by inhibilillg Ihe intestinal llbsorplioll or imra[uminal sodium and waler. Mast older childrcll alld adults have immullilY. Cholcm is Ihe result of secretioll of an exotoxin by Ihe V. clioierae organismo which potelltiates lhe epilhelial cell produetion of adenylale cyclase aOO causes secrelory diarmea. 1ñe Yop plasmid confers infectivity lO Yersinia organisms. Amebae can Iyse cpilhelium, and lhe diarrhea can be bloody. Decre.ascd breakdown of laetose occurs in disaccharida'iC deficiency and gives rise lO an osmotic diar-

mea.

PBD6 354. 815 39. (E) lñe rash and Ihe Koplik spotS on lhe buccal mucosa are charaCleriSlic findings for measles, ,\ childhood infeclion. Il occurs ollly sporadically whcll immunizations havc been administered lO a large part of lhe population. 'Iñe severily of Ihe ilIness varies, and a measles pneumonia may complicale lhe course of mis disease, whkh in sorne cases can be life Ihreatening. Mumps produces a paroIitis and an orchitis. VZV infeclions in children manifest as chickenpox. Rubella, also called German measles, is a mueh milder infection lhan rubeola. Mononucleosis resulting from EBV infeclion is more likely to occur in adolescellce.

PBD6 370 40. (8) Allhough nocardial infections Iypically slart in Ihc lungs, Ihcy often becomc dissemimlled, particularly lo Ihe cenlra! nervous system. These infections are mosl oflen seen in immunocompromised palienls. Aspergillosis can also affeel ~rsons wilh immune compromise. but Ihe fUIlgal hyphae are easily dislinguishablc on hcmatoxylin aOO casin stains. M)"cobaclerillln avillm-intracelfu/are infections are seen in persons wilh AJOS, bul lbese are short. addfasl rods tha! produce poorIy fonned granulomas. Bacterial pneumonias should also be considered in immunocompromised paticnLs, and septicemia can complicate lhem. bul S. OllrellS organisms fonn c1USlcrs of cocci on Gram stain. Mucar organisms huve broad, nonseplate hyphae and are scen mosl commonly in diabelics and bum palients.

BP6 420 PBD6 334. 722 41. (O) The resull of lhe Gram stain is diagllostic for L monoc}'togenes, an organism more likely lO produce disseminaled disease in persons who are immunocompromised. These include injection drug uscrs, who are al u high risk for HIV infcclioll. üsteri05is is l10I known to be


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76

Part 1

GENERAL PATHOlOGY

acquircd p<ucntcrally, although it can be a congcnilal inftttion.

producc small blislcn;; or papules, bul mese are oflen sclflimilOO and oot typically recurTCn!.

BP6 726

BP6595-596

PBD6 37B

42. (A) 1ñc ski" Icsions are Iypical for chickcnpox, a common childhood infcction causcd by VZV inftttion. lhc infcclion can rcmain dormant for )'cars in dorsal root ganglia. only to reacti\'atc when immune status is diminishcd. InfcrtililY is a complicalion of lIlumps orchitis. Paralysis can complicalc poliovirus infcctioll. Rhcumalic hean discasc can appcar afier group A (3-hcmolytic streptococcal infcctiOIl. A chronic arthritis can be secn with Lymc dis· case after B. bllrgdmferi infcetion.

PBD6 373-374 43. (A) Shigellosis rcsults in a hloody dyscntcI)' bccausc thc ShiRella organisms can invadc and dcstmy the mucosa. TIlcrc is lypical1y a mononuclcar inlillratc cXlcnding to thc lamina propria with a ncutrophilic cxudatc ovcrlying thc ulccratcd arcas. Granulomalous inl1ammalion mal' be sccn with granulomalolLS colitis (Crohn discasc) and intestinal luberculosis (f3J"C). An incrcasc in lIlollonuclcar inAamllla· tory cclls may appcar wilh mi1da fonns of enlcrocolilis causOO by viruscs. Giardia. and So/mol/ella spp. Imranu· c1car inclusions in cnlcrocytcs poi ni 10 infcclion wilb DNA \·iroses. such as herpcsviruscs. SlriCturc formation may fol· Iow illtcstinal tuberculosis.

BP6 495

PBD6 355

44. (8) 11lis is a granuloma ActivatOO macrophagcs are the key cellular componelll wilhin granulomas. C04 ccJls secrele illtcrferon-y, which activatcs macrophages to kili organisms with reactive nitrogen imermcdiates. Eosinophils are nOl a major componen! of mo."l granulomas. and they cannot d~troy m)'cobaclcria. NADPH-dcpcndcnt rcactivc oxygcn spccics arc importanl in lhe l)'sis of bacteria by nculrophils. COlllplelllcnt mcdialcd l)'sis is not in"ol"cd in lhc dcstnlclion of illtraccllular baclcria such as M. IlIbercll' /osis. Howc"er. complcmcnt aclivalion on the surfacc of M. IlIbcI"ut/osis can opsollizc Illem for uptuke b)' macrophagcs. M. IIIbel"w/osis organi...ms rc... idc in phagosomcs. which are nol acidifiOO imo phagolysosolTlcs. Inhibitioll of acidifica!ion is causOO by lhc urease sccl"Ctcd b)' IIl)'Cobaclcria.

BP6421-423

PBD6 349-35\

45. (C) 1his is a "csicle lhal has resullcd from herpes simplex \'irus (HSV) infectioll. Mest genital inrections are cau.<;ed by I-ISV·I, and HSV·2 is responsiblc for most cases of hcrpctic gingi"ostomatitis. nlC "iral cytopathic eITcct resulls in formalion of intranuclcar inclusions. multinuclcatoo cclls. and cell Iysis wilh \'csiclc formalion in Ihe cpilheliulll. Cervical dysplasias do nol produce \'csicular Icsions and are the result of anolher sexually transmiucd disca,<;e-human papilloma"irus infcction. Gram-negati\'c diplococci are characlcrislic for N. gOllorrllOeae ¡nfeclion. anothcr scxually transmittOO discasc. Lymphoplasmacytic infiltralcs lllay be SCCII wilh a chancre causcd b)' T. pallidI/m, lhe causati"c agcnt of s)'philis. Trichomonia..is may

PBD6360-36\

46. (F) Hc is ¡nfcctOO with S. IIIrmsOIli or Sclrislo.mma japmliclIm. Fcmalc worms in the ponal \'cnous s)'slem reIcase eggs lbat incite a granulomatous inflammatory rcaction in li\'cr. Wilh time. the portal gr.llluloma'l undcrgo librosis, compressing lhe portal \'cins. This gi\'cs rise lO sc\'erc ponal hypcncnsion, splcnomcgaly, and a'ieilcs.

PBD6 396-397 47. (C) She is infeclcd with TrYlxl1Io,mma erró. rcsulting in Chaga.. disca'iC. Thc orgallisms can damagc the hcarl by dirccl infeclioll or by inducing an autoimmunc response that affccts lhe hcart bceausc of the cxislcnce of cross· reaclivc antigcn. In 20% of infectcd ¡x:rsOIlS. cardiac failurc can occur 5 lo 15 years aftcr Ihc initial infcction. Thc affcclcd hcarl is cnlargcd, alld all four chmnbcrs are dilalOO.

PBD6 393-394 48. (E) TI'lC V. ello/eme organisms are nonin\'a..ivc. In· Slead. lhe)' producc sc\'cre diarrl'lCa by elaboration of an ellleTOloxill. called cholcra toxin. 'Illis toxin acts on bowcl mucosal cclls lO cause pcrsiSICIlI acti"alion of adcn)'lalc c)'c1ase and high Ic\'c1s of inlracclluLar C)'c1ic AMP thal dri"cs massi\'c secrction of sodium, chloride. and waler. 1l'lC fluid loss is life Ihrcatcning bccausc of resultant dchydr'dlion.

BP6495

PBD6 357 -358

49. (C) Noticc the scptatc branching h)'phac and a frtrit· ing bod)' l)'pical of Afpergi//I/s colony. Neulropcnia is a risk factor for dc\'c1opmcllt of aspcrgillosis. ln imlllun~ compromiscd palicnts. t1'lC various spccic... of Aspergifllls can producc sinusitis illld pneumonitis most frcqucntly. and disscminalioll lo othcr silcs such as lhc brain is common.

PBD6380-3Bl 50. (J) Leprosy, a1so knowll as HanSCll discasc. is causOO by lhe small acid-fasl organislll M. /eIJIYle. This organism canl10t be culturOO in artificial llledia. Diagnosis is by bioPS)' of a skin lesion. ThCI"C are lwo polar fomls of Icprosy: tubcrculoid and Icpromalous. In lhe luberculoid fonn. a dcla)'cd hypc~nsiti"ity rcaclioll gi"cs risc to granuloma· tous Icsion.... thal rcscmblc tuberculosis. Acid-fast bacilli are rarc in such IcsiollS. In contrasl. in the Icpromatous foml. shown in the figure. T-ccH immunil)' is mackOOly impaircd. and granulomas are tbcrcfore not fonnOO. Instcad. there are large aggregalcs of lipid-lillcd macrophages that are sluffcd with acid-fasl bacilli.

BP6 276 PBD6385-387 51. (K) 1be acutc stage of L)'mc discasc is markOO by lhc appcarance of cl)'thcma chronicum migraru; of the skin. As lhc B. burgdOlfá; orgallisms prolircrate and disscmitlate, systcmic manifcstalions of carditis. mcningitis, and migratol)' arthralgias and myalgias appcar. 11lis is foHowcd


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1!'flCT1OUS DlSEASES

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77

2 lO 3 yC3IS after initial infection by an arthritis of Iargc joims. BP6686-687 PBD6388-389

ter, early stillbirths do noI OCCUf. Most babics bom wilh HIV infection have 00 inilial gross 01" microscopic pathologic findings. Herpes infections in me neonate are usually

52. (D) These are lindings or congcnital syphilis. Because the spirocheles cross loc placenla in Ihe Ihird trimes-

00l initially obvious, because most such inrections are ac;quired by passage through lhe birth canal. Congenital IOX~ plasmosis and CMV pnx:luce severe cerebral disease. BP6592 PBD6362-363


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CHAPTER

9 Environmental and Nutritional Pathology BP6 Cooptar 8 - Environmental Oiseases PBD6 COOptet' 10 • Environmental and Nutritional Pathology

1. Sincc her early !\\'cnúcs, a 55+ycar-old fcmalc has beCIl steadily gaining wcighl. Shc is now 164 cm tall and wcighs 126 kg. Which of the following complicaÚons is shc leasl likdy lo dcvclop? O (A) Oslcoarthrilis

O (B) Endomctrial carcinoma O (C) Diabetes mellitus O (O) Pulmonary emphyscma O (E) Cholclithiasis

O (q Pyridoxinc O (O) Niacin O (E) Riboflavin 4. A 43-year'"Üld fcmalc has bccn taking oral conlraceptives for many ycars and has noticcd no sidc effccts. She is at a highcr risk than nonusers of dcveloping which of the following IUIl'lOn;? O (A) Endomclria! caneer

O (B) Hcpatic adcnoma O (C) Ovarian canecr O (D) Oallbladdcr canccr O (E) Pancrealic adenoma For cclch of the c1inical histories in queslions 5 and 6. malch lhc most eloscly associated disordcr rcsulting from a I\utritional dcliciel\cy:

2. A 30-yem-old male gocs on a diving expcdilioll lo thc BlllC Hole off the coa!>1 of Belize. Ovcr Ihc cOlll~e of 30 minutes, he dcsccnds to 50 mclcrs. whcrc hc bcgins 10 fcd light-hcadcd ¡llld disoriclllcd. Hc panics and ascends quickly lO Ihe sllrface. He soon cxpcricncc!> difhculty brcalhing, wilh dyspnea <lnd subslcrnal chcst pain. He Ihcn dc"c1ops a sc"cre hcadache <lnd venigo. The best cxplana+ lion for lhcsc lindings is

(A) Bcriberi (B) Blindncss

(C) Chcilosis (D) Diabetes mcllilUs (E) Ooiler (F) Hematuria (O) MacrocYlic anemia (H) Mara!>mu$ (1) MicrocYlic anemia (J) Pcllagra (K) Rickels (L) Scurvy

O (A) Hypot11cnnia

O (8) Dceomprcssion disca'>C O (C) Oxygcn loxicity

O (O) Multiplc conlusiolls O (E) Hypoxcmia 3. A 50-year-old maJc with a hislory of chronic alcoholism has hOO incrca...ing congeslivc hcan failurc for thc pasl year. For the past monlh, hc ha.. cxpcrienccd incrcasing oonfusion and disoriclltatiOIl, wilh difficulty ambulating. Hc is found on physical cxamination lO havc nyst:lgmm :lOO ataxia of gail. along wilh dccrca'>Cd scnsation in his lowcr cxtrcmitics. 1l1CSC lindings poinl lO a dietary dclicicncyof O (A) Folale

O (B) Uiamine

78

5. A 19-ycar-old pregnant fcmalc rc:t':civcs no prenatal care, cals a diet cOlllaining mostly earbohydratcs and fals. and takcs no prenalal vilamins with iron. 1ñe baby is bom al tcnn. bul the baby is palc and listlcss in the fi!"S1 wcck of life. Laboralory tesIs rc"caI markcdly dccrcased scrum fcrritin. ( )

6.

A 55-ycar'"Üld fcmale ha.. dcmelltia worsening o\'cr the past )'car. She also ha.. red. scaling skin in sun-cxposcd arcas. A watcry diarrhca has beco prcscnt for the past month. ( )


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Chapter 9 7. Al a party where a variety of drugs, legal and illicil, are being used, a 29-year-old prcviously healthy male sud~ denly coUapscf>. He is laken lO the hospital, requiring re· suscitation wilh defibrillation en route to eSlablish a normal cardiac rhythm. On admission, vilal signs show his lemperalure lo be 4ifC. respirations 36, heart rate IIO/min, and blood pressure 175190 mm Hg. His pupils are dilaled. Which of Ihe following drugs is most Iikely rcsponsiblc for these findings?

o (A) O (B) O (C) O (O)

O (E)

Ethanol Heroin Marijuana Phencyclidine Cocaine

8. A suicidal ingestion of 35 g of acelaminophen rcsults in symploms of nausea and vomiling in a 26-year-.old femaleo Within a day, which of the following laboratory test findings will indicate Ihe mosl severe organ damage?

o

(A) Hypokalemia O (B) Elevaled serum crcatine k.inase leve! O (C) Kelonuria O (O) Elevated scrum alanine aminotransferasc (ALT) level O (E) Hypcramylasemia

ENVIRONMENTAl

fl.ND

NUTRlTIONAl PATHOLOGY

79

forms of eleclromagnetic radiation p1ayed Ihe greatest role in Ihe development of Ihis neoplasm?

O (A) Ultnlviolct rays O (B) Infrared nlYs O (C) Visible rays O (O) X-rays O (E) Gamma rays 12. Several children belwccn Ihe ages of 3 and 6 have bcen admitted lO a loci.u hospilal for enccphalopathic crisis. ll1ey previously exhibiled retarded psychomolor devclopmento Head computed lomography (Cf) scans of Ihe chil~ drcn revcal marked cerebral edema. An investigatnr senl lo the housillg project where the childrell live fillds a rundown apartmcnt complex with extcnsive water damage, poor plumbing, lack of vemilation, and pecling. flaking pailll. Which of the lollowing IOxicilies besl accounls for Ihe findings in Ihcsc children? O O O O O

(A) (B) (Cl (O) (E)

Sodium hypochlorite Ethylene glycol Methanol Kerosene Lead

9. A baby born al Icnn has Apgar seOfC.<; of 8 and 9 al 1 and 5 minules. The baby is initially doing well. bul al 3 days of life. Iherc is blccding from Ihe umbilical cord stump. and ecchymoscs are observed over Ihe bultocks. This is followed by seizure activilY. Which of Ihe following nutrienl dellciencies besl aCCQums for Ihesc findings?

13. A dull Ihudding noise followed by Ihc sound or scrccching lires is Ihe signal for Ihe emergency departmcnl staff lo go outsidc Ihe hospital. Al Ihe door lO Ihe emer+ gency dcparnuelll. they find Ihe body of a young man who is alive but oblundoo. 111e examining physician notices that Ihe man has a pcrforaled nasal seplum, and a prominem callus is presenl on his right thumb. A head cr sean rcveals all acutc right frontal lobe hemom1age. He orders a sefllm drug screen, expecting 10 find

O O O O O

O O O O O

(A) (B) (C) (O) (E)

lron Yitamin E Folic acid Yilamin K lodine

(A) Cocaine (B) Opialcs (C) Cannabinoids (O) Amphelamine (E) Barbilurales

10. Sir Robcrt Falcon Scott reaches the Soulh Polc on January 17, 1912, barcly a monlh after Roald Amundscn achieved Ihis goal with his more expcrienced and prepared expeditionary party. ScoU's dejeclcd party must now make the long trip back to thcir base. bul Ihey are weak and running low on supplies. They finally can go no further, ironically only a few kilomelers from a eachc of supplies. They are found by a rescue temu, but lOO lale. Scott and his men are observed lO have a hypcrkeralOtic. papular rash, ecchymoses. and severe gingival swelling with hemorrhagcs. A contributing cause of death was most like!y

14. While touring Ihe grounds of the Imperial P"dlacc in Kyoto. a 75-year-old female collapses. She is hyporensivc wilh tachycardia. 111e lemperalure in the shade is 34°C wilh 90% humidily. Aftcr drinking some eool grccn tea, she revives and continues on. The best explanation for Ihesc findings is

O O O O O

15. A previously healthy 52-year-old malc who is a nonsmoker has an episode of hemoplysis wilh coughi.l1g. A chesl radiograph revcals a 6-em ccntral right uppcr lobe mass. A spulum cytology shows alypical squamous cel1s suggeslive of lung cancel. Which of Ihe following inhalct1 pollutams is most likc1y to 1cad lO these tindings?

(A) Rickels (B) Beriberi (C) Scurvy (O) Kwashiorkor (E) Pellagra

11. A basal ccll carcinoma is exciscd from Ihe right lower eyelid of a 72-year-old male. Which of Ihe following

O O O O O

(A) l-Ieal cramps (B) Them1al inhalation injury (C) Heat exhallstion (O) Malignant hyperthermia (E) Heat slroke

O (A) Carbon monoxide O (B) Ozone


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GENERAl PATHOlOGY

o (C)

Radan ga'i O (O) Silica O (E) Carbonaccous dust

16. Incrcascd Ilumbcrs of rcspimtory tract infcction.'i arc obscn'cd among lhe childrcn living in a cornmunity in which rnost familics are al the JXl"cl1y le"e!. lllis finding most likc1y rcsults fmm a dcficiellCY of

O fA) Vitamin E 0(8) Vitamin D O (e) Vitamin K

O (O) Vitamin A O (E) Vitamin B I

For cach of thc c1ínical historic... in qucstions 17 and IR, selCCI thc mosl c1osel)' assoc:ialcd dtllg 01' loxin: (A) Amphelamine (B) Barbi\llrale (Cl Bcnzodiazepine (D) Cocaine (E) Cyanidc (1") Ethanol (G) Gasolinc (H) Heroin (1) Lead arscnate (J) Marijuana (K) Mercuric chloridc (L) Mcthanol (M) Organophosphatc insccticidc (N) Pcnicillin (O) Sulfonamidc 17. A 4-ycar---old cruld ingc.'its a 1000mL hottlc of a c1car liquid found undcr- the kitchcn sink. He dc"c1ops ccntral ncn/DOS systcm (CNS) dcprcssion o"cr thc next fc"" hours. Acidosis is documcntcd on adlllission to thc hospital. Wccks laler, il is noticcd thal lhe ehild's visual acuil)' is markedl)' dL"Cl'eased. ( ) 1H. A 20-year-old stal' football pla)'cl' suddcnly collapses during play and suffers an inunediatc cardi<lc aITCst from which hc cannot be rcsuscitaled. Thc medical examincr is callcd lo invc.'itigalc this suddcn and Ullcx¡x::cled dcath. AUlOPSy revcals markcd coronary alhcrosclcrosis and hislOlogic c"idcncc of hypcrtcnsion in the renal blood "csscls. ( 1 19. A 36-year-old male is the owncr of the radiat(H'" rcpair shop. whcrc he works c1caning. cuuing. polishing, alld wclding mctals. Thc shop is poorly \·cntilatcd. Q\'cr se"cral month.... hc dc"c1ops worscning malaisc witn hcadache. abdominal pains, aud difficult)' holding on to rus lools. A completc blood cell COllnt rc\'eals a micfOC)1ic anemia.. wilh basophilic stippling of red blood cclls on the pcriphcml blood sl1'1e3r. Which of lhe rollowing labarato')' tests wil! suppon the diagnosis uf lcad poisonillg'!

O (A) Elcvalcd hlOOl.l 1c\'c1s uf ALT aOO AST in the sctllm O (B) Elevatcd blood Icvcls of creatinc kinao¡c O (e) Elcvatcd blood levcls of zinc protoporphyrin O (O) Hypcrnatrcmia O (E) Hypocalccmia

20.

Thc child

ShoWIl

berc is most likcly lo have

O (A) Papular dennatosis O (8) Rickets

O (e) I'cllagra O (O) Beriberi O (E) Kwashiorkor 21. A boy fans off his bicyclc while travcling down the strccl at S km/h. Thc skio of his right calf aOO right aon arc scrapcd along the paVCIllCnt so thal tbe top laycr of cpidermis is removed. 1llc best tcnn ror his injury is

O (A) Incision O (B) Conlusion

O (C) Laccmlion O (O) l3ulll O (E) Abrasion 22. Thc rate of dcntal caries 8nd looth absccsscs is high mnollg chiklrcn in an uppcr mi<.kllc c1ass commullity. This pmblclll could be amclioratcd by supplclTlcllting lhe walcr supply with O (A) Zinc

O (B) lodinc O (C) Selenium O (O) F1uoridc O (E) Copper

For each or the c1inical histories in questions 23 and 24. match the mO!>t dosel)' associatcd carcinogcn: Acctaldchydc (B) Ar.;cnic (C) Asbestos (O) Bcnzidinc (E) OlromiulIl (F) Oioxins (G) Naphth)'laminc (H) Nickcl (1) Polycyclic ammatic hydroc:.u·bons

(A)


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(J) Radon ga<; (K) U1traviolct radiation (l.) Vinyl chloride

23. A 72-Ycaf-old ma1c ha<; had incrcasing dyspnca for Ihe pasl ycar. Physical cxamination revcals dcerea<;cd brcalh sounds on auscultating lhe right cheS!. A chesl radiograph demol1.<;lrale.<; a 11Irge pleural ma<;s Ihal neariy encases the righl lung. A pleural biopsy revcals a malignal1l mesothcliOllla. ( )

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ENVlRONMENTAJ. AND NUTRmONAl PATHOlOGY

o (A)

81

Protein

O (B) Vilamin K

O (e) lron O (D) Niacin O (E) Vitamin A

29. A 40-year-old male knows of his family hislory of colon carcinoma. He is concemcd aboul Ihis and want<; lO dclcnninc how besl lO reducc his risk. Which of the following dietary practices should he be adviscd lO follow each day'?

24. A 52-year-old male h~ been a Iifeguard at a beach in California for lhe past 30 ycaN;. Hc has noticcd a nodule on the ouler hclix of his left caro This nodule is now 0.8 cm in diarneler, wilh a central ulccration. It is exciscd and hiSl()logkally dcterrnined lo be a ba.'Wl1 ccll carcinoma ( )

O (A) Orink a glass of red wine O (B) Eat a bowl of ice cream O (C) Reduce inlakc of chocolate O (O) Consume more bcef O (E) Eal more vcgetablcs

For cach of the dinical histories in qucsliolL'; 25 and 26, match Ihc mosl dosely associalcd pollut3nl:

30. Scnding lhe children oul..ide lO play inSlead of ha"ing lbem parkcd for hours in fronl of the lelevision set is mosl helpful in dc"eloping healthy

(A) Asbestos (B) Beryllium (e) Carbon roonoxidc (O) Coal dusl (E) NicOlillc (F) Nitrous oxidc com(XJunds (G) Oxygen (H) 07..0IlC (1) Polycyclic aromalic hydrocarbons

(J) Silica (K) Sulfur dioxide

25. A 6O-ycar-old fcmalc ha<; a 9O--pack pcr )'caf hislory of smoking. Shc has hOO an incn:ascd cough for sevcral monlhs. ln the pa<;1 wcek, she had an episodc of hemoptysiso A chesl radiograph rc"cals a 7-cm, infillrati"c pcrihilar m3S." in lhe right lung. ( ) 26. An oldcr man who 'i"es alone in a poorly ventilalcd house withoul ccntral heating uses a smal! porlable kcrosenc hcatcr lO warm Ihc hOllSC durillg Ihc willlcr monlhs. Hc ¡s found by a neighbor one morning in an obtundcd slate. ( ) 27. A 36--month-old llIa1c appears chronieally ill. Hc ha.. had a succession of rcspiratOl)' infcelions in (he pasl 6 months. TIte child ¡s undcrdcvclopcd. only 50% of ideal body weighl, and exhibits madcd musclc wasting. Laboratory findings indude a normal serum albumin bul a dccrcascd hcmoglobin. Thcsc findings are mosl charactcristic

ro<

o (A) o (B) o (e) o (O) o (E)

Mara..mus Lcukcmia Folale defidcncy Kwashiorkor Bulimia

28. Xcrophthalmia lcad.. lO crosion of a roughened corneal surface in the eycs of a 3-year-old child. ThL.. kerat()malacia rcsults in corncal scarring wilh eventual blindness aflcr several yean¡. Thc ocular damagc could have occn pre"enled by treating a dietary deficicncy of

O (A) Boncs O (B) Eyes O (e) Ski. O (D) lungs O (E) Kidncys

31. A 5-year-old child is admilled lo the hospilal aftcr ingestioll of pills he fOlllld in a cabinet al home. 1be child ¡s rapidly bccoming ob1.undcd and Ihc major laboralory lesl lindings are a serum AST le"el of 850 UIL aOO ALT levd of 1052 UIL. 1ñc child's rc.... piratol)' and cardiac slalUS rcmain stablc. Which of lhe following drugs was probably ingcsted'? O (A) O (B) O (C) O (D) O (E)

AccLaminophen Penicillin Aspirin Sulfamclhoxazole Codcinc

32. A hislory of heart discasc in his mothcr, fathcr, brolher, and Ilncle prompts a 45-yeélr-old male to consult his physician regarding hL.. risk for cOl'Onary artery disea<:e. He ha.. a blood prcs... ure of 125180 mm Hg. He is 17 I cm lall and weigh... 91 kg. His blood glucosc concentrahOIl is 181 mg/dL Whal should bis: physician Icll him regarding his diel? O (A) O (B) O (C) O (O) O (E)

Reduec your intake of saturaled ral. Incrcase your dietary fiber. Takc vitamin A supplemcnl". Do not pul sah on your foo<!. Drink more waler.

33. A 55-year-old ma1c recei"es 4000 cGy in divided doses 10 treal a squamous ceU carcinoma of Ihc larynx. A year later, Ihere is no cvidence of any residual carcinoma. However, which of Ihc followillg hislologic finding... is most likcly to be preselll in this palient?

O (A) Hypocellular bonc marrow O (B) Absent spennatogencsis O (e) Colonic u1ceration


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GENERAl. PAlHOlOGY

o (O)

Va..cular fibrosis O (E) Cercbral atrophy

of a 20-year-old male mal' resull in dcalh throogh which of the following mechanisms?

34. During a qualifying malch for thc World Cup. the goalkCCJXT is hit in the chc.<;t by a football (soccer ball) struck from 10 mclcrs away. He stays in the gamc. Which of the following injury pattcms is mosl likcly lO be sccn o\'cr the chest of Ihc goalkccpcr?

O (B) O (q O (D) O (E)

O (A) O (B) O (C) O (O) O (E)

39. A 5-ycar-old child cxhibits gcnerdli7.cd edema. ascites. and areas of dcsquamating skin ovcr the lrunk and extremilies. The child has had recurrent llppcr rcspiratory infcctiOlls for Ihe past 2 months. Which of the following laborntol)' lindings is mosl likcll' lO be prcsenl in Ihis child?

O (A) Bronchoconstriction

Conlusioll Abrasion Laccration Incision Puncturc

Ccrcbrnl artery thrombosis Heat strokc Gastric hcmormagc Vcmricular fibrillation

35. Ovcr the coursc of 30 minutes. a 19·)'car-old uni"cr~ sit)' studcnl at a fratcmity party drinks 2l of mixcd al~ oohoIic bevcragcs cOlltaining 50% clhanol by "olume. Hc docs: not ordinarily drink much alcohol. His major use of drugs consists of acclaminophcn for hcadachcs. Which of the following complicalions is he mosl likcly 10 expcricncc?

O (A) Hypcrgl)'ccmia O (B) Hypoalbumincmia O (C) Abetalipoprolcincmia O (O) Megaloola..tic ancmia

O (A) O (B) O (C) O (O) O (E)

40. A 48-ycar-old femalc has pain in hcr right wriSl after a fall down a night of slairs. A radiograph uf her right hand and arm revcals marked ostcopcnia. alung wilh a fracture of the radial head. Which of thc following underIying diseascs is lllost likcly to comribllte lO hcr risk for fracture?

Hcpalic cirrhosis AcUle pancrcatitis Suddcn dealh Wcrnickc discasc Ma..si ve hemalcmcsis

For cach of thc c1inical histories in qucstions 36 and 37. malch the mast c1osell' a'iSOCiated nutricllt thal is dcficicllt in lhe dict: (A) (B) (C) (O) (E) (F) (G) (H) (1)

A.scOlbic acid Calcium Auoride Folatc Niacin Pyridoxine Riboftavin Sclcnium Vitamin A (J) Vilamin B l2 (K) Vitamin K (l) Zinc

36. A 42~)'car-old femalc is found lO havc a poslh"C tubcrculin skin test, and hcr Chesl radiograph shows sonlC rigtu uppcr lobc cavitary lesions. SllC is placcd on isoniazid. Howc\·u. aftcr 6 monlh... shc has dcvclopcd a pcriph) eral ncuropathy. ( 37. A 75-ycar~0Id fcmalc ¡¡ves alOl1c and cats sparingly bccausc of hcr low ¡lxcd retircment incomc. She has pain in her legs. A radiograph re"cals a right tibial subpcriosteal hematoma. A cut on hcr right hand is hcaling poorly. Shc has a hypcrkeratotic ra... h. ( ) 38. Contact with a fraycd c1ct:trical eord carrying 120\'olt. Io-ampcre allcmating current Ihrough the right hand

O (E) H)'JXlCalcemia

O (A) Coronal)' alherosclerosis O (B) Pulmonary cmphl'scma O (q Primary biliary cirrhosis O (D) Chronic Iymphocytic Icukcmia

O (E) Atrophic ga..trilis 41. A 61-ycar-()ld male with a histo!)' of ehronic arthritis complains of pronoullccd tinnitus, He also has somc diui· nc...s. with headaehc. Physical cxaminalion TC"cals somc scaucrcd ¡X::lct:hiae ovcr the uppcl' cxtremitics. A stoo] gUlliac tcst rcsuh is posili"e. Which of the following drllg toxicities best explains Ihese lindings?

O (A) Pellicillin O (B) TelCac)'c1inc O (C) Aspirin O (O) OtIOf'promazine O (E) Quinidinc 42. A 26-ycar-()ld kmalc has had amenorrhca for the pa.. t 8 )'cars.. Shc incurs a right wrisl fracture artcr a minor fall to thc ground whilc gctting oot of an automobilc., and shc is found lO have dccrcascd bonc density on performancc of a radiograpruc dcnsitolTlctl)', LaboC'alory findings inc]udc anemia and hypoalburnincmia. The underll'ing eondition that best explains these findings is

O (A) Kwashiorkor O (B) Obcsity O (q Anorexia ncfVosa O (O) Scurvy O (E) Rickcts


Chopter 9

43.

llle mosl common wortdwide dietary deficiency is

o (A)

!ron

O (B) O (e) O (O) O (E)

Calcium Folalc Vitamin C Chocolale

44. The liremen who inilially responded to lighl lhe fires from the Chernobyl rluclc<'lr reaclor aceidcm wcrc cxposcd lo high mdiatioll 1cvels. Sorne of Ihem had dosages excccding 5000 cGy. Wilhin hOUTh. mey dicd from severe d3mage lO

O (A) Bone marrow O (B) Ccrebrum O (e) Small inlcslinc O

(O) f1=t

O (E) Lungs

45. Thcre are no extcrnal findings 011 examillalion of lhe body of a 30-year-old femalc found in hcr hotel room an hour aner firemcn eXlillguish a firc 011 Ihe ([oor oclow. Which of lhe following injuries besl explains her death'l

O (A) PsetulolllOlws O (B) O (C) O (O) O (E)

lJel'lIgillo.m septicemia

lnhalatioll injul)' Acule myocardial infarction Cerebral edema Malignanl h)'pcnhennia

46. Chronic alcoholics are at incrca.scd risk for which of Ihe following di.'>Of"dcTh?

O (A) Blilldncss O (B) O (Q O (D) O (E)

ENVlRQl\JMENTAl ANO NUTRmONAl PATHOLOGY

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83

cry. An ultra'iiound scan re"calcd a largc retroplaccnlal llemonhage. Dclivcry was accompanicd by a 12(X)..mL bl00d ,"". ( )

48. A 22-ycar-old male is brought to lhe hospilal cmcrgency dcpartmcnl in a stalc of rcspiratory dcprcssiOl1. Hc cxhibilS convulsiOlls for sc\'eral minutes befare a cardiac arresl cnsues. Advanccd cardiac Jife support mca~ures are institutcd. and he is stabilized and intubatcd. Whilc pcrforming a physical cxaminatiol1. Ihc physician notices Ihat he has nccdle tracks in thc Icft al1lecubita\ fossa. He also has a temperalurc of 39.2"C. A loud dia~lolic hcart murmur is audible. ( ) For each of Ihe dinical histories wilh accompanying picturcs in question... 49 and 50. malch the ITIOSt c10sely a'>SOCiated environmcnlal insull or nutritionaJ disca'iiC SlalC lhal may be seco inyolving thc skin on physical examinalion: (A) (B) (C) (O)

(E) (F)

(G) (H)

Abrasion Blast injury Contusion EleclrocllliOIl injury GUllshot W0l1l1d Hypothermia lncision Kwashiorkor Laecration Pcllagra

(O (J) (K) Se",,,)' (L) Sunbum

(M) Thcrapculic radiation (N) Thcnnal hum (O) Vilamin A 10xicilY (P) Zinc dcficiellcy

Carcinoma of Ihc esophagus Carcinoma of lile stomach Peripheral vascular discase Acule renal failul'e

For cach of t:hc c1inical histories in qocstions 47 and 48, malch the masl dosely as.sociated drug: (A) ACClaminophen (B) Ampbelaminc (e) Cannabinoids (O) Cocainc (E) Ethanol (F) I-'urazcpam (G) Heroin (H) Lyscrgic acid (1) Mepcridille (J) Phencyclidine (K) Phellobarbital (L) Propoxyphelle 47. A fClus was slillborn at 36 wceb' gc."lational agc lo a 23-}'car-(lld female. 1bc molhcr cxpcrienccd the sudden ollSCI of lower abdominal pain sc\'eral hours before deliv-

Counesy of Georgc

K:usa.~.

MD. r"'Orensic palhologisl, Boslon.

49. A l4-year-old bay was taken to t.hc emcrgcncy departmcnl of a local hospital, whcre he dicd scvcral hours later. His hematocrit \'las 17%. Figure shows a piCIUTC laken al aulopsy ( )


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GENERAL PATHOLOGY

4. (B) Although hcpatic adcnomas arc rare tumors. therc is a well-dcl"ined associalioll bclwccn these bcnign liver lumors and prolonged oral eontraceptive use. 111ey ean regrcss after eessation of thc medication. Thcre is no increa<¡c in thc ri.<;k of endomctrial canecr bccausc the presencc of prugestins in oral conlraccptivcs prolccls againsl Ihc cffect of estrogcns. 'nle incidence of ovarian cancer is actually lower in Ihose who usc Ihe pill. BP623\ PBD64\4-416 5. (1) Iron deficicncy givcs rise 10 mierocytic anemia. It is common in women of reproductive age, bccause of mcnstrual blood loss. and in children with a poor dic!. prcgnant womcn have grcally incrcased iron nccds. Serum fcrrilin is low in iron dcficiency BP6 258 PBD6 452 f'rQm the leaching oollection of the Dcpanmcnl or r3Iholog)', Soulhwcstcrn ML'iJic:ll SchooL Dalias, TX

50. A 5-year-old boy is scnt lo be cxamined by a physician. This picture was recorded by the physician. A poliee agcncy SuspcclS possible child ;:¡busc. ( )

ANSWERS l. (D) She is morbidly obcse. The extra weight puts strdin on joints, particularly on lhe knees. 'Thc rdaLion belween cndOlTIelrial carcinoma and obesilY is wdl eSlablishcd. Aboul 80% of pcrsons with typc LI diabetes mellilus are obesc. There is no associalion wilh pulmonat)' emphysema. BP6259-261 PBD6452-45<1 2. (B) This palienl devc10pcd dccompression sickness on relurn fmm diving in the ocean. TDo rapid an m¡Cenl results in dissolved nitrogen gas eoming out of Ihe blood lo fonn bubbles lhal cause symptOlTIs from occlusion of small artcries and arterioles. This process is called tite bel/lis. Hypolhennia does not have significant symploms or lissuc crfccts. Oxygcn IOxicilY causes pulmonar), diffusc alveolm' damagc-a process thal lypically complicates inlubation and mcchanical venlilalion in hospilalized palienls. A blast injUlY may pnx\ucc conlusions. but the waler pressure at 50 melers is not grcal enough to do Ihis. 1l1C symploffio; he has are nOl characlcristic for hypoxemia. PBD6436 3. (n) Alcoholics are oflcn ddicicnl in thiamine and olher lIulrienls (cthanol provides "cmplY caloncs"). 111iaminc deticiency can 1cad lo ncuropathy. cardiomyoparhy. and Wemicke disease. Alcoholics often have folale deficicncy wilh macrocytic ancmia. Pyridoxinc or ribonavin deficicncy can lead lo ncumpalhy but not cerebral findings. Niacin dcliciency leads lo pellagra. BP625<1-255 PBD6447

6. (.1) Pcllagra is causcd by a deficiency of niacin. The c1assic prcscnlalion includes thc "3 Os" of diarrhea, dennatilis, and dementia. BP6255-256 PBD644B 7. (E) ÜX:lline is a powenul vasoconstrictor and has a varicly of vascular cffccts. Many cOlTlplicalions result fmm the cardjova..cular cffccls thal indudc artcrial vasocotlstricliDn with ischemic injury and arrhythmias. I-Iypcrthenuia is another cOlTlplication. Acute ethanolisrn may 1ci.1l! 10 CNS deprcssion but nol scrious illll11cdiale cardiac cffcels. Heroin may pmduee acutc puhnonary edema. Marijuana has no serious acule lOxicities. Phencyc1idine (Pe!') producc.<; an acule loxicily Ihal mimies psychosis. BP6236 PBD6412-413

8. (D) Aeclaminophcn toxicily lcads lO hepalic nccrosis. and Ihe ALT and AST levds arc c1cvalcd. If dcalh is nol ilTImOOiate. hypcrbilirubincmia can also be secn. Hypoka1c~ mia can be a fcalurc of renal disca<;c!'> and of glucocorticoid deficiency. The scmm crealine kinllSC leve! is c1eVi.IICd wilh injury to skelctal <Ind c;.udi¡¡c musclc. KClOnuria is a fei.llure of absolule in!'>ulin deficicncy wilh diabclc... mc1litus; it is also a fCi.llure of starvalion. Thc SClUm amyla..e is devated wilh panercalitis. BP6231 PBD6416 9. (O) Coagulalioll factors sYlllhesized by the livcr rcquirc vitamin K for lheir production. Hcmonhagic disease of Ihe newborn can oceur becausc endogenous pnxluction of vitamin K is limitcd in nconatcs. This results rmm mini mal cstablishmcnl of the intcstinal baclcrial nora Ihal produce Ihis Ilutricllt. lron dcficiency Icads lo anemia. nol 10 blccding. Vitamin E is an antioxidant and is rarcly deficient to a degrce Ieading lo scrious illncss. Folic acid hclps lo prevcnt a macrocYlic anemia. lodine is necded in SlTIall quantities fol" Ihyroid hormonc sylllhesis. BP6253-25<1 PBD6446-447

10. (e) Because humans do nol genernle vilamin C cndogenously. lhey must havc a continuous dielary supply. TIIC lack. of frcsh fmits and vcgelables wilh vitamin C loo 10 seurvy in many cxplorcrs in centuries pas!. Rickcts is scen in ehildren deficicnl in vitamin D. Beriberi lcads lo heart failure and rcsuhs fmm Ihiamine dcficicney. Kwashi-


<

"ot [oc ..ale! ~

<

Ke

.nn.

n¡X>,ll,a><M ! ~

Olopfer 9

orkor results from protein dcliciency. Pcllagra (with diarmea, dennatitis. an<! delllentia) is scen wilh niacin deficiency.

BP6256-257 PBDó 449-451 11. (A) Exposurc lO sunlighl is a risk for malignancics involving lhe skin (Le.• basal ccll carcinoma. squamous cell carcinoma. and malignanl melanoma). 'The ullf3violel rays. mainly lhe UVB componelll of UV lighl, are Ihe major callsativc agenl for Ihesc malignancies. Infrarcd radiation causes rnainly thcnnal injury. Visible lighl has mini mal effecls. The ambielll x-rddiation and gamma rays lhal filler Ihrou&h Ihe earth's atmospherc are very small in quanlilY.

BP6711

PBDó 430-431

12. (E) Old flaking painl lhat is lead ba.<;e<1 has a sweel laste. atlracting childrcn lo ingcsl it. The major risk lO childrcn from lead ingc.<;tion is neurologic damage. HOlIsehold bleach (sodium hypochlorite) is a local irritanl and is not likcly 10 be foond in Ihe living coodit.ion.<; of these children. Ethylene glycol is found in anlifrcc7.c and can produce acule renal lubular necrosis. Mcthanol ingestioll can cause acule CNS depres...ioll. acidosis. and blindness. Ker~ne, a hydrocarbon. can cause gaslroinl~tinal and rcspiralory 10xieilY when ingested.

BP6231-233 PBD6420-422 13. (A) Cocaine. as a powerful vasocollslncllve agenl, causes ischemic injury lo the na.<;al scplum following Ihe roule of ac:!ministration-inhalalion. CNS hernorrhagcs may occur as an aculc eomplication. 1llc eaJlus comes from f1icking Ihe lighlcr for lhe crack cocaine pipe. Opíalcs can be CNS and respiratory dcpres.sant.~ Cannabinoids in marijuana do not generally eause serious acule problcms. Amphelamines are CNS stimulants. Barbiturales are CNS dcprcssant....

BP6236-237 PBD6412-413 14. (C) Heal cxhauslioll rcsults fmm lhe failure of Ihe cardiovascular syslem 10 eompcnsale for hypovolemia cause<! by water deplctioll. It is rcadily reversible by Teplacing losl inlravascular volume. Vigorous cxercise wilh c1octrolylc los." can produce muscJc cramping Iypieal of heal cramps. InhalatiOIl illjury is scen whcn a fire occurs in an enclosed space. and hol, toxie gases are inhaloo. Maligllalll hyperthcrmia occurs from a mclabolic dcrangemcm such as thyroid slorro or wilh drugs sucll as succinyl cheline.

BP6240 PBDó 434-435 15. (C) lbcre is a nalural seepage of radon ga... fmm wil. more so in sorne gcographic localions Ihan olOCrs. This gas can collect in houses aOO is a polentíal cause ror Illng canceL The pollutant ga-.cs carbon ITlOnoxide and ozonc are nol associalcd with lung cancer, Ilor are dusls containing carbon such as eoal dusl. Silicosis may possibly increasc Ihe risk for lung canccr. bul Ihcre is severe rcstriclive lung discase wilh silicosis.

BP6242-243 PBD6418 16. (D) Vitamin A i... imponanl in maintaining cpilhelial surfaccs, an<! a deficiency can lead lO squalllOllS mctaplasia

ENVlRONMENTAL AND NUTRI110NAl PATHOlOGY

85

of rcspiratOl)' epilhclium. predisposing lO infcctioo. Vitamin E de6ciency is r.uc. aOO when prc.<oelll, il causes ncurologic symptoms rclalcd lO degenerntion of the axon... in lhe posterior column... of lhe spinal cord. Vitamin O deliciene)' in childrcn lead... lo Ticket..... with bolle deformitics. Vilamin K deliciency can rcsuh in a blecding diadlC...is. Vilamin B. (Ihiamine) deficicncy Icads lO a varielY of problems incJuding Wemickc disease. neuropalhy. and cardiomyopathy.

BP6246-248 PBD6439-441 17. (I~) Melhanol is metabolizcd by Ihe smne em:.ymatic pathway a... ethanol, but Ihe LOxic metabolilcs formaldehyde and acctaldch)'de are produced. which damage the CNS and the retina.

BP6232

PBDó 412

18. (O) Cocaine is a powerful vasoconslrietor. and the eardiac complicalions include arterial va.'iOCOIl.<;lriction wilh ischemic injury aOO arrhYlhmias. Alhcrosclerosis. af· feding small pcriphcra.l coronary arterial branches, can be marlcro.

BP6236-237 PBD6412-413 19. (e) This person has expericnced occupational exposure lO lead and shows ~ymptoms and sign~ of lead loxicity. 1ñe conccntration of zinc proloporphyrin is c1evaled in chronic lcad poisoning, in anemia of chronic disease. alld in iron deficiency anemia. Lcad imerfercs with heme biDsynthcsis and inhibil" lhe illCOf"lXI3tion of iron into heme so lbal rinc is uscd inSlead. Hepatic damagc with eJevation of liver enzymes ALT and AST is 001 a major feature of Icad poisoning. Thc Icvel of the muscle enzyme creatine kina..e is 1101 elevalcd bccause musde is not directly damagcd by lead. ahhough a ncuropathy can occur. l..cad can damage renal tubulcs and cause renal failure. but spccilic alteration~ in c1cclrolYles WÍth c1evated l;()(lium or decrcascd calcium me nOl spccific for lead·induced renal failure.

BP6232-233 PBD6420-422 20.

(8) This ~kclclal dcfonnily with bowing of the legs

resull~

fmm vilamin O dcficicncy in childrell, known as ricket.... Hyperkeralosis with foJ1icular plugging fmm vilamin A deficiency leads lO papular dennalosis marked by cxteosivc papular excrescences 00 lhe skin. Pcllagrn fmm niacin dcficiency can Icad to dcnnatitis in sun--exposcd atea... of skin. Beriberi fmm lhiamine deficicTIC)' can resulI in hcart failuTC wilh pcripheral edema. A diel poor in protein can resull in kwashiorkor. with arcas of f1aking, depigmcmed skin.

BP6249-25O PBD6444-445 21. (E) A scraping injury produces 3rt abrasion. but the skin is nol broken. An inciscd wound is made wilh a ~harp instrUlnclll such a.. a lmife, Jeaving c1ean edges. A contu· sion is a bruise with exlravasatioll of blood inlo sof! tis· sucs. Lacerations break the skin or othcr organs in un irregular fa~hion. A bum injury causes coagulalive l1CCTOSis wilhoUl mcchanical disruption.

BP6 238 PBDó 432


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GENERAL PATHOLOGY

22. (O) Waler in some places naturally contains fluOlide, aml denlal problems in children are fewer in Ihese places. Fluoride can be put in the clrinking water, but opposilion from ignorance or fear is common. Zinc deficiency can produce a hemorrhagic dermalitis. lodine deficiency can predispose to goiter. Selenium deficiency can result in a myopathy. Copper deficiency can produce neurologic defects. Serious i1\nesses from Irace elemenl deficiencies are rare. BP6 258 PBD6 452 23. (C) Asbeslos fibers can cause pulmonary interslitial fibrosis, and there is an increased risk for malignancy. Persons who have had asbestos exposure and who are smokers have a greatly increased incidence of bronchogenic carcinoma. Mesolheliollla is unCOlllmon, even in persons wilh asbestos exposure. but virlua1\y all occurences are in persons who have been exposed lo asbeslos. BP6227-229 PBD6732-733 24. (K) The UVA and UVB ponions of the llltraviolct spectrum conlribute lO an increased incidcnce of skin cancer in pcrsons wilh chronic sunlighl exposure. PBD6430-431 25. (1) llle infiltralive pelihilar rna"s suggests lung cancer. Polycyclic hydrocarbons and nitrosamines. found in tobacco smoke. are the key conlributors lo Ihe developrnenl of lung cancer. BP6223 PBD6 408-409 26. (C) Heating devices Ihal bum hydrocarbons such as petroleulll prodllCtS generate carlxm dioxide. which can build up to dangerous levels in unvenlilaled or ¡x){)rly ventilalOO houses. Chronic carron monoxide poisoning pnr duces CNS damage. The carbon monoxide binds much more lighlly lo hemoglobin than does oxygen and leads lo hypoxia. Decreased mental fUllctioning generally begins at carboxyhemoglobin levels grealer Ihan 20%, with dealh like1y arove 60%. BP6234 PBD641B 27. (A) Body weighl less than 60% of normal wilh musele wastlng is consislenl wilh marasmus. which results from a marked decrease in total caloric imake. In kwashiorkor. protein imake is reduced more Ihan tOlal calaric intake, and body weighl is usually 6lf1b to 80% of normal. wilh hypoalbuminemia a key lalx)ralory finding. Malignancies can prumote wasting. bUl nol to Ihis degree. This child's problems are far more serious Ihen a single vilamin deficiency: a lack of folate could accoum for Ihe child's anemia. but nol wasling. Bulimia is an eating disorder of adoleseems and adults lhat is characterizOO by binge eating alld self-induced vomiting. BP6244-245 PBD6437-439 28. (E) Vilamin A is essential to mainlain epilhelia. The lack of vitamin A affecls Ihe funclion of lacrimal glands alld conjunctival cpithelillm, promoling keralomalacia. I)ielary prutein is essenlial for building tissues, panicularly muscle, but il has no specific effecl in maintaining ocular stmclures. Vilamin K is beneficial for synthesis of coagulatioll factors by the liver to prevent blccding problcms. lron

is essential for produclion of heme to manufaclure hemoglobin used in making red blood cells. Niacin deficiency leads lo dialThea. dermatilis, and dementia. BP6248 PBD6439-441 (E) More fruits and vegelables are recommended in Ihe diet lO help prevenl colon cancer. Vilamins C and E have an anlioxidant and antimutagenic effecl. Red wine in moderalion may have a beneficial anlialherogenic effecl. Ice cream can include animal fal Ihat may promole cal'lCer. as would the animal fal af beef. BP6261-262 PBD6455-456 29.

30. (A) Vitamin O can be synthesized endogenously in skin wilh exposure lo ultraviolel lighl. Vitamin O wilh ca1cium helps to build growing rone. The exercise helps build rone mass. Given Ihe increases in air polllllion in many cities, pulmonary diseases are increasing, with children being al risk. Renal function is nol greally affected by environmenl. BP624B PBD6442-445 31. (A) Acetaminophen loxicity produces hcpalic necrosis. This effecl is enhanced wilh prior ethanol ingeslion. Hepalic necrosis is indicatOO by cXlremely high levels of AST and ALT. Penicil1in may cause systemic anaphylaxis in a few persons. Aspirin can produce a melabolic acidosis. Sulfa drugs may produce renal failure. Opiales. including codeine. are CNS and respiratory depressanls. BP6230 PBD6416 32. (A) These findings suggest a diagno!>is of diabetes mellilus. He is also obese and mosl likely has type 11 diabetes. Type I and Iype " diabeles greatly increase Ihe risk for early and acceleraled atheroselerosis. Decreasing lolal caloric intake, particularly saturatOO fal. helps reduce Ihe risk for cOfOnary artery disease. Vegelable and fish oils are beuer Ihan animal fal in lerms of dietary lipid for prevemion of alheroselerosis. Dielary fiber helps lo reduce the incidence of diverticulosis. Vitamin A has no known effect on alherogenesis. Reducing dielary sodium helps lO lower blood pressure. More fluid inlake aids renal fllnction. BP6 261 PBD6 452 -454 33. (O) Therapeutic doses of radiation can cause acule vascular injury. manifeslOO by endolhelial damage and an inflammatory reaction. With time. Ihese vessels undergo fibrosis and suffer severe luminal narrowing. There is ischemia of Ihe summllding lissue and fonnation of a seaL 'Ihe radiation used in IherapeUlic dosages is carefully deliv· ered in a limiled field lO promole maximal lumor damage while reducing damage lO sunoundillg tissues. Whole-body irradiatian affects marrow. gonads. gaslrointestinal trael, and brain. BP6 242 - 243 PBD6 42B 34. (A) A blow wilh a blum objecl produces soft lissue hemorrhage wilhoul breaking the skin. An abrasion scrapes away lhe superficial epidermis. A laceration is an irregular lear in Ihe skin or other organ. An incised wound is made by a sharp object and is langer Ihan a pllnclUre, which has a rollllded outline and is deeper than il is wide. BP6 23B PBD6 432 -434


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35. (C) lñe large amoulll of ethanol ingested over a shor1 lime can devate his blood etllanol to loxic le,'els, becalL<;e lhe aloohol dehydrogenase in liver metabolizes ethaool by first-order kinelics. Cirrhosis is a Iong-terrn complicalion of chronic ethanolism. Likewise, pancreatitis is also a fealure of chronic lL..e of ethallO!. Wemicke dis-ease is rMe. even in alcoholics, and probably occurs from llutritional thiamine deficierlCY. Hematemesis from g3!>1ritis aOO gaslric ulceratioll are more Iypically seen wilh chronic elhanolism, and variceal bleedillg is a complication of hepalic cirrhosis. The combinalion of acelaminophen and elhanol increases the likelihood of hepalic toxicily.

BP6234-235 PBD641O-412 36. (F) lsoniazid ONH) is a pyridoxine anlagonisl. Per· sons on lNH lhempy for luberculosis may need vitamin 8(, supplementation.

BP6 256 PllD6 449

ENVIRONMENTAl AND Nt.JTRlTlON.A.l PATHOlOGV

87

Tetr.tc)'c1ine lher.tpy may be complicaled by a falty liver. Chlorpromazine ingestion may lead to choleslatic jauOOice. Quinidine ther.tpy may lead lO hemolytic anemia.

BP6231-232 PllD6 416 42. (e) 1be decreased food intake from self-imposed dieting in an aduh femOlle can lead to changes such as hormonal deficiencies (e.g., follicle-stimulaling hormone, luteinizing hormone, Ihyroxine). The result is diminished estrogen synlhesis. which promoles osleopol'Osis jusI a., in Ihe poslmellopausal slale. Kwashiorkor is a disease mainly of children who have reduced prolein intake. Obesily can be accompanied by sllecific nutritional deficiencies. even thougb tolal caloric intake is increased. bUI hypogonadism is nol a typical feature. Scurvy fmm vilamin C deficiellCY does 1101 affect hormonal function. Rickels is a specific deñcieney of vilamin J) in children resulting in sketelal defonnilies.

BP6 246 PBD6 439 37. (A) Scurvy can be subUe. A diel must contain a con.'.lanl supply of vitamin C, because none is made endogenoosly. Older petSOflS wilh a poor diet are just as much at risk as younger persons.

BP6256-257 PBD6449-451 38. (E) Eleclrical currelll, especially alternating currenl, disruplS nerve conduclion alld e1eclrical impulses, particularly in heart alKl brain. This can lead to severe arrhythmias, especially ventricular fibrillation. lñese are immediate effects. The amount of tissue injury from standard (U.S.) household current is generally 1101 g.real. aOO lhere may be jusI a small thermal injury al the site of entry or exit of the current on the skin.

BP6 240 PBD6 435 39. (8) 1be findings are consistenl with kwashiorkor, a nulrilional disorder predonllnantly of decreased protein in the die!. Hypoalbumenia is characleristic of this condition. The w~1ing of diabeles mellilus affects adipose tissue and muscJe, Olnd edema is nOI a feature. Abetalipoproteinemia is a rare disorder leading 10 vitOlmin E deficiency. Megaloblaslic anemia is a feature of specific deficiencies of vitamin B12 or folate. Hypocalcemia can occur as a COIISequence of vitamin D deficiency.

BP6244-245 PBD6437-439 40. (C) 1ñe osreopenia can resuh from osteomalacia, the adult forrn of vitamin D deficiency. Vitamin O is one of the fal-soluble vitamins. aOO il requires fal absorption. which can be impaired by chronic choleslatic liver disease, biliary trdCI disease, aOO pallCre<ttiC disease. Hean disease from atherosclerosis does nol affect bone density. Emphy. serna can result in a hypertrophic osteoarthropalhy, but nol osteopeniOl. Leukemias do n(l( lend to erode bone. Atrophic ga...tritis affects vitamin B12 absorplioll.

BP6251

PBD6444-445

41. (C) Chronic aSIJirin loxicity (more than 3 g/day) can result in a variety of neurologic problems. Aspiri.n also inhibits platelel function by suppressing the produetion of thromboxane Al' promoting bleeding. 1be best known complication of penicillin lher.tpy is systemic anaphylaxis.

43. (E) lbere is never quile enough chocolate. and much of lhe world's populmion has lO gel by wilhoul il. Of C()llrse, serious dietitians would choose answer A. which is a deficiency mosl likely to be seen in menslruating women, in pregnant women. and in children. Ca1cillm is masl importanl in growing children for building bones. Folate deficiency leads lO macrocYlic anemia and is mosl likely to occur in adults wilh a poor dieto such as persons wilh chronic alcoholismo Vilamin C deficiency occurs in persons who do nol. get enough fresh fruiL<; and vegetables.

BP6 258 PBD6 452 44. (8) 1be cerebral sYlldrome occurs within hours with a massi\'e lotal-body radiation dose. Oealh can occur with dosages froro 200 to 700 cGy bul takes days to weeks from injury lO radiosensitive marrow and ga<;U"()Íllteslinal tracL Muscle tissue is relath'ely radioresislanl. Early findings wilh radiation lung injury include edema, and interstilial fibl'Osis develops over years if survival occurs.

BP6 243 PBD6426-427 45. (8) Fires in enclosed spaces produce hOl, loxic gases. The inhalation of lbese gases can leOld 10 dealh wilhoul any injury froro ftames. Infeclions follow a bum injury by days lO weeks hec-.tuse of the loss of an epilhelial barrier lo infecfious agents. An acule myocardial infarction is possible bol not probable at her age. Cerebral edema is a complicatioll more likely during recovery from a bum injury. 1be condition of malignant hyperthermia, when rore body temper.tture exceeds «fe. is produced by m::tabolic disorders such as hyperthyroidism and drugs such as succinylcholine and cocaine.

BP6 239 PBD6 434 46. (8) Alcohol inclllases Ihe risk of callcer in Ihe upper aerodigestive tracl, including the moulh. pharynx, and esophagus. In the slom.\Ch. it can cause acule and chronic gastritis, but Ihere is no reported increase in gastric cancer. Peripheral vascular disea<;e is usually cause<! by atherosclerosis. Alcohol does l10t increase atherosclerotic di...ease ill~ cidence. 81indness is an acule toxic effect of methano1


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GENERAl PATHQlCX;Y

ingesúon. Acute renal failure results from ingesliOll of ethylene glycol. BP6234-235 PBD6412

diac arresto 11le Iypica\ mude of adminislralion is by injec· tion, and there is ofien an ¡nfeclion. sueh as an endocardilis., thal results from such use. BP6237 PBDó 414

47.

(1» Cocaille has powerful vasoaclive effecls. illcludjllg vasocollslriclioll. The effecls 011 the placenla can in· c1ude decreased blood flow wilh felal hypoxia and spolltaneous aoortion. placelllae abruplioll. and fetal hemorrhages. Wilh chronic malernal cocaine use. lhe babies demonslrale neurologic impainnenl. BP6236-237 PBDó412-413

48. (G) Heroin is an opiale narcoüc Ihal is a derivalive of morphine. Opiales are CNS depressanls. Overdoses are accompanied by respiralory depression. coll\'ulsions. and cal'-

49. (E) This js Ihe entry site fOf a gunshol woulld made from c10se range. 111ere is a sh.arply dem.arcated skill defect., and lhe surrounding skin demonslrclles sorne stippling

of unbumed gunpowder. BP6 23B PBDó 433 50. (A) Tbere are superficial lears in Ihe epidermis. with underlying superficial dennal hell1OIThage. Abrasions are made by a sCl'apjng type of injury. BP6 23B PBD6 432


CHAPTER

10 Diseases of Infancy and Childhood BP6 Chapter 7 - Genetic and Pedlatric Dlseases PBD6 Chapter 11 - Diseases of Infancy and Childhood

l. A baby bom al 10m weighs 19UU g. "Ibe head size is normal. but lhe crown-heel length and foot length are re· duced. No exlernal malfonnations are observed. Through ¡ufane)'. developmemal miles:IOnes are delayed. 1be most likel)' condilion occurring during gestalían lhal could It"ad to lhese findings is

O CA) Pregnancy-induced hypenensioll O (8) Down syndrome O (C) Maternal diabetes mellitus

O (D) CongenilaJ cytomegalovirus O (E) El)'throblaslosis fetalis 2.

support. He seems to improve for the firsl 24 hours bUI lhen recomes progressively more cyanotic. He develops terminal seizures and dies 4 days after binh. 1lle mosl likely histologic finding in lhe lungs would be O (A) Diffuse alveolar seplal fibrosis O (8) Alveolar hyaline membranes and atelectasis O <O Extensive alveolar transudale O (O) Bronchiolar mucus plugging O (E) A frothy (bubbly) alveolar exudate 4. Steatormea as a consequellce of pancreatic acinar atrophy wilh fibrosis is mast likely 10 be seen in a child with

O (A) Galactose-I-phosphale uridyl transferase deficiency O (B) A low«nsity lipoprotein (LDL) receptor gene mutation O (C) Abnonnal fibrillin production by fibroblasls O (D) Impaired epithelial cell chloride ion lransport O (E) Phenylalanine hydroxylase deficiency

An IS-monlh-old. apparelltly healthy ¡\frican-American

boy is found lIead in his crib Dile Illorning. "ñe lerrified and distrallghl parents, both blue-collar wOl'kers. are iulerviewed by !.he medica! examiner and indicale Ihat lhe child was nOI ¡!l. The medical examiner finds no gross or microscopic abnonnalilies at autopsy, and all loxicologic lesls are negalive. nle medical examiner tells lhe parenlS Ihat, ahhough she cann04. find Ihe cause of death, she feels lhal SUddell infant dealh syoorome fSIDS) is very unlikely. This conclusioll by lhe medical examiner is based on which of the following faclors:

O (A) $ex of the child O (B) Race of the child

O (C) Age of the child O (O) Low socioeconorrlic background of parenlS O (E) Absence of any aboonnalily in lhe respiralory centen>

3. A premalllre male newborn delivered after 28 weeks' gestation develops difficllllY in brealhing 2 days afler binh. A chest radiograph Teveals a bilateral ground+glass appearance. He is treated with assisted ,'entilation and nutritional

5. An infanl is found to have a palpable abdominal mass, along with fever and weighl loss. An alxlominal sean reveals a 5.5-cm mass involving lile righl adrenal gland. A 24·hour urine homovallillic acid (IIVA) is increased. 'Ibis adrenal is surgically excised, and the histologic appearance

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GENERAL PATHOlOGY

of lhe mass is shown in lhe figure. Which of the following c1inical or hislologic fealures of this Icsion is associated wilh a poor prognosis?

rcsuscitalive measUfCS. Microscopic examinalion of lhe bab>"s lungs al autopsy is shown in lhe figure. Which of lhe following condilions besl accounrs for thcse findin!!s?

a (A) a (E) a (e) a (D) a (E)

a (A) Maternal IOxemia of pregnancy a (8) Marked fetal aocmia a (e) Congenilal foxoplasmosis a (O) Immatllrily uf Ihe lungs a (E) Oligohydramnios

Age younger than I year Hyperdiploidy Presence of mallY ganglion celts N-myc gene amplificatiotl Malform~tions of the kidney

8. Soon after birth. a 4O-week-gcslalional-age baby has a hean murmur audible on auscultalioll of lhe ches!. On echocardlography thcre is a rnembraoous ventricular septal defccl (VSD). Which of the fol1owing evenls is mosl likely fO have resulled in Ihe appearance of this VSD?

a (A) a (8) a (C)

Oispenny al concep60n Malernal fhalidomide use Maternal rubella infectioll O (O) Erythmblaslosis fetalis O (E) R>13Ic dcficicncy 9. ',be amoul1l of :<urfaclam in Ihe developing lung increases bctwecn tht> 261h and 32nd weels of gestalion. This increase is relaled lO which of lhe following developmemal events?

a (A) a (H) o (C) 6.

A cesarean section musl be performed al 27 week-s because of lhe lesioo shown in the figure. Tñe :!8+year-old molher began lO ha\'e prelerm labor. 'llle depicled Icsion is mast likely lO be a

O (A) Tenlloma (8) Neuroblastoma

a a (C) a (1) a (E)

I-Icmangioma Lymphangioma Hamartoma

Difíeremiarion of aJ"eoli from cmbryonic foregul Increased dCllsify of pulmonary capillaries Developmenl of ciliated epifhelil1ll1 in airspaces O (D) Differentia!ion of type 11 alveolar epithelial cel1s O (E) Apoplosis in intcrlobuJar mesenchymal cells 10. A 22-year-old primigravida delivers a 38-week-geslalional-age maJe baby lhar aprears nonnal on physical examinarion, excepl for a single midline clef1 of the upper lip. lrus cien lip inleneres with breasl-feeding, ahhoogh the baby gains weighl nomlally. The 1l10ther asks yoo if there is any risk Ihal her othcr children will be born wilh a similar malfonnafion. You give the foltowing advicc:

O (A) It is highly unlikely tha! other offspring will have a similar defecl. 0(8) There is a small bUI definire risk. in lhe range of

291: to 7%. lhat her olher chiklren wiH have a c1eft lip.

O (C) It is Iikely that one half of her ofíspring will ha\'e cleft lip. risk of having olher children with a similar defcct is one in four. O (E) Her sons bul not daughtcrs are al risk fOl" clefl lip.

a (O) 'Iñe

11. A 20-year-old female is plallning for her tirst pregnancy. aOO shc is adviscd by hcr physician fhal she musl begin a phenylalanine-free dict before conccption alld must conlinuc wilh lhis diet Ihmughoul aH three lrimcslCrs of her pregnancy. OtheTwise. her baby could be afTceted by

7. A 31-week-gestational-age neooale has initia! Apgar scores of 5 and 6 at I aOO 5 minules; bul wilhin an hour, the baby is in severe respirafory disfress and dies despile

a (A) Mental ret:anlation a (8) Muscular weakness a (C) Cataracts a (D) AIK:rnia O (E) Congcstive hearl failure


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12. Which of the following factor.> is mosl like1y to in· crease lhe risk fOl" neonalal hyaline membrane disease in a 34-week-gestational+Olge baby?

O (A) Maternal cortiCOSleroid ther.l.py O (8) Olorioamnionitis O (C) Gestational diabetes O (O) Oligohydramnios

DlSEASES OF INFAf\lCY MlD CHllDHOOD

91

lhese finc:tings, which of lhe following e\'ems is mosl likely lO occur?

O (A) Kernicterus O (8)- Complele recovery

O (C) Respiratory dislress syndrome O (D) Fetal demisc in the neXI pregnOlncy O (E) Hemolytic anemia Ihroughoul infancy

O (E) Pregnancy-induced hypertension

For each of Ihe dinical histories in queslions 13 and 14, malch the most dosely associated infeclious agent Ihal may cause infection in Ihe neonatal period: (A) ClItldidl/ lIlbiclIfl$

(8) (C) (1)) (E) (F)

17. A large "pon wine slain" involves lhe left side of the face of a 3-year-old child. This irregular. slightly raised, red-blue area is nol paillful, bul is very disfiguring. Hislcr logically. this lesion is lnrnil like1y composed of a prolifer. alion of

Cytomegalovirus Groop 8 streplococcus Herpes simplex virus Human immunodeficiency virus (HIV)

O (8) Lymphatics O (C) Fibroblasts

Listerill ntot1OC)"Iogelles

O (E) Capillaries

(G) ParvO\'irus (H) Rube.lla virus (1) Toxopfasllul gOl/di; (1) Tre¡xmemtllXlllidum

13. A 33-year+old femOlle is in Ihe 32nd week of pregnancy when she nOlices lack of fetal movemelll for 3 days. No fettll heart Iones can be auscultalw. The fetus is del ivered slillborn. AUlopsy reveals scauel'ed microabscesses in liver, spleen, brain. and placenla. No congenilal anomaJies are fOUlki. 1llere have been similar fetal losses within the same community over the pasl 3 months. ( ) 14. A neonale bom al 36 weeks' geslation manifeslS hydrops felalis and hepatosplenomegaly. 1ñe baby is aloo found to have a hemoglobin concentration of 9.4 gldL and plalelet COllIll of 67,OlXY,.u.. 11Je baby has generalized icteros alxl scauered ecchymoses of lhe skin. Death occun; at 14 days after birth. AUlopsy reveals exlensive subependy· mal necrosis with microscopic evidence fOl" encephalilis. Wilhin Ihe areas of necrosis are large cells comaining inIrOlnuclear inclusions. ( )

O (A) Neuroblusls O (D) Lymphoblasls

18. 1bere is no screening le<;t lO delecl carriers of mUIalions in lhe cystic librosis gerle (CFrR) because of which of lhe following Iimilations?

O (A) Mosl mUIOllions in Ihe CFTR cannol be delecled by polymerase chain reaction (PCR). 0(8) Fluorescenl in silu hybridizalion technique for de-

tecting Ihe mUlalion is very labor inlensive and expensi,'e. O (C) 11Jere are se,reral hundred mutalions in !he CFTR gene thal can give rise lo cysric librosis. O (D) Molecular teChniques can delect mUlations in CFTR only when bolh copies of the gene are abnormal. O (E) 1he frequency of helerozygotes in the population is less lhan I in IO,<XX>.

15. A baby is bom premalurely at 32 weeks' gestOltion. The infam requires 3 weeks of intubation with posili,'e pressure ventilation allel dies at 4 months of age. Al autopsy lile infant's lungs soow bronchial squamous metaplasia wilh peribroncllial fibrosis, interslitiOlI fibrosis, aOO dilalion of air spaces. WIlich of the following condilions besl explains Ihese findings?

O (A) Sudden infant death syndrome O (B) Venlricular seplal defect O (C) Cyslic fibrmis

O (1) Long il~ury due lO positive pressure vemilatioll O (E) Pulmonary hypoplasiOl 16. A baby boro al lerln has become mildly icleric, with a neonatOlI bilirubin collcenlralion of 4.9 mgldL over lhe first few days of Jife. No morphologic abnormalities are foond on pllysical examinOllion. '(be pregnancy and lhe delivery were uncomplicaled fOl" !he 18-year-old mother. 11le direct Coombs lesl on Ihe baby's red blood cells is posili\'e. The baby's blood Iype is A negative. Based on

19. The renal lesion shown here was presenl in a 3-yearold child who had a palpable abdominal mass. The child Ialer had abdominal diSlenlion fmm bowel obstruction. Which of the following congenilaJ disorders grea1ly increases lhe risk of developing this lesion?


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GENERAL PATHOlQGY

o (A)

Edwards syndromc O lB) MarCan syndromc O (C> Beckwith~ Wiedeman/l syndrome O (O) McArrlle syndromc O (E) Klinefellcr syndrome 20. At birth, a male Ileonate is noticed lo be small for 38-weeks' gestarional age. Physical exalllination revcals microcephaly. shol1 palpcbral fissures. and maxillary hypoplasia. Which of Ihe following condilions is mosl likcly lO lead lO Ihese findings? O (A) Congenilal rtlbella

O (H) O (C) O (O) O (E)

Placema previa Malernal diabeles mellilus Trisorny 21 Fetal alcohol syndromc

21. Al I~ week,s' gestation, ultrasoond re\'eals hydrops fetalis. bul no malfonnalions are fooro. This is lile Ihin! pregnancy foc" the 20-year-old molher, whose preViOllS pregnancies a11 endcd in lenn (¡ve binh~. The baby is Ii\'eborn al 36 weeks bul has a cord blood hemoglobin level of unly 9.2 g/dL. and the 10lal bilirubill concenlralion is 20.2 mgJdL. Whieh of Ihe fol1owing laboralOry lesl findillgS besl explains Ihe pmhogellesis of Ihis baby's disease?

O

(A) Posili\'(' Coombs' lesl rcsult on cord bl00d O (H) Elevaled malernal serum a-fetoprOlein le\'el O (e) Posilh'C maternal heparitis B surface anligen

tic leslS could ha\'C bcst prcdicled lhis baby's rcspiralory dislrcss?

O (A) Malernal scrum leve! of u-feloprotein O (B) AmniOlic fluid phospholipid analysis O (C) Chromosomc analysis O (O) Coombs test 00 cord bl:ood O (E) Genetic analysis ro..- cyslic fibrosis gene For each of lhe descriptions of a palien! with a genelic disease in queslions 25 and 26, selccl the mosl closely associaled gene prodUCI Ihat is likely lO be abnomlal or absenl with thal disease? (A) Adenosillc deaminase (Bl Alphal-anlitrypsin (C) Oyst.rophin (O) Factor VIII (E) Fíbrillin (F) Galactosc·¡-phusphate uridyllransfera.se (G) Globin chains (H) Glucoccrcbrosidase (O Glucose-6-pllosphalélSC (1) Hexosaminidase (K) Lysosomal acid mallase (L) Muscle phosphorylase (M) Phenylalanine hydroxylase (N) Speclrin (O) Sphingoll1yelinase

O (O) Oiminished glococcrebmsidase aclivity in fetal cells

25.

O (E) P1acenlal culture posili\'e foc" f..isle";a monocylo-

has developmemal delay wilh memal rctardation and inability lO walk. The child's urine has a distinctly "lTIOUsy" odor. On physical examinalion, Iherc i~ no Iympha-

gel/es

22. A 3-monlh-old infallt was found dea<! by his mother late one e\'ening. When she pUl him in bed only an hour before, he had shown no signs of dislress. The baby's lenll binh hOO followed an uncompliealed pregnancy_ and he ha<! been feeding well and gaining weight nonnal1y. What is lhe medical exall1iner mosl likely to filld al aUlopsy?

O (A) Hyaline membmne disease O (B) Cerebral cYlomegalovirus

O (C) Tetralogy of Fallol O (fJ) Adrenal neuroblasloma

A 3-year-old, lighl-skinned African-American child

deoopathy mic_ (

Uf

hepau)!¡plenomegaly. The child is noe :me-

)

26. A teml infam develops vomiling wilh diarrhea a few days arter birth. By Ihe end of lhe fi~1 wcek of life, the neonate is iclcric. Cataracts de\'e1op a Illonth later. Develollmenlal milcstones are not bcing mel al I year of age. The baby succlllT1bs lO Eschericltitl colí septicemia al age2.( )

O (E) No abnormalities

23. A 25-year-old g.ravida 3 para 2 female in her 39th wed: of pregnancy feh no fetal mO\'ement for I day. nI<: baby was stillbom on vaginal deli\'ety a day laler. Microscopic examinaliun of Ihe placenta re\'ealed rnaIked acUle chorioamnionitis. Which of Ihe following infectious agents was IllQSl likely responsible foc lbese e\'cnts?

O (A) Cytomegaloviru!> O (B) T. p(ll/idwn O fC) Herpes simplex virus O (O) Toxoplllsmll gOlldii O (E) Group B Srreptococc:w;

24. Soon afler birth, a baby of 31 weeks' gcslalion de\'e1ops respiralory dislrcss requiring intubalion wilh posilive pressure ventilation. Ullrasound al 20 weeks' gestation hOO 1'C\'ealed no abnormalities. Howe\'er, premature labor experienced by lhe IIJ-)'ear-old molhcr loo lo the emergelll vaginal delivcry. Which of !he following prenatal diagnos-

27. A srillbom hoy of 33 wceks' gestaliollal age was sc\'ere1y hydropic. ",be pregnancy was reportcd by lhe mother, a 19-year-old primigra\'ida. lO be uncomplieatcd,


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and an ultrolSOllnd performed at 16 weeks hild shown no abnonnalilies. lbe Olother had only experienced a mild msh illvolving her face around 18 weeks' geslatiou. At autopsy, lhe stillborn is found to llave no cougenilal mal~ fonnations. although lhere is cardiomegaly. From lhe hisloIog.ic appear3nce of lhe bolle marrow sf10WIl in lhe figure. the mQSI likely cause f~ these filldillgs is

O (A) Maternal IgG crossing lhe placenta O (B) A chromosomal anomaly of the felus O (e) A congenital neuroblastoma O (D) lnheritance of IwO abnonnal CFfR genes

O (E) An infeclion wilh parvovirus B 19 28. A 25-year-old female has had four pl'evious first- and second-trimestel' spontaneous abonions. She is now in lhe 161h week of her fiflh prcgnancy. She has hm.l no prenatal problems so far. Her blood Iype is A IXlsilive, lhe serologic test for syphilis is llegative, and she i¡; rubella immune. Which of the followillg labor.ttory tests would be mosl useful for determining lhe cause of recurrent felal loss in Ihis palient?

O (A) Maternal O (8) O (e) 0(1) O CE)

senJm a-fetoprotein determination Genetic analysis f(W the CFfR gene Malemal serologic lesl for HJV Amniocenlesis with chromosome analysis Maternal serum antibody screen

29. Examination of a stillbom fetus delivered at 20 weeks' gestation reveals an abdominal wall defccl laleral lo che wnbilkal cord insertion. ITwked ver1ebral scoIiosis, and a Ihin, fibrous band constriCling the righe lower extremilY. which lacks fingers. None of lhe other three pregnancies. whkh ended in lenn binhs f(W lhe 31-year-old mother, were similarly alfecled. These findings are mosl Iypical fer

O (A) Trisomy 18

DlSEASES OF INFANCY ANO CHILDHOOD

93

O (A) Single-gene mUlations of large effect O (H) Malernal infections O (C) Maternal drug use O (O) lllleraction of multiple genes with enviromnental

O

factor.; (E) CIlromosomal aberrdtions resuhing froen mitotic er-

ron early during gestation 32. A morphologically normal looking ilúant bom at 37 weeks' gestalion weighs 1500 g. This weighl is below the 10th percentile for age. Further ex.amination reveals lhat, although the crowrr-heel length is below normal fa !he gestational age, head circumference is normal. Which ol: !he following CalL<;e5 is mosl likely to be responsible for Ihi.~ condilion1

O (A) Transplacental spread of malernal toxoplasmosis O (B) Nondisjunction of chrolllosomes during maternal

oogenesis

O (e) Nondisjunclion of chrolllosomes within Ihe trophoblasl O (D) Failure of fetal kidneys lO develop O (E) Inherilance of mutant alleles al lhe cystic fibrosis lransmelllbmne conduetance regulalor (CFTR) from

both parents 33. Examinalioll of a 2O-week-gestalional-age slillbom fetus shows amruotic bands tIlat ex.tend fmm amputated fingeB aOO loes of boIh feet and anolher band in a cleft through !he righl aspect of lhe sl.-ull. How ",ould you c1assify lhe underlying abnonnalilY in Ihis C'dSe?

O (A) Disruption O (B) Malfonnalion O (e) Temlogenesis

O (D) Inflammation O (E) Deformation

5cJ-

O (H) Oligohydramnios

O (C) Mulelllal fetal Rh illCOm¡><llibility O (O) Amlliotic band syndrome O (E) Congenilill cytomegalovirus infection

30. Synlhelic retinoids can be successfully lL'ied 10 !reat acne. However. pregnant women are advised against using this medication because retinoic acid can cause congenilal malfonnalions. lhe teralogenic effect of retinoic acid is related lO its abilily to affect which of lhe followillg proc. esses?

34. An 18-monlh-old male child is not gallllllg weighl nonnally. His motller noles Ihal Ihe child's abdomen seems larger. Thefe are increased Ievels of vanil1ylmandelic acid (VMA) and homovanillic acid (HVA) in Ihe child's urine. An alxlominal ullmsound .sean is mesl Iike1y to reveal a mass in Ihe O (A) 0(8) O (C) O (O)

O

Liver Adrenal KKlney

Spleen (E) Colon

O (A) Increasing the risk of maternal infections O (8) Reducing the resistanee of fetus lO transplacelltal

infectiOlls O (C) lncreasillg the likelihood of aneuploidy during cell division O (O) Abnormal developmenl of blood vessels in the placenta O (E) Disrupting lhe pauem of exprcssion of homeobox genes 31. Which of Ihe following etiologic faetors is the most common CllUse of congenital malfonnations?

35. A baby bom al terro develops abdominal distention in lhe first week of life. Meconium ¡Ieus is diagnosed. Subsequenlly, !he infanl has persistenl steatormea and fajls to develop normally. Which of the following labaratO!)' tesl findings is mesl likely relaled 10 !he infam's underlying disease:

O O O O O

(A) (H) (C) (D) (E)

Oecrcased serum thyroxine level Positive HlV serology Elevuled sweat chloride Increased urine homovanillic acid level Hyperbilirubinemia


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94

Pon 1

GENERAl PATHOlOGY

likclihood of SIDS. 1ñe only faclor that argues againsl SII)S in this case is the age of 18 months.

BP6205 PBD6481-482 3. (B) This premalllre newronl does nol ha\'c sufficienl Iype 11 alveolar cell surfaclant production. As a resull, Ihe baby has de\'e1oped hyaline mcmbrane disease. If the baby were to survi\'e but go on lO develop broochopulmonary dysplasia, fibrosis would be aJ>Po'lfenl. An alveolar lransudate or exudale may acCOlllpallY a \'ariety of condilions bul is 001 lhe key feature of hyaline membrane disease. l\'lucus plugging occurs in c)'stic fibrosis. but this is oot a comlnon finding in neonatal lun~.

BP6204-205 PBD6471-472 4. (O) The abnomlal chloride ion transport in cystic fibrosis results in abnonnal tllllCUS secrelions in pancremic ducts lhat caUl'e plugging with subsequeJlI acinar atrophy with fibrosis. GalaclOse-l-phosphate uridyl Iransferase deficiency gives rise to galactosemia. PatienlS with this condition have li\'er dalnage bUI no p311creatic abnomlalities. Abnormalities of LDL recep'or with familial hypercholeslerolemia lcad lo acceleraled atherogenesis. Abnormal fibrillin is a fealure of Marfan syndrome. Phenylkelolluria resulls fmm a deficiency of phenylalanine hydroxyla..e. 36. A baby bom al 36 weeks' gesulIion shows lhe facial fealures and posilioning of extremities shown heTe. 1be baby SQOn de\'elops se\'ere respirarory distress. Which of the following COfKlitions besl explain... these findings?

O (A) Congenilal rubella infcetion O (B) Bilalernl renal agenesis O (C) Maternal diabeles mellilus O (D) Hyaline membrane disease O (E) Trisomy 13

ANSWERS l. (A) The baby is small for gestatiollal age because of intrauterine growth relardation. 'Iñe asymmetric growth suggesls a malernal or placental cause. Felal problems such as chromosomal abnonnalities. infections. a.nd erythroblas--tosis are likely to prOOuce symmetric growth relardation. Babies rom to diabetic mothers are Iikely to be larger than normal for gesuuional age. Felal hydrops can aceompany congenilal infections and erythroblastosis. which may artificially increase fetal weight.

BP6 203

PBD6 461 -462

2. (C) AlIhough the cause of SIOS is unknown. certain risk factors are welJ esrablished. A.mong lhese is age. SIDS occurs between I month and I YC'dr of age. Ninely per cent of SIDS deaths occur during the firsl 6 momfls of Iife. A.lrhough agc alone cannot exclude SIOS in this case, a11 olher factors pro\'ided iocrease the risk of SIDS. Male sexo African-Alllcrican race. low socioeconolllic background of p:lrcnts, and absence of anatomic abnonnality all favor the

BP6207-209 P8D6 477-481 5.

(O) AmpLification of lhe N-m)'c oncogene occurs in about 25% of neuroblaslomas. and the greater lhe number of copies, the worse is the prognosis. Such N-mJc amplification lends to occur in neuroblaslomas with a higher stage or wilh chromosomc Ip deletions. Hyperdiploidy or near triploidy is usuaUy associated wilh lack of N-mJc amplification. absence of IP delelion, and high le\'els of nerve gmwlh factor receplor Trk A expressioll. AII lhese bode for good prognosis. The presence of ganglion cells is con¡,islent with a beuer differenliation and beller prognosis; saine IUlTlOrs may differemiate o\'er time and becomc ganglionellromas under the inftuence of Trk A. Renal malformations are nol relaled lO neuroblastomas.

BP6211-212 PBD6486-487

6.

(i\) Teratomas are benign neoplasms COmjXlse<\ of lissues deri\'ed from embryonic germ layers (i.c., ectodenn. mesodenn, or endodenn). Teratomas occur in midline locations, and the sacnx:occygeal arca is the most common. Less comnlOn immature or frank.ty malignanl teratomas with neuroblastic elements can occur. NeuroblaslOmas ~ malignant childhood IUlTlOrs most commonly arising in lhe adrena1. Hemangiomas form irregular red-blue skin lesions Ihat are fiat aJKI spreading. Lymphangiomas are mosl oflen lalernl head aJKI neck lesions in childhood. Hamartomas are 1l\itSSCS composed of liK'iUes nonnally foond at a particular sile. and lhey are rareo

BP621O-211

P8D6484

7. (O) 1ñe immaturity of the fetal lungs befare 35 lO 36 weeks' gestalion can be complicaled by lack of sufficient surfactant to provide for adequate \'enlilatioll after birth. This can resull in hyaline mcmbrane disease. TeSIS on amniotic nuid before binh. including lecilhin-sphingomyelin ratio, lluoresccncc polarization. ami lame\lar body


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coonls., are useful lO predicI lhe degree of pulmonary immalurity. Malemal toxemia and oongenilal ilúect.ions may lea<! lO hyaline membrane disease if the birth occurs premalurely as a oonscquence of these oondilions, but lhey 00 llOI directly affeel lung lTIa1urily. Oligoo)'dramnios may re~ sull in neonatal respiralory distress through lhe mechanism of pulmonary hypoplasi:l..

DlSEASES OF INFANCY ANO CHILDHOOD

95

canlly alTeel surfactaJll prodoclion. Oligohydram.IDos leads to constriction in ulero thal culminales in pulmonary hypoplasia, noI decreased surfaetanL Maternal hypertension may reduce placental fu"clion and increase growlh rctardation bul typically 00es llOI bave a significanl effect on the production of surfaetant.

BP6 204 PBD6 471-472

BP6204-205 PBD6471-472

8.

(C) Rubella infeclion in Ihe firsl trirnesler, when 01"ganogenesis is occurring (4 lO 9 weeks' geslulion), can Icad lo congenilal heart defeels. DispemlY leads lO lriploidy, a oondition Ihal mrely results in a ¡ive birth. Thalidomide use in the pasl was an important cause oC malfonnalions (alrnost invariably, prominelll limb deformilies). lbe use of Ihalidomide as an immunosuppressive agenl is under considerdl.ioll. Erythroblaslosis fetalis leads to fetal anemia with oongeslive heart failure alKl hydrops 001 llOI lo mal~ formations.. Folale deficienC)' is mosl likeJy lo be associaled wilh neural tube defccts.

BP6201-202 PB06466-467 9. (1» Surfactanl is synlhesized by Iype 11 pneumocytes tha! hne the alveolar sacs. 1lley begin lo differenliate after lhe 26th week of geslation. These cells can be recognized on electron microscopy by the prcsence of I¡¡mellar bodies. Surf¡lctanl proouction increases greatly after 35 weeks' gestalion. Other slrUClUres in the lung do nOI synlhesize Ihe phosphalidylcholine aOO phosphalidylglycerol compounds lIlal are importan! in reducing alveolar surface lension.

BP6204-205 PBD6471-472 10. (8) Most malformalions, particularly those lhal are isolaled defects, bave no readily identifiable cause. 1ñey are believed lo be cause<! by lhe inheritance of a eenain number of genes and the inlernction of lhose genes with environmenlal facton;. 1ñeir lransmission follows lhe rules fOl" multifaetorial inheril3l1ce. The mle of recurrence is believed lO be in lhe mnge of 2% lo 7% and is the same for atl firsl-degree relatives, rcgan.l.less of sex and rclationship lo the index ca<;e.

BP6201-202 PBD6466-467 11. (A) Persons with phenylkelonuria survive lO rcproduclive age with good mental fWlCtion when they are trealed from iufaney wilh a phenylalanino.. free diet.. MIel" neurologic de\-elopment is compleled in childhood, lhe diel is no longer needed. Howe\-'er, a pregnanl woman wilh phenylkelonuria has high le\-els of phenylalanine, which can damage the developing fetus. Going on a phenylalanine-free diel is a majar sacrifice, because lhere are few food.'l lbal bave no phenylalanine. (Persons wilhoul phenylkelonuria can find drinking e\'en 100 mL of a liquid phenylalanine-free meal lO be difficult.) Phenylkelonuria does nOl alfeel tissues other than the CNS, nnd Ihere are no lTullfonnalions in children wilh phenylkelonuria.

BP6 164 PBD6475-476 12. (C) The hyperinsulinism in the fetus of a diabelic mother suppresses pulmonary surfactant prodoclioll. Corticosleroids stimulale surfac:lant prodoclion. Infection roay increase the risk for premature birth bul does nol signifi..

13. (F) Lisleriosis can be a congenilal infectiOll. Preg.. nam women may have only a mild dillrrheal Hlness thernselves. bul the organisrn can prove devaslaling lO Ihe fetus or neonate. Mini-epidemics of Iisteriosis are often Iinked lo a cOlllaminaled food source, such as dairy products. chicken, and hol dogs. Neonatal meningitis can be caused by L mOllocytoge1les.

PBD6378 14. (8) Allhough aboul 90% of cytomegaJovirus-i1úected neonales have no overt disease, infeclion can be extensive in sorne cases. 1ñe brain is oflen involved. allhough lhe irlClusions can be found in many organs. "The renal lubular epilhelium can be infected, and large cells wilh inclusions can be seen with urine microscopic examination in same cases. Cytomegalovirus manifesled in neonales may have been acquired transplacenlally, al birth, or in breasl milk.

PBD6376 15. (D) High-dose oxygen with posilive pressure ventila.. tion can cause injury to immarure lungs, leading lO Ihe chronic lung disease knoWll as bronchopulmonary dysplasia. With SlDS, no analomic abnormalities are foond aE aUlopsy. A VSD could evenlually lead lO pulmonary hyper.. lensioll from shuming. Pulmonary manifeslalions of cystic fibrosis are nol manifesl al birth or in infancy. MortalilY wilh puhoonary hypoplasia is grealesl al birth.

BP6205 PBD6472-473 16. (B) This is a mild hemolytic anemia, probably an ABO incompalibililY wilh malernal blood Iype of O. so Ihal anti . . A anlibody coato¡ felal cells. Allhough mosl anli-A alld anti-B antilxxlies are IgM, in abaul 20% to 25% of pregnancies there are also IgG antibodie..o¡, which CfOS.,.O¡ the placenla in sufficielll liler (O produce mild hemolytic disease, al leasl in masl cases. Al term, lhe bilirobin in Ihis case is noI higl1 enoogh lO produce kemieterus.. Al term, respiralory distress is unlikely. ABO incompalibililies are I)()( likely lO have as serious conscquences fOl" subsequem pregnancies as Rh incompatibility. As lhe baby malures, the maternal antibody diminisf1es.

BP6 206 PBD6 473 17. (E) The masl common lumor of infancy is a heman.. giorna, and lhese benign neoplasms form a large percenlage of childhood lumors as well. Though benign, they can be large and disfiguring. A proliferalion of neuroblasls occurs in lleuroblastoma, a COll1ffiOn childhood neoplasm in Ihe abdomen. Lymphangioma is anolher cornrnon benign child.. hood tumor seen in the neck, mediastinum, and retroperiloneum. Fibromatoses are fibromatOtlS proliferdlions of sofl (issues lbal form solid rnasses. Lymphoblasts as part or


96

Port 1

GENERAl PATHOl.QGY

leukemic infillrales 01' Iymphomas are not likely lO be seen in skin, but mediastinal mas.'ieS may be seen.

brane disease occurs al birth wilh premalurity. COIlgenital neopla.<;ms are a mre cause rOl' suelden death.

BP6210 PBD6 483

BP6205 PBD6481-482

18. (e) When a genelic disease (e.g., cysti( fibrosis) is caused by many different mulalions. no simple screening teSt Ihat can delecl all lhe mUlations can be perfonned. Although 70% of palienL'l Wilh lhe disease have a 3-ba.-.e pair delelion lhal can be readily delected by PeR, lhe remaining 30% are caused by several hundred a1Jelic form'l of CfTR. To detect all would require sequencing of lhe CI..--rR genes. "Ibis prohibits mass screening.

23. (E) The acule illflammation suggesls a bacterial infeclion, 3nd group B Strel)IOCOcCII.~, which can colonize Ihe vagina. is a common cause. 'Ibe infeclion can develop quickly. Cytomegalovirus. syphilis. and loxoplasmosis are congenital infectiOlls lhal can cause slillbinh. bul they are more likely to be chronic. Herpelic infeclion.<; are most likely to be acquired by passage mrough the binh canal.

BP6207-209 PBD6478-479 19. (O 'Illis uncommon sYlldrome carries 3n increased risk for lhe developmenl of Wilms' lumor, which is a childhood neoplasm arising in the kidney. Renal anomalies such as horseshoe kidney can be seen with Edwards syndrome (trisomy 18) but not neopla.'lms. Likewise. Marfan syndrome is not associaled "Vilh an inereased risk for ma· Iignancy. Children wilh a deficiency of myopnosphorylase in McArtlle syndrome can have muscle cramping bul are not at risk for neoplasia. The 47,XXY karyolYPC of Klinefeller syndrome does nol carry 1m increased risk for renal lumofS.

BP6213-214 PBD6488-489 20. (E) Alcohol is perhaps une of the most commQf1 en· vironmenlal leratogens affecling feluses. allhough lhe effects can be subtle. 1ñe children SO afTecled tend lO contirme lo be developmenlally impaired. Congenital rubella, which has ils major ellects during orgallogellesis in Ihe first trimesler, results in more prollounced defecls, induding congeniwl hean disease. Placellla previa, a low-Iying placenta al or nenr lhe cervical as, can cause significant hetTlOfl"flage al the lime of delivery. or uteroplacental insufficierey with growth relardation before delivery. Placental cause.'l of inlraulerine growth relardation re.'luh in asymmel· ric gmwth retardation with sparing of the brain. Maternal diabetes often results in a larger baby, and malfonnalions lllay be present as well. 'Ibe findings of trisomy 21 are subtle at bil1h but typically indude bmchycephaly. 1\ot microcephaly.

BP6 202 PBD6467 21. lA) 'Iñe baby has erythrobluslosis fetalis fmm mater· nal anlibody coating felal cells and causing hemolysis. The fetal anemia \eads lo congeslive heart failure aOO hydrops. Hemolysis resulL<; in a \'ery high bilirubin. A high maternal serum level of a-fetoproteill suggesls a felal neura! lube defec!. and neuml lube defects are Ilot associaled wilh hydrops. Viral hepatitis is not a perinatal illfecliOll. Diminished glucocerebrosidase activity causes Gaucher disease. 1ñh. does 001 lead to perinalal liver failure oc anemia. Usteriosis oc Olher congenital infection.<; may produce hydrops and anemia, although 001 of Ihis se\'erity.

BP6206-207 PBD6473-475 22. (E) The evellls suggest 5105. 'l11e cause is ullknown, and by definilion lhere are 110 significanl gross or microscopic aUlopsy fiOOings. InfanlS with cOllgenital anomalies or infeclions are unlikely to be doing \\'ell. Hyaline mem-

BP6 203 PBD6470 24. (B) 'Ole bllby mosl likely had hyaline membmne dis~ ease from felal lung immalurity alld lack of surfactanl. Surfactant consists predominantly of dipalmitoyl phosphati~ dylcholine. The adequaey of surfactanl production can be gauged by lhe phospholipid contelll of amniOlic fluid be.. cause fetal lung secretions are discharged into the amniotic fluid. The malernal serum alpha-fetoprotein is useful to prediet felal neural lube defecls and chromosomal abnormalities. Chromosome analysis may help lo predict problems afler binh or the possibility of fetal loss. The Coombs teSI may help lO delemune presence of erymroblaslosis fetalis. Cystic fibrosis does nol cause respirnlory probJems at birlh.

BP6204 PBD6 471-472 25. (M) The child has phenylkelonuria. 'Ibe absence of phenylalanine hydroxylase genes give rise lO hyperphenyl~ alaninemia. which impairs bmin development and can lead lO seizures. The block in phenylalanille metabolism results in decreased pigmentatioll of skin and hair. h also results in the formation of inlennediale compounds, such as phenylaeetic acid, lhal are excreled in wine and impart to it a "mousy" c:xlor. Because of lhe devastating consequences of mis illherited disorder and because it can be treated with a phenylalanine-free diel. this is one of the disea'leS tested for at bil1h, even lhough it is mre.

BP6 184-185 PBD6475-476 26. (}) Tbe baby has findings associated wilh gaJoclose~ mia, an aUlosomal recessive condition mal can be lesled for at binh. Hislologically. the I¡ver of affected infanlS has marktd fany change. and portal fibrasis mal iocrea.ses over lime. In addition to hepatic lesions, lhe palients have diarmea ane! develop ealaracts. For unknown reasons. they are very susceptible lO E. col; seplicemia.

BP6 185 PBD6476-477 27. (E) 'Iñe erylhroid precursors demonstrate large pink inlranudear inc!usions typical for par"ovirus. In adults. such an infection Iypitally causes oofiflh disease." whicb is self~limited. However, tbis is one of lhe 0'0" infections in the TORCH mnernonic describing congenilal infeclions (toxoplaslTlosis, vther infections. 111bella, cYlomegalovirus infeclion. and herpes simplex infection). Parvovirus infec· tioll in the Felus (llIl lead LO a profound felal anemia with cardiac failure and hydrops fetalis. Erythrobla.~losis fela!is is unlikely lO aceur wilh Ihe hrsl pregnancy. and lhere is only erythroid expansiono not erythmid inclusiol1,<;. AI~


< not tor Ea.le! > < He AIIA npo.."."". ! >

Chapter 10

though a variery of chromosomal anomalies-monosomy X in particular-may lead lO hydrops, malformations are typical. Congenital lumors are an uncommon cause for hydrops, and they should produce a mass lesion. Cyslic librosis does not affed erythropoiesis. PBD6470,474 28. (D) Multiple fetal losses earlier in geslalion suggeSI the likelihood of a chromosomal abnonnalitY-lhe mother or father may be the carrier of a balanced tmnslocalion. The maternal serum level of a-fetoprolein can help find cases of fetal neuml lube defeds, but this is nol a cause for early fetal loss. Maternal HIV infection is nol a cause for significanl fetal loss. Cyslic fibrosis produces post natal problems. Because the molher is blood Iype A posilive, fetal loss wilh erythroblaslosis fetalis is unlikely. BP6214-215 PBD6 182 29. (D) This is a classic example of an embryonic disruplion Ihat leads lO Ihe appearance of congenilal malformalions. Fibrous bands and possible vascular insults may explain such findings, which faH in Ihe spectrum of a "Iimb-body wall complex" thal includes amniotic band syndrome. In trisomy 18 and olher chromosomal abnonnalities, an omphalocele is Ihe moSI common abdominal wall defecl. Oligohydramnios wilh diminished amniotic Huid leads lO defonnalions, nol disruplions. Rh incompatibilily can give rise lo erythroblaslosis felalis. which may manifesl as hydrops felalis. Fetuses affecled by hydrops presenl with widespread edema and inlense jaundice. A variety of malforma1Íons may occur as a result of congenital infeclions, bul nol amnionic bands. BP6 200 PBD6 465 30. (E) Retinoic acid embryopathy characteri:red by cardiac, neural, and craniofacial defecls is believed lo result from Ihe ability of retinoids lO affecl the expression of homeobox (HOX) genes. These genes are importanl in embryonal patterning of limbs, vertebme, and cmniofacial slruclUres. PBD6469 31. (D) Mullifactorial inheritance is Ihe single moSI common known cause of congenilal malformalions. This information is useful for advising patienls of Ihe Iikelihood of rccurrence. Mosl cases of congenital anomalies fmm mullifactorial inherilance have reCUITence risk thal ranges from 2% lo 7%. AH the olher listed causes added logether are about equal to multifaelorial inheritance. BP6201-202 PBD6 466-467 32. (e) The infanl has asymmetric inlrauterine growlh relardalion Ihat can resull fram placemal cause..<¡. Confined placenlal mosaicism, resulting fram genelic elTOfS in dividing IrophoblaSIS, is responsible in 90% of cases. Transplacental spread of infection to the felUs would give rise to proporlionale inlraUlerine growlh retarclalion (IUGR). Non· disjunction of chromosomes during malernal oogenesis

DtsEASES OF INFANCY AND CHllDHOOD

97

would affect Ihe felUs very early on and would also result in symmetric growlh retardation. Failure of kidneys lo develop can cause oligohydramnios, and the felus would be abllorrnal in appearance. Mulation al both alleles of lhe CFTR gives rise lO cyslic fibrosis. This is nol associaled wilh inlraUlerine growth relarclalion. BP6 203 PBD6461-462 33. (A) This is amniotic band syndrome, a subset of limb-body wal1 complex, which results from embryonic disruplion wilh deslruction of body regions and formation of fibrous bands. A malfonnation. such as congenilal heart disease, results fram an error in morphogenesis. Chromosomal abnorrnalilies can be accompanied by a variety of malfonnations. Infiammalion can produce malfonnalions, as wilh congenilal syphilis, or lissue destruclion, a<¡ wilh congenital cytomegalovirus infection. Defonnations result from mechanical rorces on organs and lissues, an example of which is the facial fealures seen with oligohydramnios. BP6200-201 PBD6464-465 34. (B) The presence of an abdominal mass and metaboliles of calecholamines in Ihe urine slrongly indicate a neuroblasloma. ll1e adrenal is Ihe mosl common location for a neuroblasloma. Extra-adrenal paraganglia are olher common siles. Hepaloblastomas of Ihe liver and Wilms' lumor of the kidney are childhood tumors but do not secrete catecholamines. Splenic neoplasms are rare al any age. Colon cancers are seen in older persons more commonly but occasionally occur even in leenagers (wilh an inheriled mulalion in Ihe APC gene). BP6211-212 PBD6485-487 35. (e) The findings are typical for cystic fibrosis, which is an inherited defecl in chloride lransporl. Crelinism from hypolhyroidism resull<¡ in impaired CNS and skelelal developmen!. A baby with eongenital HIV infection may have a variely of infections. The increased urine homovaniUic acid is a fenlure of neumblasloma. a mass lesion lhat could also cause bowel obStruction bul nol meconiull1 ileus. Neonalal jaundice has a variely of causes, inc1uding lhe inheriled disorder called galactosemia. BP6207-209 PBD6477-4Bl 36. (B) The fiatlened face ~nd deformed feel .suggest oligohydramnios resulüng from renal agenesis. Fetal kidneys produce urine Ihat becomes Ihe amniOlic fluid. Pulmonary hypoplasia is the rale-Iimiting slep lO survival. Congenilal rubella can ¡ead lo a variery of malfonnalions, not deformalions. Babies born lo diabelic molhers have an increased risk of congenilal anomalies. Felal IUllg maturjty is Iypi~ cally achieved at 34 lO 35 weeks' gestalion, and hyaline membrane disease is unlikely at 36 'weeks. Trisomy 13 is accompanied by a variety of malformalions, including Ihose affecting Ihe kidneys. The exlernal fealures: however, are quile differenl, and Ihey almOSI always have midline defeclS such a<¡ den lip and palale and microcephaly. BP6 201 PBD6 465


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11 Blood Vessels

BP6 Chopter 10 - Blood Vessels PBD6 Chopter 12 - Blood Vessels

l. Atherosclerotic plaques are slowly but constantly changing in ways !hat protnole c1iniC"dl e\'ellts. Which of the plaque alterations liste<! is leas, Jikely lo loo lO ischemia in lhe comnary artery circulation?

O (A) Thinning of lhe media O (B) Ulceration of lhe plaque surface O (C) Thrombosi!'ó O (O) Hemorrhage illlo the plaq~ substance

O (E) Imemlittent plalelel aggregalion

2. lñe high-magnification microscopic appearance of Ihe kidney sIlown in lhe figure is lllOSl indicative of which of the following underlying condilions?

O (A) O (B) O (C) O (O) O (E)

Esdlt'richia coN seplicemia Hypertensioo Colonic adenocarcinoma SyphiLis Polyarteritis llOdnsa

For each of the palielll descriptions in questions 3 Ihrough 5, match the associaled leltered vascular di.sea<>e process:

(A) (R) (C) (O) (E) (F) (G) (H) (1) (1)

(K) (L) (M) (N) (O)

Angiosarcoma Aortic di!'óseetion Arteriovenou.s fislula Atherosclerotic aneurysm Gianl cell arteritis Glomus tumor Granuloma pyogenicum Hemangioma Henoch-Schonlein purpura Kaposi sarcoma Polyarteritis /lodosa Takayasu arterilis Telangiectasia Thromboangiitis obliterans Wegener granulomatosis

J. An 8O-year-cld male wilh a long histOl)' of smoking survived a :srnall myocardial infamion several years earlier. He has poor pulses peripherally in his Iowel" exlremities. His blood ~ssure is 1651100 mm Hg. Fa'iting serum glu· cose measureme.nts are in lhe range of 170 lO 200 mg/dL He has a 7-cm, pulsating ma.<¡s in the midline of his Iower abdomen. ( ) 4. A 7-year-old child presenl<; with abdominal pain. purpuric skin lesions. hematuria, and prOl.einuria. A skin biopsy shows necrotizing v3sculitis of small dermal vessels. A renal biopsy shows immune complex deposition in glo101


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« t<e AlUI rtpO.llo;l< \ > Port 2 OfiEASES Of C((GAN S'tSTEMS

meruli with sorne IgA-rich immunc eomplel'>es. Serum de· termination" are negalíve for anlineutrophil eYlopla<;mic antibodies (p-ANCA aOO e-A.NCA). ( ) 5. A 50-year-old male presellls wilh ehronic cough, tllISOpharyngeal ulcers. and a serum urea nítrogen Ic\'cl l)f 75 mgldL wilh a ereatinine conccnlmtion of 6.7 mgldl~ A nasal biopsy shows necrosis aOO necrolizing gmnulomalou.<; inflammalion. A lransbronchial lung biopsy shows a vasculitis in\'clving lhe small periphcml pulmonary arteries and artcriolcs. Granulomalous inf1ammalion is scen w¡thin ¡lIld lldjaeenl to srn¡¡1I arterioles. His serologic lilers for cANCA are high and rising. 1 ) 6. A 61-year-old maJe hOO a myocardial infan:lion ayear ago. Thi" was lhe firsl major illness in his life. He oow wams lO prevcnl another rnyocardilll infarclion, aOO he is ad\'iscd lO begin a program of excrcise aOO a change in his diclmy habils. Whieh of Ihe followillg serum labor:uury test findillgs wuuld give Ihe besl indicalion u yellr laler uf thc success of his die! and exercise regimcll1 O (A) Chole!i1crol O (B) Glucose

O O

(C) Pota....<;ium (O) Renin

el'ed media<¡tinum. Transesophageal echocardiography shows a dilate<! aortie root aOO arch wilh a tear in !he aonic intima 2 cm distal from the greal \'essels. From lhe microscopie <lppe<lTl.lllee of Ihe aort1.1 wilh elaslic slaill showlI in lhe figure. the most Iikely underlying distase is

O (A) Se leroderrnll O (8) Diabetes mellitus

O lC) Hypenension (O) Mllrfan syndrome O (E) Wegener gmllulomatosis

O

8. A pulsalile abdominal mass is palpated in a 4o-yearold male who has had won;ening abdominal pain for thc past week. An abdominal compuled lomogrnphy (CO sean reveals a 6-cm fusiform enlargemenl of the abdominal aorta. He is taken lo surgery. and an abdominal aonic gmft is placed. 1ñe underlying disc<lsc pTlx:ess in his case is Illost likely O (A) Polyarterilis 1I<Xk>sa O (B) Obesity

O (C) Diabetes mellilus O (O) S}'stemic lupus el)'themalosus (StE) O (E) Syphilis

O (E) Calcium

Counc¡¡)' "f Ton¡

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Tc:ul.\ Soulh\<e>Il!Jn t>'kdical School. Dalias. TX.

A spongy. 2-cm. dull red. circumscribed lesion has been preselll s¡nee infancy 011 lhe upper ouler 1eft ann of a Io-year-old male. 111ls Ie.<;ion is excised. and the microscopic appenT<lllCe is shown here. This lesion is mosl likely lO be 9.

O (Al Kaposi sarcoma 0(8) Angiosarcoma

O (C) Lymphangioma O (D) Tela.ngieclasia O (E) Hemangioma

10. A phllrm3eemic¡¡1 eompany is trying lo de\'elop an ami-alherosderosis agellt. Which of the following mechallisms of aclion is Iikely to have lhe masl effecti\'c anlíalllerosclerotic errect7

O (A) Inhibits lhe relea<;e of platelel-derived growth factor 7. A 23-year-old maJe cxperienccs the suddcn onscl uf sc\'ere. sharp ehesl pain. A ehest ntdiograph reveals a wíd-

(POGF) aOO inhibits macrophage-rnediated lipoproteill oxidaliun


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Chapter 11

o (B)

PromOles ¡he release of PDGF and inhibilS macrophage+medialed lipoprotein oxidalion O (C) Inhibits the release of POGF and promotes macrophage+medialed lipoprotein oxi<!alion O (O) Oecreases Ihe level of high-density lipoprolein (HDL) and inhibits macrophage-mediated lipoprotein oxidalion O (E) Increases Ihe level of inlercellular adhesion molecule-I (ICAM+I) and vascular cell adhesion molecule-I (VCAM-I) on endothelial cells and increases endothelial permeability

11. Al aulopsy. Ihe thoradc aorta of a 73-year-old male has a dilated mot and arch. giving the intimal surface a "tree bark" appearance. Microscopically, the aorta shows an oblileralive endarteritis of Ihe vasa vasorum. Which of Ihe following labaratory lest lindings is most Iikely lO be found recorded in Ihis patienl's medical ret;ord?

O (A) High double-stranded DNA liter O (B) p-ANCA posilive al 1:1024

BLOOD VESSELS

103

logic consequence of smoking, hyperlension, and hypercholeslerolemia?

O (A) Endothelial injury and ils sequelae O (B) Conversion of smoolh muscle cells lo foam cells O CC) Alterations of hepatic lipoprotein receplors

O (O) lnhibilion of low-density lipoprotein (LOL) oxidalion O (E) Alterations of endogenous factors regulaling vaso-

motor tone 16. For aboul 5 years. a 55-year-old femule has unsighlly dilaled superficial veins over bolh lower legs. Which of lhe following complicalions is she mosl likely lO suffer as a consequence?

O (A) 5laSis dermatitis O (8) Gangrenous necrosis of the lower legs

O (C) Pulmonary Ihromboembolism O (D) Disseminated intravascular coagulalion

O (E) Atrophy 01" lower leg musdes

O (C) Sedimelllalion rale of 105 mm!h O (O) 4+ kelonuria O (E) Anlibodies againsl Treponema pallidlm¡

12. For the paSI 3 weeks. a 70-year-old female has been recuperating from a boul of viral pneumonia complicaled by bacterial pneumonia, during which lime she has been bedridden. She now has some swelling and lenderness of her righl leg, which is made worse on raising or moving this lego Her condition is best called

O O O O

(A) Lymphedema (B) Oisseminated inlravascular coagulopathy (DlC) (C) Thrombophlebitis (O) Thromboangiitis oblilerans O (E) Varicose veins 13. A 49-year-old male is feeling fine when he has his blood preSSllre checked for Ihe first time in 20 years. He is sllrprised lO find Ihal he has a pressure of 155195 mm Hg. He has had no serious medical problems and is laking no medications. Which of Ihe following factors is most Iikely lO be imporlanl in the inibation of Ihis form of hyperten. ? Slon.

O O O O O

(A) (B) (C) (O)

fncreased catecholaminc secrelion Renal relenlion of excess sodium Gene defecls in aldostemne melabolism Renal artel)' Slenosis (E) Increased production of alrial natriurelic faclor

14. A 50-year---old male presenls with angina pecloris. Coronal)' angiogr.l.phy reveals a (fixed) 75% narrowing of the anterior descending branch of the left coronal)' artery. Which of Ihe following cells is leas! likely to be involved in the palhogenesis of his cOTOnary artery lesion?

O (A) Monocytes 0(8) Smooth muscle cells

O (C) Plalelels O (O) Neulrophils O (E) Endolhefial cells 15. In lhe causation of atherosclerosis. which of the following events is considere<! Ihe 1110S1 imporlam direct bio-

17. The 35-year-old maje with Ihe skin lesions shown here is known lo have been infected with Ihe human immunodeficiency virus (HIV) for Ihe past 10 years. Which of lhe fol1owing addilional infeclious agents is mosl likely lO play a role in Ihe development of Ihese skin lesions?

O O O O

(A) (B) (C) (O) O (E)

Human herpesvirus 8 Epslein-Barr virus (EBV) Cylomegalovirus (CMV) Hepalilis 8 virus Adenovirus

18. An 80-year-old male diabelic has a 7·cm, pulsaling mass in Ihe midline of his lower abdomen. He has poor pulses in his lower extremities. Which of Ihe following complicalions of aOrlic atherosderosis is responsible fOl" Ihe development of Ihis lesion?

O O O O O

(A) (B) (C) (D) (E)

Ulceration of alherosclerolic plaque Thrombosis overlying alherosderotic plaque Hemorrhage inlo Ihe plaque substance Atrophy (thinning) of the media Cyslic degeneralion of the media along wilh fragmentation of elaSlic fibers


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DISEASES OF ORGAN SYSTEMS

19. A 50-year-old male develops lhe sudden onsel of excruciating pain in Ihe chesl and back. Physical examinalion reveals diminished radial pulses bilaterally and normal femoral pulses. 'l1le cheSI radiogmph reveals a widened mediaslinum. Which of the following underlying conditions is most likely lo be eliologically related to Ihis patienl's acule problem?

O (O) Lipid-filled foom cells and T Iymphocyles O (E) Choleslerol c1efls sunuunded by proliferating smooth Ilmscle cells and foom cells

O lA) A history of diabetes mellitus O (8) Myxoid change and fragmenlation of eiaSlic lamellae in the aUI1ic media

O (C) Severe atherosclerosis of proximal aorta O (O) A pasl hislory of syphilis O (E) A congenital cardiac malformalion 20. A 4O-year..-old female has fever and a nonproductive cough of 6 weeks' duralion. A transbronchial biopsy reveals necroli:ting gmnulomatous inflammalion centered around small peripheml pulmonary artery brallches. labomlory findings include a urinalysis showing the presence of 50 red blood ceJls per high-power field along with red blood cell casts, a serum crealinine of level of 5.1 mg/dL, and a serum e-ANCA determination positive al a 1:512 tiler. Her underlying disease is tTlOst likely to be

O O O O O

(A) Polyarteritis llooosa (B) Pulmonary hypertellsion (e) Hyperplaslic arteriolosclerosis (O) Giant cell arterilis (E) Wegener gmnulomalosis

Courtesy of Tom Ro~'Crs. MD. Dcpartn~1l1 of rallllยกI"f:'Y. Unil'cr.ยกlly or Texas Soulhwcstem Medical School. l)alla<;. TX.

22. "be figure shows lhe microscopic appearance of lhe len. anterior descending artery found al aUlopsy of a 59year--old maleo Which 01' Ihe following laboratory lest findings is believed lO be etiologically related lo the process illustrated here?

O O O O O

(A) Low lipoprotein Lp(a) (B) Posili\'e VORL (e) Low HDL choleslerol (D) Elevaled plalelel count (E) Low plasma homocysleine

23. Afler a fall, a 59-year-old female experiences sorne righl hip pain. A mdiograph reveals no fraclures, bul lhere are calcified, medium-si7.ed arterial branches in Ihe region of Ihe pelvis. What is Ihe signilicallce of this fillding?

O O O O O

From lhe lCllChing colkdion of lhe Dcpartmcnl of rยกllhology. Unil'ersily of Tcxa~ Soulhwcstcm Medical School, Dalias. TX.

21. lhe gross appearance of Ihe aorta from a 12-year-old male who died of leukemia is shown here. Hislologic examination oC Ihe linear pale marking is mosl likely lo reveal

O (A) A corc oC lipid debris cO\'ered by a cap of smooth

(A) This is a feature of diabetes mellitus. (B) Her blood pressllre needs lO be checked. (e) This is an incidental finding. (O) She is at risk for gangrenous necrosis. (E) Hyperparalhyroidism is likely.

24. Por more than a decade, a 45-year-old male has had poorly controlled hypertension in lhe r,mge of 160195 mm Hg. Por Ihe pasl 3 months, his blood pressure has increased lo 250/125 mm Hg. He now has a serum crealinine level of 3.8 mg/dL. Which of lhe following va<ยกclllar lesions is mosl likely lo be found in Ihe kidneys?

O O O O O

(A) Hyperplastic arteriolosclerosis (B) Granulomalous arteritis (e) Fibromuscular dysplasia (O) Polyarteritis nooosa (E) I-Iyaline arteriolosclerosis

muscle cells

O (B) CollecliOll of foam cells. necrolic

area~, alld calcificalion O (C) A lipid t:ure, gmnulatioll lissue. and areas of hemorrhage

25. Afler a masteclomy wilh axillary nooe disseclion a year ago, a 47-year-old female has swelling and puffincss of her len ann that persisls all Ihe time. The underlying skin appears finn. The ยกum is nol painfuJ or discolored.


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She had .a 00u1 of cellulitis in this lefl aon 3 months ago. Her coodition is best called

BLOCO VESSELS

105

O (O) Blindlle.~~ O (E) Gangrene of lhe loes

O (A) ThrombopOlebitis O (B) Subdavian arterial thrombosis

O (q Tumor embolization

O (O) l),mphedema O (E) Vasculitis

For eactl of the descriplions of patients in questions 26 and 27, match lhe mosl dosel)' associated laboralory test fioding. (A) Anti-dooble-slranded-ONA liter of 1:512 (B) c-ANCA tiler of 1:256 (q Cryoglobulinemia (O) Plasma glucose level of 200 mg/dl (E) HBsAg posilive (f) Serum HOl choleSlerol of 10 lllg/dL (G) HIV posilive (H) HOlllocyslinuria (1) Serum lDL choleslerol of210 mgfdL (J) p-ANCA tilerof 1:128 (K) Plasma renin of 15 mg/mUh (l) Serologic test rOl" s)'philis posilive (M) Total sen.Lm ch6It$lerol of 140 mgldl 26. A 79-year-okl remale "'aS diagnosed with a progres. si\'e dementia. She wa-:; a nonsmoker, and she had a blood pressure of 90155 mm Hg. She is fouod al aUlops)' lO llave no cerebr,d alherosderosis, no coronary alherosclerosis, and only a few lipid streaks in the aorta. Her underlying cause of death is found lO be Alzheimer's disease. ( )

TI. A 55·year-old female was found lO have a blood pressure of 16CVIOS mm Hg on several occasions in lhe pasI 3 mOlllhs. She feels fine and has hOO no major medical conditiolls during her lifetime. An abdominal ultrasound sean reveals Ih¡lt lhe len kidne)' is smaller lhan lhe right. An angiogr'<llll reveals a focal stenosis of the left renal anery. ( ) 28. In which of lhe following localions would you lel~r expecI lO find significant alherosclerOlic lesions in a palienl wilh risk faclors of smoking, hypenension, diabeles melliluS, and serum cholesterol rever of 280 mgldl?

O O O O O

(A) (B) (C) (O) (E)

Len main coronary artery Aortic bifurcation Circle of Willis Pulmonary artery lrunk Common carotid artery

29. A 75-year-old male has had headaches foc se,'eral months. On ph)'sical examination, he has a prominenl palpable nghl lemporal anery Ihal is painful lo touctl. The biopsied segmenl of thickened lemporal artery shows focal granulomalous inf1anunalion. This condition responds well to cOfticosleroid merapy. Which of Ihe following complicalions is masl likely in untreated patients? O (A) Renal failure O (B) Hemoplysis O (C) Malignanl hypertension

30. A 30-year-old female who has smoked cigareues since she W'dS a lee.nager has painful Ihromboses of lhe superficial veins of her lower legs for a monlh. 1ben she expenences episodes when her fingers become blue aOO cold. Over lhe next year, she develops chronic, poorfy healing u/cerdtions of her feel. One toe becomes gang.renous and is amputaled. Hislologically, al Ihe resection margin lhere is an acute and chronic vasculitis involving medium-sized artenes wilh segmemal invol"ement. She is best advised Ihm

O (A) Hemodialysis is nceessary O (B) O (C) O (D) O (E)

She musl slop smoking Corticosteroid Iherapy will be effeL1ive Antibiolic lherapy for syphilis is required Insulill thempy can conlrol Ihis disease

31. A 40-year-old maJe has experienced malaise, fever, and a 4-kg weighl loss over the pasl Inol'llh. He is found lO have a serum urea nilrogen cOllcentrn.lion of 58 mg/dl and a serum crealinine level of 6.7 mg/dL. Renal angiography reveals righl renal anerial thrombos.is. aOO lhe left renal artery and brnnches show segmental lUlllinal narrowing along with focal aneurysmal dilalion. While receiving hemodial)'slS a week later, he is found lO have melena in a~~ialion wilh abdominal pain aOO dianhea. Which of the following laboralory test findings is IIlO6I likely?

O (A) Positi"e e-ANCA O (B) Positive antinuclear antibody (ANA) O (e) Positi\'e HIV O (O) Positive hepalitis B surface anligen O (E) Positive ScI-70 32. A 30-year-old. overweighl remOlle is a school leacher who is kllown to be a Slricl disciplinari:m in Ihe c1assroom. She presems wilh angina pecloris, and coronary 3ngiogmphy reveals 75% narrowing of Ihe anterior descending branch of Ihe len coronary artery. Which of the following would be a major risk faclor for coronary atherosclerosis in this palient?

O (A) Obesity O (B) Type A personalily

O (C) Diabeles mellitus O (O) Sedentary life style O (E) Ag. 33. Several skin lesions on !he upper chest of a 45-yearold male have cenlral pulsatile cores. Pressing on a core causes a radialJy arranged array of subctJtaneous arterioles lo blanch. The size of the lesions fmm core lo periphery is 0.5 lo 1.5 cm. lbe underlying disease he is most likely lo !\ave in associalion with lhese skin lesions is

O (A) Wegener grdnulomalosis O (B) Micronodular cirrhosis O (C) Marfan syndrome O (D) Acquired irnmunodeficiency syndrome O (E) Diabeles mellitus


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DISEASES QF ORGAN SYSTEMS

34.

Itehing with burning pain in Ihe perianal regioll 1Il a female has been presenl for several monlhs. Physical examinalion reveals dilaled and thrumbosed exlernal hemorrhoids. Whal underlying process most likely led lo her pre~nt eondition? 22~year-old

O O O O

(A) Rectal adenocarcinoma (B) Pregnancy (e) Polyarteritis nodosa (O) Filariasis O (E) Micronodular cirrhosis

ANSWERS l. (A) Atheromalous plaques can be complicaled by a varielY of palhologic alteralions. including hemorrhage. ulceralion. thrombosis, and cakificalion. '111ese processes can inerease Ihe size of the plaque and narrow the residual arterial lumen. Although alherosclerosis is a disease of ¡he inlima. the media is eompressed by Ihe expanding plaque wilh advanced disease. This causes Ihinning of the media. which weakens the wall and predisposes lO aneurysm formalion. BP6 285 - 288 PBD6 507 - 509 2. (8) 'Iñis arleriole shows marked hyaline Ihiekening of the wall, indicalive of hyaline arteriolosclerosis. Diabeles mertilus can also lead to mis finding. Sepsis can produce DIC with arteriolar hyaline Ihrombi. 'nle debililation thm aceompanies caneer lends lo diminish vascular disease due to atherosclerosis. Syphilis can cause a va<¡culilis involving the vasa vasorum of Ihe aorta. Polyarterilis can involve lurge lo medium-sized arteries in many organs, including kidneys. 'rhe affecled vessels show fibrinoid necrosis and inflammation of the wall (i.e.. vasculilis). BP6292-293 PBD6514-515 3. (D) Abdominal aneurysms are mosl frequently related lO underlying atherosclerosis. This patient has multiple risk factors for alherosclerosis, including diabetes mellitus, hyperlension, and smoking. When lhe aneurysl11 reaches this siu~. Ihere is a significant risk for ruplure. BP6 299 PBD6 525 - 526 4. (1) Henoch-Schonlein purpura is the multisystemie eounterparl in children of IgA nephropalhy seen in adull~. The immune complexes fornled with IgA produce Ihe vaseulilis Ihal affects mainly arterioles. capillaries. and venules in skin, gastroinleslinal Iracl, and kidney. BP6453 PBD6 517, 961, 965 5. (O) Wegener gmnulomalosis is eharaclerized by necrolizing granlllomatous infiammalion Ihat Iypically involves Ihe upper respiralory lracl. small lo medium-sized vesseJs. and glomeruli. The lungs are often involved. although other organ siles may also be affeeted. It is a type 01' hypersensilivilY reaelion lO an unknown antigen. BP6295-296 PBD6522-523

6. (A) The lowering of eholeslerol. parlieularly Ihe LOL choleslerol wilh Ihe same or increa"ed HOL cholesterol level. indicales a lowered risk for alherosderotic eomplieations. Alhemsclerosis is mllltifaclorial, bul modificalíon of diet (i.e .• reduction in total dielllry fat and cholesterol) with increased exercise is the best way of reducing risk for most persons. Glucose is a mellsure of eonlrol 01' diabetes mellitus. POlassium, calcium, lllld renin values may be altered wilh sorne fOlms of hypertensioll. one of Ihe risk faClOrs for alherosderosis. BP6283-284 PBD6504-506 7. (D) This is eyslic medial necrosis, which weakens me aortic media and predisposes lo aortic disseclion. In a young patient, such as Ihis one, a heritable disonier of conneclive lissues such as Marfan syndrome musl be slrongly suspccted. Alherosclerosis with diabeles mellilus and hypertension are risk factors for aorlie dissection. a1though al an older age. Sclerodenna and Wegener granulomatosis do nol typically involve Ihe aorta. BP6 301 PBD6 526-528 8. (C) He hllS an alherosclerolic abdominal aortie aneurysm. Diabeles mellitus is an importanl risk faclor for atl1erosclerosis and musl be SUSpecled if a young malc or premenopausal female presents with severe atherosclerosis. Polyarleritis nodosa does nol Iypieally involve Ihe aorta. Obesily is a "soft·· risk factor for atherosclerosis. SLE pnx1uces small arteriolar vasculilis. Syphililic aortilis invol ves Ihe ¡hofllcic aorla. BP6299 PBD6525-526 9_ (E) Thcse dilaled. endothelium-lined spaees are filled wilh red blood cells. Tite circumseribed nalUre of Ihis lesion and ils long. unchanged COUfSC suggest its benign nalllre. Kaposi sarcoma is uncommon in its endemie foml in childhcxxl, and il is besl known llS a neoplastic complicalion associaled with HIV infeetion. Angiosarcomas are large. rapidly growing malignancies in adults. Lymphangioma" tend lo be more dilTuse and are nol blood filled. bUI they are 1I10s1 often seen in children. A lelangieetasia is a radial array of subculaneous di laled al1eries 01' arterioles around a central core, and il may pulsate. BP6304-305 PBD6532-533

10. lt\) Atherosderosis is considered a complex reparative response Ihal follows endothelial eell injury. HypercholeSlerolemia (i.e., high LDL cholesterol leve!) is believed lO cause sublle endolhelial injury. 'Ibe oxidation of LDL by maerophages or endothelial certs hllS many deleterious effeclS. It is chemotactic for circulating monocyles. causes monocyles lO adhere to endothelium. slimulales relea~e of growlh faelors and cytokines. and is cytoloxic lo smoolh muscle cells and endolhelium. Smoolh muscle pro-liferation in response lO injury is important in Ihe dcvelopment uf atheroma... This is driven by growth factors, indllding PDGF. HOL is believed lo mobili:t,.e choleslerol from developing alheromas and hence high HDL levels are proleclive. ICAM-I and VCAM-I are adhesion moleeules on endolhelial eells Ihal promote adhesion of monocyles to the site of endolhelial injury. BP6285-286 PBD6507-509


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Chapler 11

1l. (E) These findings are mosl suggestive of syphililic aortitis, a complicalion of lertiary syphilis. wilh characteristic involvemelll of Ihe lhoracic aorla. Oblitemtive endarteritis is nol a fealure of other fomlS of vasculilis. High-liter double-stranded ONA antibodies are diagnoslic of SLE, and the test resull fOI" p.-ANCA is positive in various vas· culilides, induding microscopic polyangiilis. A high sedimenlalion rute is a nonspecific markel" of inflammalory diseases. Kelonuria may occur in persons wilh diabetic ketoacidosis. BP6299-300 PBD6526 12. (C) This is a common problem thal results from ve· nous slasis. There is litlle or no inflammation, but Ihe lerm is well established. Lymphedema takes longer lO develop and is nol callsed by bed resl alone. OIC more often reSlllts in hemorrhage, and edema is not the most prominenl manifestalion. Thromboangiilis obliterans is a mre fonn of arlerilis thal results in pain and lllceration of exlremities. Varicose veins are superficial and can thrombose, bU! they ¡lre nol relaled lO bed res!. BP6302-303 PBD6530 13. (8) This palienl has essential hypertension (Le., no obvious cause for his moderale degree of hypenension). Renal relelllion oC excess sodium is thoughl to be impor~ lant in initiating Ihis fOl1n of hyperlension. This leads to an increased intmvascular fluid volume, increase in cardiac outpul, and peripherul vasoconstnclion. Increased cateeholamine secl"etion (as may occur in pheochromocyloma), gene defecls in aldoslerone melabolism. and renal artery stenosis can all cause secondary hyperlension. However, secondary hypenension fmm aH causes is much less common than eS5ential hypertension. Increased production of atrial natriuretic faclor reduces sodium retention and Iherefore reduces blood volume. BP6290-291 PBD6512-513 14. ro) Alherogenesis can be considered a chronie inflammalory response of Ihe arterial wall lO endOlhelial injury. The injllry pmmoles participation by monocytes, macrophages, and T Iymphocytes. Smoolh mllscle cells are stimulated lo proliferute. Plalelets adhere lO areas of endoIhelial injury. However, neutrophils are nol a part of atherogenesis. allhough Ihey may be seen in various forms of vasculilis. BP6 285-287 PBD6 507 -509

15. (A) Alherosclemsis is lJelieved lO result from some fmm of endolhelial injury and the subsequent chronic inflammation and repail" of Ihe imima. AII risk faclors, induding smoking, hyperlipidemia, and hyperlension. cause biochemical 01" mechanical injury lO Ihe endolhelium. For~ mation of foam cells oceurs afler Ihe inilial endOlhelial injllry. Lipoprolein receplor alterations may occur in sorne inherited condilions, bul Ihese conditions accOUIll for only a fmclion of cases of alherosclerosis, and other lifeslyle condilions do nol affeel their aclion. Inhibilion of LOL oxidation should diminish athemma formalion. Vasomolor tone does nol playa major role in atherogenesis. BP6284-286 PBD6505-508

BlOOD VESSELS

107

16. (A) The venous slasis reSlllts in hemosiderin deposition and derrnal fibrosis wilh brownish discoloration and skin roughening. Focal ulceralion may occur over lhe varicosilies, but exlensive gangrene similar lo whal occurs wilh arterial alhel"osderosis does not occur. The varicosities involve just Ihe superficial set of veins, which may thrombose, bu! are nol the source of Ihromboemboli, as are the larger deep leg veins. The thromboses in superficial leg veins do nol lead to Ole. 'Ibe varicosities do nol affeel muscle, allhough lack of muscular support for veins lo ··squeeze" blood OUI fOl" venous relurn may predispose lo formalion of varicose veins. BP6 302 PBD6 529 17. (A) Human herpesvirus 8 has been associaled with Kaposi sarcoma and can be acquired as a sexually lrans~ miued disease. Kaposi sarcoma is a complication of ac· (juired immunodeficiency syndrome (AIOS). Persons with HIV infection can be infected with a variely of viruses. including EBV and CMV, bul Ihese have no etiologic a<;sociation with Kaposi sarcoma. EBV is a faclor in Ihe developmenl of non-H<X.lgkin Iymphoma, and CMV can cause colitis or relinitis or may be disseminated. HBV can be seen in HIV-infected palienls as well, particularly Ihose wilh a risk factor of injection drug use. Adenovirus can be seen in HIV-infecled persons. allhough not frequently; il lends lo be a respiratory or gastrointestinal infeclion. BP6305-307 PBD6535-536 18. (D) Aneurysms. including aortic aneurysms, form in areas of weakness of an arlerial wall. Abdominal aorlie aneuryslTls are typically atherosclerotic in origino Alherosderolic plaques comprcss Ihe media. and Ihis can cause alrophy of the media. Beeause Ihe media provides elasticity and support lO Ihe vessel wall. weakening of Ihe media predisposes lO aneurysmal dilatalion. Ulceration, Ihrombo-siso and hemorrhage occm superficially in atheromatous plaques and tend lo promote narrowing of arterial lumens. nol arterial dilalion. Cystic medial necrosis is a fealure of Marfan syndrome. BP6 299 PBD6525-526 19. (8) He has an aortic dissection in which Ihere has been an intimal lear Ihal allows bl<xXI lo disscel into lhe aortic media. The dissection in Ihis patienl extended lo Ihe greal vessels lo cause lamponade as evidenced by diminished upper exlremity pulses. The most frequenl preexisting hislologically deleclable lesion in lhese cases is cyslie me~ dial degeneration (CMO), also known as cyslic medial necrosis. Some cases of CMO are associated wilh Manan syndrome. Hypertension and atherosc1erosis are additional risk factors thal can be idenlified in palienls with aOl1ic disseclion. Syphilitic aortitis can lead lo ischemic aortic medial injury lhal results in aorlie arch dilation with Ihe polenlial for rupture. bul such cases are far less frequenl than aorlic dissection from CMO. BP6300-302 PBD6526-528 20. (E) Puhnonary and renal involvemenl can be serious and Iife-Ihrealening wilh Wegener granulomalosis. Polyarlelitis is less Iikely to involve the lungs, and the inflammalion is nol typically granulomatous. p-ANCA 01" c4ANCA


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Pa" 2

DISEASES O, ORGAN SYSTEMS

are absent in polyarteritis. Pulmonary vascular hypertensive changes include vascular thickening and lortuosity, alIhough nol usually innammation. Hyperplastic arleriolosclerosis is a lesion mosl Iypically ~n with malignant hyperlension in systemic circulation. Cianl cell arteritis is mosl typical for lempoml arteries and branches of lhe external carolid mteries. BP6295-296 PBD6 522-523 21. (D) 1l1ese slighlly raised, pale lesiOIlS, called ralty streaks, are seen in Ihe aorta of almost all children older Ihan 10 years. 'nley are Ihoughl to be precursors of alheromalous plaques. Fally streak.s cause no diSlurbances in blood now amI are discovered incidentaliy al aUlopsy. AII the olher lesiolls descríbed are seen in fully developed alheromalous plaques. The histologic features of such plaques indude a central core of lipid debris that may have choleSlerol c1efl~ and may be ca1cified. There is usually an overlying cap of smoolh muscle cells. Hemorrhage is a complicalion seen in advanced atherosclerosis. Foam cells, derived fram smoolh muscle cells or macrophages that have ingesled lipid. can be presenl in aJl phases of alherogenesis. BP6286-289 P8D6 502-503 22. (e) 1l1e arlerial lumen is markedly na/Towed by alheromalous plaque complicaled by ca1cilicalion. Hypercholesterolemia wilh elevaled LOL and decl"eased HOL levels is a key risk factor for atherogenesis. Syphilis (i.e., positive VORL test resull) produces endarteritis oblilerans of aortic vasa va<;orum. 'l1lis weakens Ihe waJl and predisposes lo aneurysms. Although platelets participate in fomling alher4 omatous plaques. their numbel" is not of majol" imlxlItance. Thrombocylosis can result in Ihrombosis or hemorrhage. I..evels of Lp(a) and homocysteine. if elevaled, increase the risk for atherosclerosis. BP6287-289 PBD6504-506 23. (C) Older adulls with ca1cified anenes oflen have Monckeberg medial calcilic sclerosis, a benign process Ihal is one form uf arteriosclerosis wilhoul serious sequelae. Such ca1cification of arteries is far less likely to be a consequencc of atherosclerosis wilh diabetes 01" with hypercalcemia. Hypertension is mosl likely to affeel small renal artenes, and calcilication is nol a major fealure, ahhough hypenension is also a risk factor for atheroscle· rosis. BP6 283 PBD6 498 24. (Al This palienl has malignant hypertension superimposed on benign essential hypertension. Malignanl hyperlension can suddenly complicate hypertension of a lesser severity. The arterioles undergo concenlric Ihickening and luminal narrowing. A granulomatous arlerilis is mosl characlerislic for Wegener granulomalosis, which often involves Ihe kidney. Fibromuscular dysplasia involves Ihe main renal arteries and can lead lo hypertension but not Iypically malignant hypertension. Polyarteritis nodos<, produces a vasculilis [hat may involve Ihe kidney. Hyaline arleriolosderosis is seen with long-slanding essenlial hyperlension of moderate degree. These lesions give rise lo benign nephrosclerosis. The affecled kidneys become sym-

metrically shrunken and granular because of progressive loss of renal parenchyma and consequenl fine scarring. BP6292-293 PBD6 514-515 25. (D) The mastectomy wilh axillary Iymph node disseclion leads lo disruption and obstruction of Iymphalics in Ihe axilla. Such obsllUclion lo flow of Iymph gives rise lo lymphedema. a condition that can be complicated by cellulilis. Thrombophlebilis from venous stasis is more commonly a complicalion seen in the lower extremilies. An arterial throlllhosis can lead lo a cold, blue, painful exlrelllity. Tumor elllboli are generally slllall: they are uncomlllon. Va<;culilis is not a complication of surgery. BP6303 PBD6530-531 26. (M) Hypercholeslerolelllia is a major driving force behind alherogenesis. A total cholesterol level of less Ihan 200 IllgldL carries a low risk fOr development of complicalions of alherosclerosis, and c1inical events resulting from alherosclerosis are uncommon when Ihe total cholesterol cOllcenlralion is below 150 mgldL. It is beUer lo llave more HOL cholesterol Ihan more LOL cholesterol. BP6284-286 PBD6504-506 27. (K) 'nlis is a dassic example of a secondary form of hypertension in which a cause can be determined. In Ihis case, lhe renal arlery stenosis reduces glomerular blood now and reduced pressure in Ihe afferent arreriole, resulling in renin release by juxlaglomerular cells. '111e renin iniliates angiolensin II-induced vasoconstriclion, increased peripheral vascular resistance, and increased aldoslerone Ihal promotes scxlium reabsorption in the kidney, resulling in increased blood volume. BP6290-291 PBD6 512-514 28. tD) 1l1e pulmonary vasculalure is under much lower pressure Ihan the syslemic arterial circulalÍon and is much less likely to have elldothelial damage that promoles atherogenesis. Alherosclerosis is more likely lo occur where blood now is more lurbulenl, and this occurs af arlerial branch poinls and in Ihe first few centimeters of the coronary arteries. BP6284-285 PBD6 507-508 29. (1) 'l1lis palienl has c1inical fealures suggesting gianl cell (tempoml) arleritis. This form of arterilis Iypically involves large lO medium-sized arleríes in Ihe head-especially temporal arteries-bul also vertebral and ophlhalmic arteries. The lalter can lead lo blindness. Because involvemenl of the kidney, lung, and peripheral arteries of the exlremities is much less common, renal failure, hemoplysis, and gangrene of toes are unusua!. There is no associalion with hypertension. BP6297 PBD6 517-518

30. (B) She has features of thromboangiitis oblilerans (i.e., Buerger disease). This disease. which affecl<; small lO medium-sized arteries of the exlremities, is slrongly associaled wilh smoking, Renal involvement does not occur. Immunosuppressive Iherapy is nol highly effeclive. Syphilis produces an aortitis. Although peripheral va~cular disease


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Chapter 11

with atherosclerosis is typical for- diabetes mellitus, v3SCulilis is not

BP629B-299 PBD6 523 31. (O) Segmenlal invoJvemenl of medium-sized arteries with aneurysmal dilalion in renal vascular bed aOO ¡:>resumed mesenteric vasculitis (e.g., abdominal paill, melena) is most likely caused by polyanerilis lIodosa. Polyarteritis can affect many organs at dífferenl times. A1though !he cause oC polyarterilis is unknown, aboul 30% oC palients have hepatitis B surface anligen in serum. Presumably, hepatitis B surface anligen-antibody complexes damage lhe ves,<;el waU. Unlike lhe situation with microscopic polyangiitis, lhere is no known associalion with ANCA Vasculitis with HIV infeclion is uocommoll. A collagen vascular disease with a positive ANA resull, such as SLE, may produce a vasculitis but not in lhe p.,ttem seen here. 1ñe affected vessels are smaller. The ScI-70 autoontibody is indicative oC sderoclenna, which may produce renal failure.

BlOOD VESSELS

109

33. (O) These lesions are spider telangiectasias, which are a fealure of micronoduJar cintlOsis, lypicaUy as a consequence of chronic akoholism. Spider leJangiectasias are lhoughl to be caused by hyperestrinism (i.e., estrogen excess) Ihal resullS from hepatic damage. Vasculilis lend.s nof. lo produce skin telangiectasias. 1be vascular involvemenl in Marfan syndrome is primarily in the aortic arch wilh cyslK:: medical necrosis. The mosl common vascular lesioo of skin with AIDS is Ka¡x>si's sarcoma, which is a neoplasm presenting as one or more inegular, red lO purple palches, plaques, or nodules. Diabetes rnellitus, with acceleraled atherosclerosis, is most likely to result in ischemia or gangrene.

BP6 304 PBD6 534

32. (C) Diabetes mellitus is a significant risk factor for early. accelerated, aOO oovanced 3lherosclerosis. If a premenopausal female or a young ma1e presenlS wilh severe comoary atherosclerosis, diabetes must be suspected as a predisposing factor-. "Soft" risk faclors Ihat play a lesser role io developmenl of atherosclerosis may include obesity, stress, and ¡ack of exercise.

34. (B) The hemorrhoidal veins can become dihlted fmm venous congestiono This is most common with chronic conslipation, bul Ihe pregnanl ulerus presses on pelvic veins lo produce similar congestion that pl"Olllotes hemorrhoidal vein dilalion. Carcinomas are nol likely lo obslrucl venous now. I'olyarteritis does nol affcct veins. Filarial infeetions may afreel Iymphatics, induding lhose in lhe inguinal region, and produce Iymphedema. Portal hypel1ension wilh cirrhosis is mosl likely lO dilate submucosal esophageal veins, bul hemorrhoidal \'eins occasiooally may be affccted. However. cirrhos:is would be rore al her age.

BP6 264 PBD6 504-506

BP6 302 PBD6 530

BP6293-295 PBD6520


CHAPTER

12 The Heart BP6 Chapter 11 - The Heart PBD6 Chapter 13 - The Heart

1. A 50-year-old male experiences episodes af severe substemal ches! pain every time he perf~ms any lask requiriog moderale exercise. These episodes ha\'e become more frequent and severe in lhe past year. bol they can be relie\'ed by use af sublingual nitroglycerin. Which of lhe following cardiac I~ions ¡s probably present?

mies O\'er bolh of the lungs, 1l1e patient wa., admiued to the hospital, Ouring the hospilHl stay, he had several epi~ sodes of alrial fibrillation, and he developed signs of acute leO venlricular failure and died of pulmonary edema 2 days after admission. Which of the following changes is least Iikely to be seen in lhe heart?

O (A) FibrinOlls pericarditis O (O) Aschoff nodules in the myocardium O (e) Fibrosis of milml valve wilh fusion of commis-

'"res

O (D) Foci of fibrinoid necrosis in milral valve

O (E) Dilatation of the left \<entricle

O (A) Rheumalic ITÚtral stenosis O (8) Serous pericarditis

O (C) Restriclive cardiornyopathy O (O) Calcific aortic stenosis O (E) Atherosclerotic narrowing of coronal)' arteries

2. Ten years after rtteiving an aonic valve bioprosthesis because of infeclive endocarditis. a 44-year-old female ¡s mosl likely lO suffer which uf ¡he folluwing complicalions'!

o (A)

Pllrllvalvular leak O (O) Slenasis O (e) Hemolysis (O) Embolizalion (E) Myocardial ¡n"arclion (MI)

o o

3. lbc direction af blood now and lhe c\inical severity of symptorns in telralogy of Fallot is delermined primarily by !he

O (A) Size of the lert ventricle O (8) De~ of pulmonary stenosis O (e) Size of lhe ventricular seplal defttl (VSO) O (O) Oia.meler of the lricuspid valve O (E) I'resence of an alrial seplal defttt (ASO) 4. A 12-year-old male presented with a sore throal and fever. 'n,roat culture was posilive for {3--hemolYlic SlreploCncCIU'. '1l1ree weeks later. lhe sore throal hOO resolved, bul lhe pmienl developed a reddish rash, On examinalion, lhe pcdiatrician noticed a murmur of mitral regurgitalÍoll and

110

Counay of Al1hur Weinber1l. M.O. Ot'parrrrc~ or PalhokJgy. Univt'fSiI)' <Jf Tt'1US Soulh"'t9l'm ~tedical Schoot, Oall~ TX.

5. 1ñe gross appearance of lhe hean of a 5-year-old child al aulopsy is illustraled here. Which of lhe following addilional palhologic condilions would yoo most likely find?

O (A) Chmoic renal failure

O (O) Coronar)' alherosclerosis O (e) Thyrnic hypoplasia 0(1) Pulmonary hypertension O (E) Dilated cardiomyopathy


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Chopter 12

THE HEART

111

O O O O

(A) EJevated anti-streptolysin G titer (13) Positive antineulruphil cytoplasmic autoantibody (e) Increaserl creatine kinase MB fraction (O) I-ligh double-slmnded DNA autoantibody titer O (E) POS;I;,. blood C"'l"" roc Stap",'lococcu' m..." " 8. A young patient presents with chronic progressivc ex~ ercisc intolerance. TIle electrocardiographic resull<; and radiologic evidence suggest severe left ventricular hypertrophy with a prominent septum. The right ventricle is also somewhat thickened. The anterior leallet of the mitral valve moves inlo the outnow traet of the len ventricle during systole. Hemodynamic lests reveal an abnormally higb ejection Fraction bul low ventricular volume and low cardiac output. The most likely cause of cardiac abnormalities in Ihis palienl is

6. The gross appearance of the hearl of a 68-year-old male at autopsy is shown here. The mosl likely complicalion resuhing from this lesion is O O O O O

(A) Cardiac rupture (13) Acute pericarditis (C) Systemic thromboembolism (O) Cardiogenic shock (E) Constrictive pericarditis

O O O O O

(A) Mulations in {3-myosin heavy chain (13) Autoimmunily against myocardial tibers (e) Chnmic a\coholism (D) Deposilion oF amyloid protein (E) Lmellt enlerovirus inl'ection

9. Infeclion with which ol' the Following organisms is most likely to give rise to a bloody pericardial efl'usion with a high prolein conlenl? O (A) O (13) O (e) O (O) O (E)

MycolxlcleriulII IIIberclIlusis Group A Slreplococc/lS

Coxsackievirus B Cal/dida albicans S. OII,.ell.~

10. A young injection drug user presents with rever. a new munnur. and menlal slatus changes. 13100d cultures are positive for S. anreus. and her white blood cell counl is 19.2001p-L. An echocardiogram reveals a 1.5-cm vegelation 011 the mitral val ve. Which of Ihe changes lisled is leasl likely to be a complication oF her disease process'! O O O O O

7. TIle gmss appearance of the heart depicted in the fig~ ure here was seen at aUlopsy of a 25-year-old male who died after an illness of less than 3 days' duration. Which of the following laboratol), test findings was pmbably obtained during his hospital course on the day before he died?

(A) Left atrial dilalion (B) Glomerulonephritis (e) Intramyocardial or ring abscesses (O) Celllral nervous syslem embolic evento;; (E) Myxomalous degeneration of the mitml valve

11. A 19-year-old male has had a low-grade fever for 3 weeks. Gn physical examinalion, he has a temperalure of 38.3 c C. with a respiration rale of 28, pulse of 104, and blood pressure of 95/60 mm Hg. A lender spleen lip is palpable. Splinter hemorrhages are observed on his fingernails. A hem1 murmur is auscultated. Which of the following infectious agel1ls beSI accounts for these findings?

O

(A) SlrcJJ/ocoCCIIS I'iridlllls

O (B) Try/x!l/osuma crtlzi O (e) Coxsackievirus B

O (O) C. albicans O (E) M. fIlberCII/osis


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'112

Parf 2

AIIR " p o _

! >

DISEASES OF ORGAN SYSTEMS

12. A Ihrombolic ocdusion of lhe left circumllex artery occurs in a 50-year-old male with severe coronary alhero-sderosis, Wilhin an hour afler the Ihrombus forms, which of Ihe fo\lowing complicalions is mosl likely lO occur?

O O O O O

(A) (B) (C) (D) (E)

Venlricular fibrillation Pericarditis Myocardial rupture Ventricular aneurysm 1l1mmboembolism

For each of lhe palienl histories in queslions 13 through 16. malch the mosl c10sely associaled descriplion of a cardiovascular disease process: (A) Congenilally stenotic pulmonic valve a~socialed wilh a VSD (B) Dilation of Ihe a0l1ic valve ring with an aneurysm of lhe arch of aorta (C) Fibrinoid necrosis of medium-si .....ed arleries in many organs (D) Fibrolic mitral valve associated wilh thickening and fusion of lhe chordae telldilleae (E) Fr.lgmelltation of elaslic fibers in the media of Ihe aortic arch (F) Granulomatous innammation and fibrosis of Ihe media of the aortic arch with narrowillg of aortic lumen (G) Heavily calcified aortic valve wilh Ihree cusps (H) Heavily calcified, congenitally bicuspid aortic valve (1) "H<XX1ing" deformily and myxomatous degeneration of Ihe mitral valve (1) Large, deslruclive vegelalions involving lhe aortic valve (K) Small, nondeslruclive vegetations on an otherwise normal milraJ vaJve 13. A 30-year-old African-American male with longstanding essenlial hypertension collapses after the sudden onset of severe chest pain. On physical examination. his radial pulses are weak but femoral pulses are normal. A chest radiograph reveals widening of the mediaslinum. ( ) 14. A 35-year-old asymptomalic femaJe is found to have a mid-syslolic c1ick heart mum1Ur during a routine physical examination for an insurance policy. ( I

hearl shadow. Which of Ihe following condilions probably loo to Ihese findings.

O (A) Cenlrilobular emphysema O (B) Hypertension

O (C) Tricuspid valve regurgitation O (O) Chronic alcoholism O (E) Silicosis 18. Al autopsy. Ihe hearl of a 73-year-old male shows marked right ventricular and righl atrial dilation and hyper~ trophy. The aorta shows minimal alherosclerosis, and Ihe pulmonary lrunk shows moderale alheroselerosis. Which of the following condilions is mosl likely to have given tise to Ihese findings?

O (A) O (13) O (C) O (O) O (E)

Saddle pulfnonary Ihromboembolism Ventricular septal defect (VSO) Chronic obslructive pulmonary disease Rheumalic heart disease (RHO) Hypertrophic cardiomyopalhy

19. A 34-year-old female with no history of heart disease has had palpitalions. faligue. and chest pain worsening for Ihe past year. Auseultalion of lhe chest reveals a midsystolic c1ick. What are the resulls of an echocardiogram most likely lo show?

O (A) A0l1ic valvular vegelatiolls O fll) Pulmonic Slenosis O (C) Mitral valve prolapse O (O) Patent duCluS arteriosus (PDA) O (E) Tricuspid valve regurgilalion 20. A 15-year-old female jumps up lor a block in the third match of a volleyball tournament. She collapses and cannot be revived despite cardiopulmonary resuseitation. She had been healthy all her life and complained only of sorne limiled episodes of chest pain during games in the currenl sehool year. Which of Ihe following palhologic findings of the hearl is lhe medical examiner most likely lO find?

O (A) Haphazardly arranged. hypenrophied septal myo-cytes

O (B) Extensive myocardial hemosiderin deposition O (C) Tachyzoiles wilhin ("oci of myocardial necrosis and

15. A 50-year-old male with a history of a mucin-producing adellocarcinoma of Ihe pancrea~ dies after a 6-monlh course complicated by wasting. bronchopneumonia, and stroke. ( )

O (O) Mitral valvular stenosis with len atrial enlargement O (E) Large. friable vegelalions with destructiOIl of aortic

16. A 35-year-old male with a history of inlravenous drug abuse is brought to the hospital emergency room for evalualion of acute onset fever and altered mental status. A head cr sean reveals evidence of a righl parietal. 3-cm abscess. (

21. The gross appearallce of the heart in the following figure from a 59-year-old maJe with a hislory of an increa<¡ing renal failure is most characleristic for which of Ihe following underlying condilions?

17. A 68-year-old male presents with progressive dyspnea, experienced over the past year. By echocardiography, the len ventricular wall is greatly hypertrophied. His chesl radiograph reveals pulmollary edema and a prominent left

innammalion

valve cusps

O (A) Chmnic akoholism O (B) Hypenension O (C) Pneumoconiosis O (O) Hemochromalosis O (E) Diabetes mcllitus


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113

O (E) A second acule MI most Iike!y occurred on day 6

or 7. because myocardial ruplure usually occurs within several hours of the deve!opment of a transmural MI. 24. A 45-year--old male experiences crushing substernal chesl pain on arriving al work in Ihe morning. Over Ihe next few hours lhe pain persisls and begins to radiale lO his left armo He becomes diaphorelic and short of brealh, but he wails until Ihe end of his 8-hour shifi to go lO Ihe hospital. Which of ¡he following serum laboratory lesl find+ ings is most useful lO diagnose his condition on admission lo Ihe hospital?

O (A) Elevated lipase O (E) Elevated aspartate aminotransferase (AS'!)

O (C) Elevaled CK-MB O (O) Elevaled alanine aminotransferase (ALl) O (E) Elevaled lactate dehydrogenase type l (LOH-I) 22. A 4~year-old child is less lhml the 5l.h percentile for heighL and weighl for age. She is cyanoúc mld has no exercise tolerance. Arlerial blood gas measuremenl shows decreased oxygen salUralion. She now presenls wilh fever and obtund.1tion. and a cerebral cr sean shows a righL parietal. ring-enhancing, 3-cm lesion. She is most likely lo have which of Ihe following congenilal heart diseases?

o (A) O O O O

(8) (e) (O) (E)

Tetralogy of FallOI Arterial seplal defect (ASO) Patenl ducluS arteriosus (POA) Coarclalion of Lhe aorta Bicuspid aortic valve

23_ A 50-year-old male wilh a hislory of long-standing diabeles mellitus and hypertension developed pain in the lefi shoulder and armo He altributed the pain lo arthritis and took somc acelaminophen. Over Ihe nexl several hours. lhe palienl developed shortness of breath, which persisled over the nexl seveml days. On the third day, he visiled a doctor, who ordered detenllinalions of creatine kinase (CK) and troponin I levels. The lotal CK aClivity was wilhin reference range. bul the lroponin leve! was e!evaled. He was admilted lO the hospilal. where he conlinued lo experience dyspnea over the nexl 3 days. One day laler (7 days afler Lhe onsel of shoulder pain), Lhe patient suffered from cardiac arresl. Attempted resuscilation was unsuccessful. Postmorlem examinalion reveals a large Iransmllral myocardial infarcl (Ml) wilh ruplure of Lhe heart and acule hemopericardium. Which of Ihe following slalements is supported by the c1inical and aUlopsy data?

25. A 60-year-old male diabelic has experienced angina on exerlion for several years. A previous coronary angiog+ raphy revealed 75% slenosis of the left anterior descending coronary arlery and 50% Slenosis of Ihe right coronary anery. His blocxi pressure is 110/80 mm Hg. In Ihe pasl few weeks, the frequency and severilY of his anginal atlacks have increased, and sometimes Ihe pain occurs even when he is Iying in bed. The most likely explanalion for these changes in his symploms is

O (A) Hypertrophy of the ischemic myocardium wilh increased oxygen demands 0(8) Increasing stenosis of Ihe tighl coronary artery O (C) r:issuring of Ihe plaque in left coronary arlery with superimposed mural (partial) thrombosis O (D) Sudden complele thrombolic occlusion of Ihe riglll and leh coronary arleries O (E) Reduclion in oxygen-carrying capacily fram puhnonary congeslion

O (A) The palienl InoSI probably did not deve!op MI until day 5 or 6 after Ihe episode of cheSl pain.

O (B) The normal CK leve! oblained on day 3 excllldes Ihe possibility of MI in the preceding 72 hours.

O (e) The normal CK leve! and elevaled Iroponin leve! oblained on day 3 are consiSlent wi¡h an acule MI occurring on Lhe day lhe palienl developed shoulder pain. O (O) A CK-MB fraclion delermination would have been a much more sensilive way lo detecl acule MI lhan lotal CK level.

26. A friction rub is audible in a 68-year-old male with Ihe gross appearance of ¡he heart shown here. Which of Ihe following laboralory test lindings is most likely prcsenl in Ihis patienl?


'114

Por! 2

DISEASES OF ORGAN SYSTEMS

o (A)

Positive anlinuclear antibody al 1:512 O lB) Elevaled anli-slreploIYl!iin O tilu O (C) Urea nitrogen leve! of 98 mgldL O (O) Elevatcd renin le"el O (E) Serum crealine kinase (CK) of 500 VIL

mild pulmonary hypertension. Echocardiography shows all valves lO be normal in configuralion. \Vhich of lhe following iesiOlls did the angiogram rnosl likely show?

O O O O O

(A) Atrial septal defect (ASO) rB) Tetralogy of Fallot (C) Aonlc coarclation (O) Total anomalous pulmonary venous relum CE) Patenl duetus arteriosus (POA)

J l. A 49-year-old previously heallhy female reports having had se\'eral "fainting spells" in lhe last 6 months. In caeh case. she regained consciousncss after only a few minutes. Her blood pressure is normal. She has good carotid pulses with no bruils. Which of lhe following cardiac lesions is most likely lo be prescnl?

O (A) Pericardial effusion O (B) Len alria! myxoma O (e) Bicuspid aortic valve 0(1) Mitral valve slenosis O (E) Len anterior descending arlcry Ihrombosis

27. From tlle gross aJ)pearance of lhe aortic val\"e shown here, which of the following causes most likely contribulcd lO lhe lesiOll?

O (A) Chromosomal aneuploidy

O rB) Aging O (C) Syphilis O (O) Atllerosclerosis O (E) Systemic lupus erythcmatosus 28. A 32-year-okl Nonh American Caucasian female presenls wilh iocreasingly severe symploOls of congeslive heart failure (l\'U 2 weeks. She has no previous hislory uf hearl disease. An e1cclrocardiogrnm shows soOle runs of ventricular lach)'cardia. and an endomyocardial biopsy shows focal myocyle necrosis a!ong wilh a Iymphocytic infiltrate. She is most likely lO have an infection wilh which of the following 0I1;anisms'! O (A) 1: CI'II:(.i O (B) S. viridll1lS O (C) Coxsackievirus A

O (O) TOXOIJlosma O (E) S. ollrells

(A) (8) (C) (O) O (E)

O (A) Diabeles mellitus O (B) Marfan syndrome O (C, Bicuspid aonic \'alve O (D) SYSlemic hypcnension

O (E) lnfeclive endocarditis

--

-

Libman-Sacks endocardilis Cianl cell myocarditis Rheumalic heart disease Alrial myxoma Fibrinous pericarditis

JO. A hanih. waxing and waning, machiner)'-like Illunnur is auscultated in lhe upper chesl of a 2-year-old child wilh a history of infeclive endocarditis. Angiography reveah

_

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.

....

.

'-

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gOlldii

29. While touring a 171h cenlury European mansion, yoo nol.ice thaI lhe bed in the bedroom wa.. designed so mat lhe OCCUpanl slept while sitting up. Whal cardiac disease in the 4O-)'ear-okl wife uf the mansioo's owner al lhal lime woold best explain lhis bed design?

O O O O

32. A 60-year-old male presenls with worsening cough and orthopnea. Echocardiography revcals marked len venIricular hypenrophy and severe aonic slenosis. The remaining cardiac val ves are normal. A coronary angiogram demonslrales no significanl coronar)' arterial narrowing. Which of lhe following condilions best account.l> fOr these findings1

... ...

....... ~ ••

-~

......-- - =- ... .,

~

-~

... -.....

.-.;;..,..~

....,

.'

33. 11le microscopic appearance uf the myucardium uf a 45-year-old male is seen here wilh a Prussian blue Slain. Hc hOO complained of increasing fatigue. exenional dyspnca, and chest pain. Which of lhe foilowing functional cardiac dislurhances was mosl likcly presenl?

O (A) Dynamic Oh"lruction to lefl venlricular outnow O (B) Reduced venlricular compliance resulting in ¡Illpaired venlricular ti\1ing in diastolc


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o (C)

THE HEART

115

Milral and lricuspid valvular insufficiency

O (O) Lack of \'entncular expansion during diaslole O (E) Re<!uced ejection fraclion from decreased contraction

34. Physical examination reveals jugular venous distenlion in the neck of a So-year--<lld male. even when he is sitting up. He also has an enlarged aOO lender liver Ihat can be feh 10 cm below lhe righl coslal margino Pitling edema is observe<! on his lower extremilies. A cheSI radiograph reveals large pleural effusions. lñoracentesis on lhe righl yields 500 mL of clear fluid with few cells. The most Iikely cause of Ihis c1inical piclure is

O (A) Tricuspid valve slenosis O (B) Acute myocardial infarclion O (C) Pulmonary valve stenosis O (O) Chronic obslructive lung disease

O (E) Primary pulmonary hypertension 3S. Three weeks arter a bout of acule pharyngitis. a 10year-old female develops subculalleous nodules over Ihe skin oC her arms and torso. She also manifesls choreiform movements aOO begins to complain of pain in her knees and hips. particularly with movemem. Auscultation of the Chesl Te\'eals an audible friction rub. Which of the foBowing serum laboratory test fiodings is mos! characleristic of lhe disease affecting Ihis patiem?

37. This rigure, demonstraling lhe gross appearance of Ihis hearl al autopsy in a 25-year-old male. is rnost consistenl with which of lhe following underlying causes of dealh?

O (A) Elevate<! level of cardiac lroponin I O (B) Posilive antinuclear antibody lest

O (A) Diabeles mellitus

O (C) Elevated crealinine level

O (B) Disseminated. tuberculosis O (C) Scleroderma

O (O) Positive rapid plasma reagin tesl O (E) Elevated anti-slTepr.olysin O level

O (O) 81unt chest trauma O (E) Malignanl melanoma

38. A 40-year-old female diagnosed with adenocarcinoma of lhe slomach with metaslases lO liver suffers a right cerebral infarclion. A few weeks later. she develops severe dyspnea, and a pulmonary ventilalion-perfusion SC3fl shows a high probability for pulmonal)' lhromboembolism. Which of the following cardiac lesiolls is most likely lo be presenl? O O O O O

(A) (B) (C) (O) (E)

Cardiac metastases l..eft ventricular muml lhrombosis Constriclive pericarditis Nonbaclerial Ihrombotic endocarditis Calcific aortic valvular slenosis

36. 11le microscopic appearance of Ihe proximal \eh anle· rior descending arlery shown in Ihe figure is seen at autopsy of a 37·year-old female. Which of the following condilions is probably !he uOOerlying cause of dealh?

39. A lnonlh after ortbotopic cardiac transplantation for ischemic cardiomyopalhy in a 55-year-old male, an eodomyocardial biopsy performed. 11le biopsy shoW5 minimal focal myocyle necrosis wilh scattered Iymphocytes and plasma cells. Which of the following pathologic processes besl accounls for lhe biopsy rindings?

O O O O O

O (A) 0(8) O (C) O (O) O (E)

(A) (8) (C) (D) (E)

Marfan syndrome Acule leukemia Polyarteritis nodosa Diabetes mellilus Chronic alcoholism

Autoimmunity Ischemia Infection Rejection Apoptosis


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116

Part 2

DlSEASES OF ORGAN SYSTEMS

lying condition thal is mosl likely to be presenl in lhis palient ls

O (A) O (B) O (C) O (O)

Rheumalic hean disease Hemochromatosis Chagas disease O;abeles mellitus O (E) ldiopathic dilate<! cardionlyopathy 44. A 19-year-old male suddenly collapses. He is brouglu lo Ihe emergency room. where he is found to be hypolensive. He js found lO have an elevaled total CK level w;lh CK-MO fraclion oC 10%. Which of lhe following underlying conditions ¡s he mosl like1y lo have?

40. A 40-year-old female experiences increasing dyspnea. and lhe gmss appearancc of her heart is shown here. These ctlanb'e5 in lhe hean most likely resulled after an infeclion wilh O (A) 7i'epollema pal1idum

O (B)

Stal)/¡ylococclt.~all"ejL.~

O (e) Coxsackieviru.~ O O (O) Group A StreptococclIS O (E) Toxopla.5tll(1 gOl/dii

41. A 15-year-old male complains of pain in his legs when he mus more Ihan 300 m. Physical examination reveals a blood pressure of 165190 mm Hg along with a temperature of 36SC. pulse of 76. and respiration rnte of 22 per minule. Ilis radial pulses are 4+. and the dorsa1is pedis pulses are I +. Arterial blood gas measurement reveals nonnaI oxygen saturalion. Which of lhe following lesions is probably presem?

O (A) Tricuspid atresia 0(8) O (e) O (O) O (E)

Coaretation of lhe aona Aortic valve Slenosis Patenl duCluS arleriosus Transposition of Ihe great arteries

42. Physical examination of an asymplOmatic 2-year-old child reveals a low-pitched cardiac murmuro An echocardi· ogram shows presence of the ostium secundulTI. wilh a l· cm diameter defecto Which of the following dinical abnormalilies is masl Iikely to be found in this child?

O (A) Pulmonary hypertension O (B) Pericardial effusion O (e) Left-Io-right shunl O (D) Mural thrombosis O (E) Cyanosis 43. A 44-year-old previously heallhy male has experienced worsening exereise lolemnce accompanied by marked shortness of breatll for lhe past 6 months. A chesl radiograph shows an enlarged heart and pul mona!)' edema. An echocardiogram shows four-chamber cardiac dilation and demonstrates mitral and tricuspid valvular regurgitalion. A coronary angiogram demonslrates no more than 10% nanowing of lhe majar coronary anenes. The under-

O (A) Heredilary hemochromatosis O (O) Manan syndrome O (e) Down syndrome O (O) OiGeorge syndrome O (E) Familial hypercholesterolemia

45. Myocardilis in a 140-year-old female is chanlcteri7..ed microscopicaBy by focal interstilial infiammation wilh Aschoff nodules and Anitschkow cells. This is accompanied by lhe gross appearance of a verrucous endocardili!> and a fibrinous pericardilis. This pancardilis resol ves over Ihe en!>uing weeks. Which of Ihe following complications oC Ihis process is mosl likely lo be seen in Ihis patient 20 years 'ater? O (A) Aortic slenosis O (B) Righl ventricular dilation O (e) Conslrictive pericarditis O (D) Mitral ,'ah'e prolapse O (E) Left ,'entricular aneurysm 46. 1lle ~sence of hemorrhage and conlraction bands in necrolic myocardial fibers ¡s most likely to be seen in which of lhe following?

O (A) Subendocardial infarel resulling fmm diffuse narrowing of coronary arteries

O (E) Transmural ¡nfarct caused by complele Ihrombolic ocdusion oC a coronary arte!)'

O (e) Transmural illfarcl complicaled by mural Ihrombosis O (O) TransllIural iufaret that is reperfused by Ihrombolylic Iherapy O (E) A healing transmural myocardial infarel


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COOpter 12

47. 111e light microscopic appeamnce of the leh ventricular free wall shown on the previous page fram a 48-yearold female is mosl consistent with

O (A) Viral myocardilis O (B) Two-day-old myocardial infarction (MI)

O (C) Acule rheumalic myocarditis O (O) Septic embolization O (E) Restrictive cardiomyopathy

THE HEART

â&#x20AC;˘

117

2. (B) Bioproslheses are subject ro wear and tear. 1l1e leaf1e(); may calcify, resulting in stenosis, or lhey may perforate or tear, leading lo insufficiency. Paravalvular leaks are rare complications of the early posloperative periodo Hemolysis is nOI seen with bioprostheses and is rare with modern mechanical prostheses. Thrombosis with embolization is an uncommon complication of mechanical proslheses, lessened by anticoagulant lherapy. Myocardial infarction fram embolizalion or from a poorly positioned valve is rareo BP6 32B PBD6 57B 3. (8) ll1e severity of the obstruction to the right ventricular outnow determines the direction of now. Ir the pulmonie stenosis is mild. then the abnormality resembles a VSD, and the shunt may be leh to righl with no cyanosis. With significanl puhnonary outnow obstruetiotl, the right ventricular pressure may reach or exceed systemic vascular resistance. alld lhe blood gelS shunted from right to left, producing cyanotic healt disease. Even if pulmonic stenosis is mild al birth. Lhe pulmonary orifice doe~ not expand prolX)I1ionalely as the heart grows. and hence cyanoljc heart disease supervenes. BP6 335 PBD6 595 4. (e) 111is patient developed acute lefl vemricular failure. an uncommon complication of acute rheumatic fever. Ouring the acule phase palients develop pancarditis. and hence pericarditis. valvulitis. myocarditis. and ventricular dilatation are all likely. Fibrosis and fusion of the mitral valve leaflets lake several weeks lo months to develop. BP6322-324 PBD6570-572

48. A 2-monlh-old infant has been cyanotic since binh. The baby has worsening congestive heaJ1 t"ailure. Based on lhe gross appearance of the heart shown here. this inrant's congenital heart disease is best e1assified as

O O O O

(A) Tetralogy of Fallot (B) Puhnonic stenosis (C) Truncus arteriosus (O) Transposition of the great vessels O (E) Aortic stenosis

ANSWERS l. (E) His symptoms are typical for angina pecloris when coronary arlery narrowing exceeds 75%. Persons wilh rheumatic heart disease are affected by slowly worsening congeslive heart failure (CHF). Pericarditis can produce chesl pain. allhough nol in relation lO exercise. and il is nol relieved by nilroglycerin. Cardiomyopathies resuh in hearl failure but wilhout chest pain. Ca1cific aortic stenosis leads to lefl-sided CHF, and the extra workload of the leh ventriele may cause angina pectons. However, calcilic aortic stenosis (in Ihe absence of a congenital bicuspid aortic valve) is rarely symplomatic at 50 years of age. BP6312 PBD6554

5. (O) This is a large VSO. By the age of 5 years, such an uncorrected defect causes marked shunting of blood from lefl lO right, causing pulmonary hypertension. However. lhe extent of cardiac malfunction is not great enough lO produce renal disease, mainly because there is no syslemic hypertension. Congenital heart disease is not an antecedent lO ischemic heal1 disease in most ca<;es. The OiGeorge syndrome, with T-cell immune deliciency from Ihymic hypoplasia. can be accompanied by cardiac defeclS. but Ihis condition is uncommon and accounts for a vel)' small fraclion of aH congenilal cardiac defects. Dilated cardiomyopalhy is an idiopalhic eondilion in IllOsl cases. It is characterized by a large, flabby hearl with dilation of all four chambers. BP6 334 PBD6 594 6. (C) This enlarged and dilaled heal1 has a large ventricular aneurysm. The aneurysm most likely resulted from a weakening of lhe ventricular wal! al lhe site of a healed, old MI. Because of lhe damage lO lhe endocardial lining and Slll"is and turhulence of blood Ilow in lhe region of the aneurysm. mural thrombi are likely lO develop. When detached. Ihese thrombi embolize to systemic circulation and can cause infarcts e1sewhere. Cardiac IUpture and acule pericdrdilis occur S lO 7 days after an acute MI. Cardio-genic shock also OCCUTS very early after an acute MI. Con~ strictive pericarditis follows a previous suppurative or luberculous pericarditis. BP6316 PBD6563


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118

Par! 2

r >

DIS€ASES OF ORGAN SYSTEMS

7. (E) This aonic valve ha... large, destruclive vegetatiollS typical for infecfive endocMrditis caused by highly v¡rulen¡ orgallisms such as S. al/reus. lñe verrucOllS vegetalions of aCUle rheumalic fever are small aud nondeslrucfive, and lhe diagnosis i!> suggesled by an devaled anti-streptolysin O ,iler. A positive antineolrophil cYloplasmic antibody delerlIlinalion suggests a vasculitis., which is no! likely lo involve cardiac val ves. An elevared CK-MB level suggests myocardial, nol endocardial. injury. A posilive doublestranded DNA fiOOing suggests a diagnosis of syslemic lupus erythcmalosus. which can prodoce a IlOndeslrUclive Libman+Sacks endocarditis.

BP6 326-328 PBD6 573-575 8. (A) Thc cJinical and morphologic fealUres are 1}'PicaI of hypertrophic cardiomyopalhy. This disease is familial in 50% of cases alld is usually lransmiued as an autosomal dominallt lrail. lñe gcne¡jc defect5 affect the proteins thal encocle proteins of thc cardiac contracúJe eJemenl". The mosl common mutalion in lhe inherited fonns affects the J3-myosin hca\'y chain. Chronic a1coholism can give rise lO dilated cardiolllyopalhy, and amyloidosis causes reslriClive cardiolllyopathy.

BP6 331-332 PBD6 581-583 9. (A) Thc most common causes for hemorrhagic pericardilis are mcla.<aalic can::inoma and luberculosis. GrOllp A Streptocoeeu.f is responsible for meumalic fever. which acutely can lead lO a librinOlls pericarditis and to serous etTusions fmm congeslivc fa¡lure in the chronic fonn_ Coxsackieviruses are known 10 cause myocarditis. ClUldida is a rare card¡ac infeclion in immullOCompromised persons. S. al/rellS is besl known a" a cause uf infeclive endocarditis.

BP6 337 PBD6 588-589 10. (E) 1'his palienl is al a high risk for developing complicalíans of infeclive endocarditis. These lindings suggesl thal she developed slaphylococcal septicemia followed by endocarditis of Ihe mitral val ve. The impaired fUllctioning of the mitral valve (masl likely regurgitation) would give r¡se tO lefl atrial dilalioll. Tlle cxlension of inlection from Ihe valve surface lO Ihc underlying myocardium produces a l"illg ahscess. Focal or diffuse glomcrulonephritis is a complication Ihm dcvclops because antigen-anlibody complexes. produced in response lO persisting infection, deposit on the glomerular basemenl membrane. Emboli from lhe milral \'ah'e would go illto syslemic circulation and give (ise lO brain abscesses. Myxomatous de~eneration of lhe mitral va¡ve resulL~ from a defecl in connective tissues. whether wen dcfincd or unknown. 1ñc mitral valve leaflels are enlarged, hooded, aud redundam.

BP6326-328 PBD6569, 574-576 11. (A) Prolonged fever. heart murmuro mild spJenomegaly. aOO splilllcr hemorrhages suggest a diagnosis of infective endocardilis. 1ñe valvular \'egetalioos wilh infectivc enOOcardilis are quite friable and can casi]y break olT and embolize. l1Je lime course of weeks suggests infection fmm a less \'irulem organismo such a.. S. l"i11OOIlS. T. CIllV aOO coxsackievirus B are eauses of myocardilis. Candida is no! a common cause of infcclivc cndocarditis bul may be

seen in immullocompromised patients. Tuberculosis ¡uvol,,· illg 111e IlCMrt mosl oflen manifesLS as a pericarditis.

BP6326-328

PBD6573-575

12. (A) In lhe period irnmediately after coronary thrombosis. arrhYlhmias are Ihe most imponant complication and can lead lO suelden cardiac death. It is believed lhat, even beto«: iscilemic injury manifests in lbe heart, there is greatly increased eleclrical irritability. Pericarditis and rupture are seen severa! days later. An aneurysm is a lale complication from healing of a large transmural infarction; a muml lhrombus may fill an aneurysm and become a sooI'Ce for embolL Ir portions of tlle coronary thrombus break off aod emboli7..e. they go into smaJler arterial branches in !he dislribulion already affecled by ischemia.

BP6314-316 PBD6 562 13. (E) His symptoms suggesl aortic dissection. Fragmemation of elaslic fibers in lbe media of the aorta greatly weakens the walJ of lbe aona alld predisposes to aortic dissecliOlL Such cyslic medial necrosis can occur in patients with long-standing hypenension or in those with Marfan syndll)me.

BP6 301-302, 325-326 P8D6 527-52B, 569-570 14. (1) She has myxomatous degeneration of lbe mitral valve (i.e.• "f1oppy milral valve"), a cOlldition seen in aboul 3% of the popol:uion. There is a potenlial risk fOl" rupture with acUle insufficiency. requiring mitra! valve replacemenl. Other potential complicatiolls indude infective endocarditis or IlOlloocterial thromOOtie endocarditis wilh emboli7..a¡jon and arrhythmias.

BP6325-326 PBD6569-570 15. (K) Nonbaclerial Ihrombolic endocarditis oflen aceompanies lerminal cancer. This may be a fealure of Trousseau syndrome, a paraneoplastic syndrome with a hypercoagulable slale. Although Ihe vegelalions are bland and nondestruclive. they are friable and can easi]y break off and embolize.

BP6326 PBD6567-577 16. (.1) He probably has 3n infeclive endocarditis. and Ihere is evidence of syslemic septic emboli7..alion to produce lhe cerebral abscess. Such syslemic embolization suggests lhm the lesions are 011 lhe lefl side of the heart. Although righl-sided lesions suongly suggest injecfion drug use as a cause for infective endocarditis. injection drug users are only slightly more Iikely lO have right-sicled lesions. 'rhey can have right- and lefl-sided vegetations.

BP6326-32B PBD6574-576 17. (U) Hypenension is an importam cause of lefl ventricular hypertrophy and failure. Left-sided heart failure leads lO pulmonal}' edema wilh dyspnea. Obstructive (e.g.. emphysema) and reslriClive (e.g.. silicosis) lung diseases lead lO pulmonal}' hypertension with rigtlt heart failure from cor pulmonale. Iikewise. righl-sided valvular lesions (Le., lricuspid or pulrnonic vah'es) predispose to righl heart failure. Alcoholisrn can lead lo a dilated cardiomyopalhy Ihal affecls lefl and right heart funclion.

BP6 309 PBD6 549


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Chopler 12

THE HEART

119

18. (e) This paliem has evidence of pulrnonary hyper1ension (pulrllOllaf)' atherosc1erosis) and righl-sided heart faiture. When tms is secondary to lung disease, il is called COl" pulmonale. caused most oflen by pulmonary emphysema aOO olher obslructive lung diseases. Restriclive lung diseases can also lead lo cor pulmonale. A VSD predominantly has lefl ventricular hypertrophy. although afler years lhe lefl-to-right shunl can cause pulmonary vascular resislance lo rise and reven;e the shum; at this stage righl venlricular hypertrophy develops. A large pulmonary embolism can produce acule cor pulmonale, mainly with righl atrial dilaliort RHD affecls mainly milra! aOO aortic valves. A hypertrophic cardiomyopathy affects left ventricular funcüon the mosL

23. (e) The kinelics of CK, CK-MB. and troponin I ele· vations afta MI are important. Total CK activilY begins to rise 2 to 4 hours after an MJ. peaks at aboul 24 hours, and retums to normal by 72 hours. Troponin I levels begin 10 rise al about the same time as CK and CK·MB but remain elevated for 7 to 10 <lays. Tocal CK oclivilY is a sensilive marker for myocardial injury in Ihe lirsl 24 lo 48 hours. CK-MB offers more specificily but nol more sensitivity. Myocardial rupllLre occurs 5 lo 7 days after myocardial necrosis. This palienl developed an MI on the day of t.he shoulder pain. W!len he wenl lO lhe doctor on day 3, the CK levels bad ret\lmed 10 normal, bol ITOponin I le\'els were still elevaled. Three days later, he suffered O1plure of lhe infarel.

BP632O-321

BP6317 PBD6561

PBD6565-566

19. (e) She has lindings of floppy mitral valve, a condilion Ilmt is most often asymplomatic. When symplomatic, il can cause fatigue, chesl pain. and arrhythmias. Pulmonic stenosis is most orten a congenilal heart disease. Valvular vegetatiolls suggesl an endocarditis, and a murmur is Iilety to be heard with infeecive endocarditis causing valvular insufficiency. A PDA causes a shrill s)'slolic munnur. Tricusptd regurgilation is accompanied by a O1mbling s)'slolic munnur.

BP6325-326 PBD6 568-570 20. (A) Hypenrophic cardiomyop.'l.thy is the mosl common cause of suelden unexplained death in )'O\lI1g athletes. In trus condition, there is asymmelric seplal hypertrophy Ihal reduces Ihe ejeclion fmction of lhe left ventricle, parlicularly during exereise. HislOlogically. hapha7..ardly arranged hypertrophic m)'ocardial fibers are seen. Hemochromatosis gives rise lo a reslrictive cardiomyopathy in mieldle age. Tach)'zoites of T. gondii signify myocardilis, a process that may occur in immunocompromised persons. RHD with chronic valvular changes would be unusual al this age, and the coun;e is mosl oflen slowly progressive. Valve destrucLion with vegetations is sccn in infcctive endocarditis. This should be accompunied by signs of sepsis.

BP6331-332 PBD65B1-5B3 21. (8) The markedly Ihickened left ventricular wall is characlerislic for hypertrophy from increased pressure load frorn hypertension, whi<:h is oflen aS$ociated with chronic renal disease. Otronic aIcohoLisrn is associated with a dilated cardiom)'opalhy. Pneumoconioses produce restrictive lung disease wilh cor pulmonale and predominantly righl ventricular hypertrophy. Hemochromalosis leads to a restriclive cardiom)'opathy. Diabeles mellitus accelerales atherosclerosis, leading to ischemic heart disease and MI.

BP6319-320 PBD6564-565 22. (A) The c)'anosis al Ihis early age suggests u righl.to1efl shunt. and lelralog)' of FallO( is the lTlost common cause for cyanolic congenilal heart disease. 1be cerebral lesion suggests an abscess as a consequence of Seplic emooli7..alion from infecli\'e endocarditis, which can complicate congenital heart disease. ASDs and PDAs 1cad to leftIo-right sbunts. Coarctation is 1101 accompanied by a shunl aOO cyanosis. A bicuspid valve is asymptomari<: until aduh life in mast cases, and there is no ShUlll.

BP6 335-336 PBD6 595

24. (C) He has symptoms of an acule MI, and of lhe enzymes lisled. CK-MB is lhe most specilic for myocardial injury. The levels of Ims enz,yme begin lo rise withjn 2 to 4 hours of ischemic myocardial injury. Lipase is a marker for pancrealitis. AST is fouOO in a vanelY of tissues. and therefore elevated levels are nOl specific for m)'ocardial ¡njul)'. ALT eievalion is more specific for liver injury. The elevation of lDH-I compared wilh lDH-2 suggests m)'~ cardial injury. OOt LDH aclivilY peaks al 3 da)'s after an MI.

BP6 317 PBD6 561 25. (e) This palient has 75% slenosis of Ihe left anterior descending bmnch of Ihe coronary artery. This degree 01' slenosis prevents adequate perfusion of lhe heart when myocardial demand is increased, as occurs durillg exertion. Hence, the patient had angina on exertion. In recent weeks, lhe patient has developed ullSlable angina which is mani· fesled by increased frequency and severity of lhe auacks aOO angina al resto In mest palienls. unslable angina is induced by dis01plion of an a1herosclerolic plaque followed by a mural Ihrombos and, possibly, dh;tal emboli7.ation, vasospasm, or bolh. Hypertrophy of the !lean is unlikely in Ibis case because 111ere is Ileilher hypertellsioll nor a valvular lesiono AII other possibililies can theorelically give rise lO a similar picture. but plaque disruplion with mural Ihrombosis is the most common anatomic linding when the patient develop; unslable angina. It is important lO recog· ni7.e trus, because unstable angina is a harbinger of MI.

BP6312 PBD6554-555 26. (C) This is a fibrinous pericarditis. The most common cause is uremia from renal failure. Posilive antinuclear anlilxxly suggests a collagen vascular disease, such as systemic lupus erylhematosus. Such diseases lend to be ac· companied by a serous pericardilis. An elevalion of serum CK occurs in MI. An acule MI may be accompanied by a librinous exud<\te o\'er lhe area of ilúarclion, nO( lhe diffuse pericarditis seen here. Elevation of the amistreptolysin liler accompanies rheum..'l.lic fever. AcUle rheumatic fever may Jmduce a fibrinous pericarditis. bot rheumatic fever is nO! common al this age.

BP6 337 PBD6 588 27. (B) This is ca1cific aortic Slenosis, a degenerative change that muy occur in a normal aortic valve with aging.


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Port 2

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DlSEAS.ES Of ORGAN SYSTE/V1S

COllgenital anomalies wilh chromosomal aneuploidies (e.g., trisomy 21) are not likely lo be associaled with aortic slenosis or a bicuspid val ve. Wilh syphilis. lhe aortic root dilares and results in aonic insuffJeiency. Atherosclerosis does Il<ll produce valvular disease from involvement of the \'alve itself. S)'stemic lupus erythematosus can sometimes give rise lO small sterile vegetalions ()11 milr.l.! or lricuspid valves, but these rarely cause \'alve disease.

BP6 324-325 PBDó 567-568 28. (O Focal myocardial necrosis wilh Iymphocyte infilIrale is consislent with viml myocarditis. This is T10l common, and many cases may be asymplomatic. In North America, ~t cases are caused by coxsackieviruses A and B. This illlless mal' be self-Iimiled. end in suelden dealh, or progress 10 chronic hean failure. T. cruzi is the causalive agelll for Chagas disease, seen mosl Orten in childrell. Worldwide, this is probably the I110SI commOll infectious cause 01' myocardilis. Septicemia with bacterial infecliolls mal' involve the heart. but the palient probably is ver)' ill wilh mul1iple organ failure. T. gOluJii mal' cause a myocarditis in immullocompromised patienls.

BP6329-330 PBD6584-585 29. (e) Paroxysmal nocturnal dyspnea is a feature of leh-sided congestive heart failure. aod RHD JTlOSI often illvoh'es lhe mitra!. aortic. or both valves. RHD was more common before availability of anlibiotic therapy f()r" group A I3-hemol)1ic slreptococcal infectioos. Giant cell myocarditis is a rare cause for cardiac failure tbal can be rigil! and left sided Libman-Sacks endocardilis, seen wilh systemic lupus erythematosus. does not Iypically impair ventricular funaion significantly. An alrial myxoma is most often on the left, but the obstructioo is oflen inlermiuent. Fibrinous pericarditis can produce chesl pain, bUI the amoont of accompanying nuid is often nol greal, and hence cardiac fUllction is not impaired.

BP6 310 PBD6 549

been symptomatic for years. Coronary anery thrombosis results in an acule ischemic e\'em.

BP6338 PBD6589-590 32. (O 1bere is a tendency for bicuspid valves to calcify with aging. which can eventually result in stenosis. In individuals with congenilalJy bicuspid vah'ts. symplOffiS appear by 50 10 60 years of age. By COlllrasl. ca1cific aortic stenosis of tricuspid valves manjfests in lhe 5evenlies ()r" eighlies. Ischemic heart disease, expecled with diabetes mellilus. does nOl lead lO valvular stenosis. In Marfan syndrome, the aortic r()()( dilates lO produce aonic valvular insuffidency. Hypenensioll accounls for len ventricular hypertrophy, bUl the aortic valve is not affecle<!. With infective endocarditis. he should be septic. and the valve lends tO be deslroyed, leading to insuffidency.

BP6 325 PBD6 568 (8) The exlensive iron deposilion signifies helllochromatosis, which reduces ventricular compliance Illarkedly, resulting in a restriclive cardiomyopalhy. Dynamic len ven· tricular oulOow obstruaion is characteristic for hypertropic cardiomyopalhy. Valvular insufliciency of mitra! and lricuspid vah'es can occur with a dilaled cardiomyopathy, wtüch also reduces colltractililY and ejection fmetion. I..ack of diaslolic expansion suggests a colIslriaive pericanlilis. 33.

BP6332 PBD6586-587 34. (O) His findings poim to a pure righl-sided conges· live hean faiJure. This can be caused by righl-sided valvular lesions such as lricuspid or pulmonic :o;tenosis. bul lhese are rareo Moch more common is pulmonaf)' h)'penellsion resulling from obstructive lung diseases such as elllphy· serna. Prilllary pulnM>l1ar)' h)'penension can also cause righl-sided heart failure. bul it is a much less common cause Ihan are lung diseases. Because acule MI usuaUy affecls the left venlride, left·sided heart faiJure is more commoCl in Ihese patients. Chronic left heart failure can eventually leOO lO righl-sided hean failure.

BP6309-31O PBD6549-55O 30.

(E) Although oflen nol lurge in size, a POA can

produce a significan! murlllur and predispose lo endocarditis. The left-Io-righl shunt eventually results in pulmonar)' hypel1ension. An ASO is ulllikely lO produce a loud murmur because of lhe minimal pressure difTerenliaJ belweell the arria. Oecause tetmlogy oC FallO! has pulmonic stenosis as a componellt, no pulmonary hypenellsioll results. AOftic coarclalions by themselves produce no shullting aod no pulmonary hypel1ension. Total anomalous pulmonary Vtnous mum is Il<ll accompanied by a murmur because of lhe low veoous pressure.

BP6 335 PBDó 594 31. (B) An atria! rnyxoma can have a baIl-valve effecl tbal inlenniltelltly ocdudes the mitral v¡¡lve. leading lO the syncopal episodes. MosI pericardial efTusKms are not large and do nOl cause major problems. Large effusioos could leOO 10 tamponade, but this is not an inlermittent problem. CaJcificalion oC a bicuspid valve can Ie.'ld to stenosis with heart failure. but this condition is progressi\'e. By lhe time len atrial enlargemenl with muml Ihrombosis and risk of emboli7.<1lion occurs from milral slellosis, she should have

35.

(E) The findings suggesl acule rheulllatic fever, which can involve any or all layers of the heart. Because rheumatic fever follows slreplococcal infecliOlls, the amislreplolysin O liter is elevaled. Ülrdiac troponins I aOO T are markers for ischemic m)'ocardial illjury. Ahhough their levels may be somewhat elevaled because of acute m)'ocardios Ihat occurs in meum3lic fever, lhis change is 1101 a characteristic of RHD. l..evels of antinudear antibodies could be elevated with systemic lupus erythemalosus, which is fIlost likely to produce a serous pericarditis. 1lJe slrains of Group A St,.cptOC:OCCU.f lhat leOO to acute rheu· matic fe\'er are nOl likel)' 10 cause glomerulonepbrilis. and an elevate<! creatinine level is therefore not likel)'. Positive rapid plasma reagin lesl suggests s)'philis. but the dinical features are noc. those of syphilis.

BP6322-324 PBD6570-572 36. (D) This coronary artery shows marked narrowing from alheromalous plaque, complicated by a recelll Ihrombus. Atherosderosis is accelemled wilh diabetes mellilus. When a premenop"'-lUsai femule develops severe atheroscle-


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COOpter 12

rosis. as in Ihis case. underlying diabeles meUilus must be strongly suspected. The cystic medial necrosis with Marfan syndrome most often involves the ascending aorta and predisposes to dissecuon Ihal could involve coronaries, alIhough with external compression. Polyarteritis nodosa can involve coronary arleries and give rise lo coronary Ihrombosis. However. in Ihese cases, Ihe vessel wall is necrolic and inAamed. Palients with leukemias can develop hypercoagulable slales. When Ihis occuo;, Ihere is widespread Ihrombosis in nonnal blood vessels. Chronic a1coholics oflen have less atherosclerosis than do persons of Ihe same age who do nol consume large amounls of a1cohol.

8P6311

P8D6551-552

37. (D) This is a massive hemopericardium wilh pericardial lamponade. The blunt tmuma ruplures the myocardium. Ischemic heart disease wilh diabeles could lead lO a ruptured MI. bul thal would be unusual at this age. Tuberculosis can cause a hemorrhagic pericarditis. typically withOUI lamponade. Scleroderma is mosl likely lo produce a serous effusion. Mela.l1oma and other metastases can pro-duce a hemolThagic pericarditis withoul lamponade.

8P6 337 -338 P8D6 587 38. (D) These sQ-caUed mamntic vegetations may occur on any cardiac valve bul lend lO be smaU and do not damage the valves. However. they have a nasly lendency to embolize. They can occur wilh hypercoagulable slales Ihal aecompany certain malignancies. especially mucinsecTeling adenocarcinomas. This panmeoplaslic slme is Icnown as Trousseau syndrome. Cardiac melastases are uncommon, and lhey tend to go lo Ihe epicardium. Mural Ihromboses occur when cardiac blood now is altered, as in a ventricular aneurysm or dilaled atrium. Metastalic lumor can encase Ihe hearl lO produce constriction, bul Ihis is rareo Ca1cific aortic stenosis occurs al a much older age. usuaUy in Ihe eighth or ninlh decade.

8P6 326 P8D6576 39. (D) Endomyocardial biopsies are roulinely perfonned after cardiac transplantalion lO monilor rejection. This is nol an autoirnmune process, bccause lhe lransplant is "foreign" tissue lo lhe hos!. MOlllhs {O years latero Ihe coronary arteriopalhy characlerislic for cardiac lransplants may produce ischemic changes. húection is a definile pos!<ibiIiIY. because of the immunosuppressive drugs administered {O keep the rejeclion process under control. although plasma cel1s are not a key feature of acule infeclion. Apoplosis is nol lypically accompanied by inAammation to this degree.

8P6 329 P8D6579 40. (D) This mitral valve shows shortening and thickening of the chordae typical for chronic rheumatic valvulitis, aOO Ihe small verrucous vegetations are characteristic of acule rheumatic fever. RHD develops after a streptococcal ilúcction; Ihe inunune response against Ihe b..'icleria damages the heart because streptococcal antigens cross reaet with Ihe heart. Syphilis leads lO aortic root dilation. S. aureus mosl often results in infeelive endocarditis in Ihe hearl. Coxsackievirus B infel,;tion can cause viral myocardilis. Toxoplasmosis is a cause for myocarditis in immunocompromised patients.

8P6321-323 P8D6570-572

THE HEART

121

41. (8) [n aduhs, Ihe coarcL.'ilion is Iypically postduclal. and collaleral branches from Ihe proximal aorta supply the lower eXlremilies, leading lO Ihe pulse differential from upper to lower exlremilies. Diminished renal blood flow increa<;es renin produelion and promoles hypel1ension. Tricuspid atresia affects the righl hearl. Aortic valve slenosis causes left hearl failure and no pressure differential in Ihe exlremities. A PDA produces a lefHo--righl shllnl. Transposition results in a righl-lo-Ieft shunt with cyunosis.

8P6336 P8D6596-597 42. (e) Osleum secundum is the mosl common form of ASD. Because atrial pressures are low, Ihe amounl of shunting from lefl atrium to righl alrium is nol greal, and Ihis lesion can remain asymplomatic for many years. Evenlual1y. pulmonary hypertension I,;an occur, with reversal of Ihe shulll. Pericardial effusions may occur mllch later, if congeslive heart failure develops. A dilated heart wilh enlarged atria predisposes to mural Ihrombosis. Cyanosis is a feature of a righl-to-Ieft shunt.

8P6333-334 P8D6593-594 43. (E) Congestive heart failure wilh four-chamber dilation is suggestive of dilated cardiomyopathy. Many cases of dilaled cardiomyopalhy have no known cause. Dilation is more prominem Ihan hypertrophy, allhough both are present, and all chambers are involved. RHD should most oflen produce some degree of valvular slenosis. often with sorne regurgitation. and the course is usually lIlore pro-longed. Hemochromalosis produces a reslriclive cardiomy. opathy. Chagas disease affects Ihe righl ventricle more than Ihe left. With diabeles mel1itus and accelerated alherosclerosis, Ihe coronary narrowing should be worse.

8P6330-331

P8D6579-581

44. (E) The laboralory findings suggesl an acule MI. Persons wilh familial hypercholesterolemia have acceleraled and advanced alherosderosis. even by the second or third decade. Hereditary hemochromalosis may resull in an inlilImlive cardiomyopathy wilh iron overload. more typically in Ihe fifth decade. Marfan syndrome may resull in aortic dissection or floppy milral valve. DiGeorge syndrome can be associaled with a variely of congenilal heart defcclS. bul survival wilh this syndrome is usually limiled by infcclions from the cell-medialed immune deliciency.

8P6317

P8D6561

45. (A) TItese findings poi ni to acute rheumatic fever. Chronic rheumalic valvulitis with scarring can follow years laler. TIte mitral and aortic valves are most commonly affecled. In almost all cases. Ihe fibrinous pericarditis sccn during the acute phase resolves withoul significant scalTing, and constrictive pericarditis does not develop. Mitral valve prolapse can be seen in palienls with Marfan syndrome, or more commonly, no anlecedem disease can be identified. A len ventricular aneurysm is a complication of ischemic heart disease.

8P6322-324 P8D6570-572 46. (D) Reperfusion of an ischemil,; myocardium by spontaneous or therapeutic Ihrombolysis changes the morphology of Ihe affected area. Reflow of blood inlo vascula-


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122

Part 2

DISEASES OF ORGAN SYSTEMS

ture injured during tlle periad of ischemia leads lO leakage of blood imo lhe rissues (i.e.• hemorrhage). Conlraclion banets are composed of c10sely packed hyperconrracled sarcomeres. They are mosl likcly produced by exaggerated colllractioll of previously injured myofibrils lhal are exposed 10 a higl1 concentJill.ion of calcium ions fram rhe plasma. The damaged cell membrane of Ibe injured myocardial fibers aUows calcium to penelrale !he cells rnpidly.

BP6 316-317 PBD6561 47. (U) 1be picture shows deeply eosinophilic myocar· dial fibers wilh loss of nuclei. a11 indicative of coagulative necrosis. The deeply sraining transven;e bands are caUed contmcrion bands. In belween rhe myocardial fibers are neulrophils. This panem is most Jikely caused by an MI lhal is approximalely 24 10 48 hours old. Wilh viral myocarditis. tbere is minimal focal m)'ocardial necrosis wilh round cell infillmres. Rheumatic m)'ocardiris has minimaJ myocardial necrosis Wilh foci of gl1U1ulornalous inflamma-

lion (i.e.• Aschoff boclies). Seplic emboli resull in focal abscess formarion. ·11..ere is no significanl inflammation with restrictive cardiomyopalhies such as amyloidosis or hemochromalosis.

BP6315 PBD6560 48. (D) 1here is Iransposll1OfI or !he great vessels. lbe aona emerges from lhe right \'entricle. and lhe plI1monic lrunk exilS lhe len ventricle. Unless lbere is anOlher anomalous connection be:tween rigllt aOO lerl circulations. lrus condition is 1101 compatible wirh eXlrauterine life. lhe mosl cornmon conneclions inclu<!e a VSD. PDA. or palen! fora· meo ovale (or ASO). In Ictralogy of Fallot. the aorta overrides a VSD bul is not transposed. In pulmonic and aortic stenosis. Ihe greal arteries are normally posirioned but small. In lruncus aneriosus. the spiral septum that embryologica!l)' separates the great arteries does not develop properly.

BP6 336 PBD6 596


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CHAPTER

13 Red Cells and Bleeding Disorders BP6 COOpter 12 - Too Hemalopoietic ond Lymphoid Sysfems PllD6 COOpter 14 - Red Cel~ ond Bleeding Disorders

1_ For lhe past 6 montllS, a 35-year-Qld female has had excessively heavy mensuua1 flow. She has aloo noticed increasing numbers of pinpoilll hemotThages 011 her lower exlremilies in the past month. Physical examinalion reveals no organomegaly or Iymphadenopalhy. A complete blood COUnl (CBO shows a hemoglobin concenlmlion of 14.2 'El dL. hematocrit of 42.5%. mean corpuscular volume (MCV) of 91 fUred (;ell, platelel count of 19.1.XXYJ.LL, aOO white blood cell (WBC) COUIll of 69501p,L. She has melena on admission to lhe hospital and is given a IransfusiOIl of platelets, bUI her platelet count does nol increase. An emergency spleneclomy is followed by an increase in plalelel coum. The most likely basis of her bleeding lelldency is

3. A 45-year-old female has chronic hepatilis e infection with serum concentralions oC nlanine aminOlransferase (ALl) of 310 VIL. aspartale nminolmnsferase (ASl) of 275 UIL, tOlal bilirubin of 7.6 mg/dL, dirccl bilirubin of 5.8 m'EldL, alkaline phosphatase of 75 VIL, aOO ammonia of 85 IJ.mollL. She has malaise wilh nausea and vomiting. Which of lhe following Inbor'atory test resuhs for hemoslalic funetion is most likely to be abnonnal? O O O O O

(A) lmmunoassay for plasma von WilIebraOO factor (B) Plalelet count (O ProIhrombin time (PT) (D) Fibrin split prodUClS (E) Bleeding time

4. The peripheral blood smear from a 25-year-old female who h..'l.~ a hislaty of arthralgias Cor the pas! 3 years shows hypochromic aOO microcYlie RBes. Despite a slightly decreased hemoglobin and hemntocril, the total RBC COUllt is normal. Tolal serum 隆ron and ferritin levels are wilhin lhe normal mnge. Hemoglobill eleclrophoresis demonstrmes an elevaled hemoglobin A2 leve! of aboul 5.8%. These findings are mosl lypical for

O (A) Abnormalilies in prcx1uclion of platelels by megakaryocytes O (B) Suppression of pluripolent stem cells O (q Deslruclioll of antitxxly-cooled plalelets by lhe spleen O (O) Excessive loss of platelelS in menSlrual blood O (E) Defective platelet-endol:helial interactions

O O O O O

2. A 22-year-old female has h..'1d malaise wilh pharyngitis for a cOllple of weeks. She has Raynaud phenomeJlQl\, and she is diagnosed wilh infectiaos mononucleosis. Her direct aOO indirect Coombs teslS are positive al 4oc. althOllgh llOI al 3T'C. Which of lhe following subslances in her red blood cells (RBCs) can account for lbese findings?

5. A 30-year-old female has splenomegaly and anemia with spherocy!osis. The circulating RBCs demonSlrate an increased oslllOlic fragility on labornlOfy testing. An inherited abnonnalilY in which of lhe following RBe camponenlS besl accounlS for lbese findings?

O O O O O

O O O O O

(A) Immulloglobulin E (lgE) (B) Complement C3b (C) Hislamine (D) hnmunoglobin O (IgO) (E) Fibronectin

(A) Allloimmllne hemol)1ie anemia (8) {3-thalassemia minar (e) lnfection wilh PlasmO(/illln vivax (O) Anemia of chronic disease (E) lron deficiency anemia

(A) Gluc~-6-phosphate deh),drogenase (B) A membrane c)'toskeletal protein (C) a路globin chain (D) Heme (E) {3-globin chain

123.


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DISEASES Of ORGAN S\'STEMS

• . ~

r)

.-

Councsy uf Dr. Robm W. r.kKcllna. Oeparlllll"nl of Pnlholq;y. Uni\·er. ~¡l)' of TeKiI.' Soulh",-CSh:m Mce.liclll SclKJol. o..lIm;. Tx'

6. A 69-year-old previotlsly heahhy female ha<o¡ beeo feel· ing increasingly lire<.l an<.l wcak for severa1 1ll0nths. She is fOllnd lo be anemic. wilh a hemoglobin eoocenlmlion of 9.3 g1<.1L TIlc appearance of hcr periphcral blood smcar is shown herc. Which 01' lhe folJowing conditions should be SUSpecled as lhc most likcly cause fOl' Ihis appearaoce of lhe smear depiaoo herc'!

O (A) Pemicious anemia O (B) GaslroimeslinaJ blood loss O (e) Aplaslic anemia O (O) ,B-lhalas."Cmia majar

O (E) Waml allloimmune hemolylie anemia 7. A 76--year-old fclllaJe 110lices Ihal smal!. pinpoil1l to blolchy area.<o¡ of superficial hemorrhage have appeared on her gums and on lhe skin 01' her arms and legs over several weeks. She is found to llave a normal prOlhrombin time (Pl) and pan..ial thromboplastin time (1YrI). Her CBC shows a hemoglobin couccntralion of 12.7 gfdL, hemalocril of 37.1%. MCV of 80 fiJred ccll, platelel eoUO! of 276'<XlOfpL. aOO WBC count of 56OCV¡..¡.L. Htt templalc b1ceding time is 3 minules. Her fibrinogen leve! is normal. aOO no fibrin splil produets are delec1ablc. Which 01' lhe following eondilions best explains thcse findings'!

O O O O O

(A) (B) (C) (O) (E)

Macronodular cirmosis Chronic renal failurc Meningococcemia Vilamin C deliciency Melastalic cllrdnoll1a

8. Blood culture in a 30-year-old male Wilh hypotension aud shock is positivc for KlebsieJltl /melllllot/ille. Scaucred ecchymoses are scen over his trunk and extremilies. 1lle appearance of his RBC.. in a periphernl blood ~mear is shown in the following figure. These findings are most indicative of which of the following condilions?

Courlesy oí Dr. Robe" W. r.1cKenlla. Dcpar'll1l('nl 01 p..llholoI1Y. UIll\"cr5!ly of T"'KII.~ SwlhwcSlem Medien! School. 0;\11,,-,. TX.

O (A) Heredilmy spherocytosis O (B) AuloimmullC hemolylic anemia O (e) Microangiopathic hemolylic anemia O (O) lron deficiency anemia O (E) Megalobla<;lic anemia 9. A 29-year-old female who has nercdilary spheroc)'tosis and mild anemia ha>; devcloped a low+grade fever with malaise. Afier a wcck. she f«ls very lired and appears pale. Her hemalocrit drops from the usual value of 36q. 10 28%. TIlere is no change io lhe appearance of red «11 morphology. ReliculocYlcs are a~nt from lhe periphernl blood. Her sel'Um bi1irubin is wilhin ¡he referencc range. Which of Ihe following events has mosl likely occurrcd'!

O O O O O

(A) (B) (C) (O) (E)

Developmcnt of anli-red ccll antibodies Oisseminatcd inlravascular coaguJopalhy Aceeleraled exlrava...cular hemolysis in the spleen Reduccd erythropoiesis I'rom parvovirus infl:clion Superimposed iron deficicncy

10. A 60-year-old male who has tcnninal carcinoma of the oolon dc"clops widcsprcad ccehymoscs over his skin surface. The PT is 30 seconds. P'rJ' i~ 55 scconds. platclet count is 15.2OClIpL fibrinogeo levcl is 75 mgldL. and fibrin split produel Ic"els are very clcvaled. Which of lhe following morphologic findings would yoo mffil expec1 10 liOO on examinatiOIl of lhe peripheral blood smear?

O (A) Howell-Jolly bodies O (B) Tcar-drop eclls O (C) Macro-ovalocylCs

O (O) SchislOCYICS O (E) Targel cclls 11. A 30-year-old female has a cae demonstrating a hemoglobin concenlral.ion of 11.8 gldL and hemalocril of 35.1 %. The periphcral blood smear show~ mal spheroc)'les and rare nucleatcd RBCs are presento The direct and


Chopler 13

indirect Coombs tests are positive at 37"e. although not at 4"e. She has mi Id splenomcgaly. Which of lhe following underlying diseases is she mast likely to have?

O (A) Infcctious mooonucleosis O (8) M)'coplasma pneumoniae infccliofl O (O Hereditary spberocytasis O (O) EscJU!ricllia coli septicemia O (E) Systemic lupus erythematasus (SLE) 12. A )'oung adult palient has juSi been diagnosed wilh VOl1 Willebrand disease. Which of the following statements should you make to advise the palient of potential consequences of Ihis disease? O (A) You lllay nced an allogeneic bone lllaITOW lransplant. O (8) Expect increasing difficulties wilh joim lllobility. O (e) Anticoagulation is needed to prevent deep venous throlllbosis. O (O) You lllay have excessive bleeding following tooth extraction. O (E) A splenectolllY may be necessary to conlrol the disease. 13. Hydroxyurea therapy has boen found to be beneficial in p3lients wilh sicide cell anemia. 1ñe basis for its therapeutic efficacy is O O O O O

(A) (B) (e) (O) (E)

An increase in the pnxIuction of hemoglobin F An increase in the produaion of hemoglobin A A decrease in overall globin synthesis A stimulation of erylhrocyte productioll An increase in the oxygcn affinity of hemoglobin

14. A 73-year-old male who is taking no medicatiortS aOO has been healthy all his life. with no majar illnesses OT surgeries. is becoming increasingly tired and Iistless. A eBe indicates a hemoglobin concentration of 9.7 g/dL, hemalocril of 29.9%. MCV of 69.7 tllred cell. RBC count of 4.28 X 1000/J,tL. platelet count of 331.000/p.L. and WBC count of 55001 J,tL. The most prob.., ble explanalion for these lindings is O O O O O

(A) (8) (e) (O) (E)

lron deficiency Autoimmune hemolytic anemia j3-lhalassemia major Otronic alcoholism Vitamin 13 12 deficiency

15. 1bree days after taking nn anti-inflammalory medication that illdudes phenacetin. a 23-year-old African-Arnerican maJe passes dart:: reddish-brown urinc. He is surprised by this. bccause he has been heallhy all his Jife. wilh no majar illnesscs. A cac delnonstmtes a mild normocytic anemia, but the peripheral blood smear shows prccipilate5 of denalured glOOin (i.e.• Heinz bodies) with supravital stainillg and scatlered "'bite ceUs" in the population of RBCs. These findings are masl typical far O O O O O

(A) a-Ihalassemia (O) SickJe cell tmil (e) Glucose-6-phosphate dehydrogenase deficiellcy (D) Auloimmune hemolytic anemia (E) {3-thalassemia minar

RED CELLS AND BlEEDING DISORDERS

125

16. A 50-year-old maJe who presents with chroruc fatigue with weight loss is foun<! lO have a helnoglOOin concentration of 11.2 gldL. hematocrit of 33.3%. MCV of 91 flJred ceU. platelet coont of 240,()()(Vp.L, and WBC oount of 755G'J,tL. He has a serum iron of 80 ¡.t.g/dL, lotal ¡ronbinding capacity of 145 ~g/dL, and serum ferritin of 565 nglmL 1bese findings are most indicative of O O O O O

(A) lron deficieocy anemia (B) Aplastic anemia (O Anemia of chronic disease (O) Microangiopathic hemclytic anemia (E) Megaloblastic anemia

17. Which of the following infectiOlls agenls accounts for lhe observed distribulion of hemoglobin S in human populations? O (A) Cryptococcus neofonnalls O (O) Borrelia burgdoiferi O (e) Treponema pallidum O (O) P/asmodillt1l falciparum O (E) C/ostridill1n peifringens

18. A 41-year-old remale presents with a 2-week history of multiple ecchyrnoses on extremities wilh only minar trauma. She also feels extremely \\'eak. Over lhe past day she has developed a seVefe cough produetive of yellowish sputum. She has the followillg COC findings: hemoglOOin ooncentralion of 7.2 g/dI.., hematocrit of 21.4%. MCV of 88 f1Jred cell. platelet count of 35.<XXVJLI..., and WBC count of 14OOIJLI..., wilh 20 segmellled neutrophils. I band, 66 Iymphocytes. aOO 13 lnooocytes. Reliculoc)'tosis is absenL Given these laboratory findings. which or the follo\\'· ing potnts in the history \\'ould be mast useful in detennining Ihe cause of her condition? O O O O O

(A) (B) (e) (D) (E)

Hislory of exposure to drugs Dietary history History of recent bacterial infectioll Menstrual history Family history of anemias

19. A 40-year-old male who suffered from chronic anemia since childhood was admiued to the hospital wiln fever aOO pain in the chest. Despite supportive thernpy he died a few days later. A small. fibrotic. 5-g spleen filie<! with deposits of iron and calcium is fouOO at autopsy. Which of lhe following coOOitions is mast likely to nave resulled in Ihis finding? O O O O O

(A) Sicide cell anemia (B) ~Ihalassemia (e) Malaria (O) Idiopathic lhromboc)1ope.nic purpura (JTP) (E) Autoimmune hemolytic anemia

20. A 13-year-old male has les... lhan 1% factor VIII activity lneasured in plasma. Ir he does noe receive transfusions of factor VIII concentrale. which of Ihe following manifestation... of this deficieney is most likely lo ensue? O (A) Splenomegaly O (13) COlljullctival petechiae


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o (e)

Hemolysis

O (E)

I-Iemarthroses

O (O) Hemochromatosis

21. A 23-year-old female was in her 251h week of pregnancy when she ceased lo feel fetal rnovement. Thrce weeks laler, she has slill nOl delivcred. but she suddenly dcvelops dyspnea with cyanosis and is found lo be hypolensive. She has large ecchymoses over her ski n and melena. She is found 10 have an elevated PT and prr. The platelel COUIll is decreased. Her plasma fibrinogen is markedly decreased, and fibrin splil produets are dclceled. The mosl likely cause of her blecding dimhesis i~

O O O O

(A) Incrcased vascular fragilily (B) Toxic injury lO Ihe cndOlhelium (e) Reduced production of platelels (O) Increased consumplion oC c10tting Cacton; and plalelets O (E) Defects in plalelel adhesion and aggregation For each of Ihe clinical hiSlories in questions 22 Ihrough 24, selecl lhe mosl c10sely associaled leUcrL~ mcchanism for developrncllI of anemia:

O (A) Mechanical fragmemmion of RBCs O (B) Lncreao;ed susceplibilily to Iysis by cornplemem O (C) Nuclear malumtion defects due 10 impaired ONA

synthesis

O (O) Impaired globin synthesis

-

O (E) Hemolysis of antibody...c;ooled cclls

O (F) Slcm ccll defecl O (G) Oxidative illjury lO hemoglobin O (H) Reduced deformabililY 01" Ihe red cell membralle

O (1) ProducliOIl of an abnorrnal hernoglobin O (1) 1mbalance in Ihe symhesis of a- and ,B-globin chains

COllrtesy of Dr. R.>bcn W. MeKenn:l. Dt.'J1<'nH>e111 uf Palhology. Univcrsily oí Texas Suulhl"cslcm School. D:.U.. s, TX-

25. A 12-year-old male experienced lhe sudden onset of severe abdominal pain and cramping. 111e peripheral blood smear shown in Ihe figures is mosl suggeslive of which of lhe following RBC disorden;?

22. A baby is born al 34 weeks' geslalion lO a gravida 3 para 2 female who is 28 years old. The baby is markcdly hydropic and iCleric. A cord blood samplc is laken, and thc direcl Coombs Iesl result is positi\'e for Ihe baby's R8es. ( )

O (A) Heredilary spherocylosis O (8) a-Ihalassemia O (e) Paroxysmal nOClurnal hemoglobinuria O (D) Hcmoglobin C disease

23. A 30-year-old male passcs dark brown urille several days afler slmting lhe prophylactic anlimalarial drug prinmquinc. His serum haploglobin concenlration lS dccrcased. ( )

26. Patients who inherit mulalions lhal reduce lhc level oC spcclrin in Ihe red cel1 membrane cyloskeleton develop a chronic anemia wilh splenomeg.dy. In Illany such pmiellls, splenectomy reduces Ihe severily of allemia. This beneficial effect of splellcclomy is related to which of Ihe following processes?

24. A 62-year-old malc presents to lhe emergency deparlrnelll in an obvious stale of inebriaúon. He is known in Ihe emergency dep..'U"tmem because Ihis scenario has repemed itselF many times Ihroughout the ycars. A CBC is ordcred, which shows anemia (hemoglobin level of 8.2 gldL), with a very high MCV (115 filrcd eell), Ihrombocylopcnia, and nculropenia. Microscopic examinalion of Ihe peripheml blood shows prominenl anisocylosis, including very large red cells. Polychromalophilic red cells arc difficult lo find. A few of lhe neulrophils demonslrale six. lO seven nuclear lobcs. ( )

O (E) Sickle cell anemia

O O O O O

(A) An increase in Ihe synlhesis of speclrin in RBC (B) An increase in Ihe dcforrnabilily of red eells (C) A dccrease in Ihe opsonizalion of red cells (O) A dccrcase in lhc lrapping of red cells in Ihe spleen (E) A decrease in Ihe produclion of reaclive oxygen spccies

27. A 39-year-old female presented Wilh a 3-monlh his10ry of abdominal pain and intermitlenl dianhea. Further radiologic examinalion and colonoscopy eslablished lhe di-


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agnosis of Crohn's disea<>e. Because she failed 10 respond to medical therapy. part of lhe colon and lerminal ileum ..vere surgically remo\'ed. She was lransfused wilh I unit of packed RBCs during surger)'. Se\'ernl weeks laler, sbe is apparently healtby bul complains of easy faligabilit)'. On in\'estigalioll. she is found lO ha...e lhe following cnc findings: bemoglobin concenlralion of 10.6 g/dL, hematocrit of 31.6%. RBC count of 2.69 millionJ¡.LL, MCV of 118 fUred cell. platelel eounl of 378,000I¡.LL. and WBC eount of 980ll'p.L. The mosl likely eondition Ihal explains lhese findings is O (A) Post-blood Imnsfusioll hemolytic anemia O (8) Tron deficiency O (e) Chronic blood loss

O (O) Vitamin B12 deficiency O (E) Anemia of chmnic disease

28. A 45-year-(lld maJe with E. coli septicemia beconleS hypotensivf: and requires increasing pressor support to mainlain bJood pressure. He de...elops a guaiae-positi...e slOol and ecchymoses of the skin. A CBC shows tbat the hemoglobin ooncenlration is 9.2 gldL aud hematocrit is 28.1 %. Platelet counl is reduced 10 70.()(x)/¡.LL. Increased amourlls of fibrin split products are identilied in the bJood. Which of the following conditions is mOSI Iikely responsible fOl" Ihe low hemmocril?

O (A) Warm auloillllllune hemolylic anemia O (8) P'd.roxyslIlal noclurnal hernoglobinuria O (C) Mjcroangiopalhic hemolytic anemia O (O) ~thalassemia major O (E) Aplas'ie anemia

29. A Io-year-(lld child with homozygous siekle cel! anemia had multiple episodes of pneumOlua aOO meningilis wilh septicemia. 1ñe causative organisms cultured included S/reprococclIs pnellmonille and HlIemop/¡illls illjfllen¡Pi'. Qne final episode of meningitis resulted in lhe dealh of Ihe child. 11le mosl likely cause of repealed i,úectiollS in Ihis ease is

O (A) Loss of Ilomml splellic fUllctioll from reCUlTenl ischemic injury 0(8) Reduced SYlllhesis of immulloglobuJiIlS O (e) lmpaired neutrophil produclion O (O) Reduced sYJlthesis of complemem proIeins by the liver O (E) Reduced expression of adhesion molecules on erKJolllelial cells 30. A beallhy 19-year-old female suffered blunt abdominal trauma in a motor vehicle accidento On admissioo lO Ihe hospital, her inilial hematocrit was 33%, but over the nexl hour. it dropped lO 28%. A paracentesis yielded serosanguineous fluid. She was laken 10 surgery, where a liver laceration was repaired alld a liter of bloody fluid was removed. fram Ihe peritoneal cavilY. Her condilion remained. slable. A C8C performed 3 days later is masl likely lO derl'lOllSlrale which of the following morphologic findings in R8Cs in Ihe periphern.1 blood?

O (A) RelicuJOC)1osis O (8) Leukoerythmblaslosis

RED CELLS AND SlEEDING DISORDERS

127

O (C) Basophilic stippling O (O) Hypochromia O (E) SchistocYlcs 31.

Which of tlle following parameters reported (rom a indication of rnaLTOC)'tosis?

enc can provide an

O (A) Mean corpuscular volume (MCV) O (8) Mean corpuscular hemoglobin (MCH) O (O Mean

corpuscular hemoglobin (MCHC) O (D) Red cell dislriblllion widlh (ROW) O (E) Helllalocril

concenlration

32. A 17-year-(lld maJe presents with passage of dari< urine. He ha<> had muhiple bacterial ilúectioos over several )'ears aOO has a history of venous Ihromboses. iocJuding portal ''ein thrombosis in the previous )'e'dr. A CBC shows a herl'lOglobin concenlration of 9.8 g/di.., hematocril of 29.9%. MCV of 92 fUred ceH. plalelet COUIlt of 150,0fXV pl., and WBC coum of 38001p.1.., wilh a differenlial coum of 24 segmented neulrophils. I band. 64 lymphoC)'tes. 10 monoc)'tes. aOO I eosinophil. He has a reliC\llocylosis. l11e serum haptoglobin level is ve!)' low. A mUlatioll in which of Ihe following gene products could give rise to Ihis clinicaJ condition? O (A) SpeL1.rin

O (8) Glucose-6-phosphate dehydrogenao;e O (O Phosphatidylinositol glycan A (pIGA)

O (O)

~globin

chain

O CE) Factor V 33. A 32-year-old maJe has had a chronic anemia for mallY years. Alpha-globin illclusiollS are presem in e1)'throblaslS and erylhrocytes. leading to increased pIlagocylosis by cells of lhe mononuclear phagoc)'le s)'stem. The result is ineffecti"e bematopoiesis and increased absorplion of dielary iron leading 10 hemochromatosis. These findings are masl Iypical for

O (A) 0(8) O (e) O (O) O (E)

AUlOimmune hemoJytic anemia GJucose-6-phosphale dehydrogenase deficiency Megaloblasllc anemia IHhalassemia Sickle cell anemia

For each paliem described in qUestiOflS 34 Ihrough J7. select the mosl likely underlying cause of bleeding:

O (A) Hemophilia A O (B) Hemophilia A with inhibilOrS of factor VIU O (e) Vitamin K deficieoc)' O (O) voo Willebrand disease O (E) Heparin lherapy O (f) Idiopalhic Ihrombocytopenic purpum (ITP) O (G) Disseminated intravascular coagulatioll O (H) lhrombotic Ihrombocytopenic purpura (TTP) O (1) Coumadin therapy 34. A 13-year-old child has a hislory of bleeding, includillg severe hemonhage into the knec joilll, requiring multipie transfusions. Other male members of lhe family have bleedillg JrOblems. He has a proIonged PlT and a normal


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DISEASES OF ORGAN SYSTEMS

PT (PT). A 1:1 dilution of patient's pla~ma with normal pooled plasma does 001 correet the ITJT. ( )

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35. A 16-)'ear-old male has a hislory of easy bruising and hemorrhages into lhe knee joint lhal ha\'e led to joinl defomlity. Other maJe members of lhe family ha\'e also had bleeding problems. He has a prolonged PlT and a normal PT. Al: I dilution of lhis palienl's plasma with normal pooled p1a... ma correclS the VIT. ( )

41. A 7-year-old African+American male ctlild koown tO be sulTering from sickle cell anemia presents with severe rain in Ihe bones of the right hand. There is no associated fever or IeukocYIOSis. 1ñe most likely pathogenetic fador in lile causalion of this pain is

36. A 23-year-old female has had a history of bleeding

e e

problems all of her life, primanly heavy menstrum.ion and gum bleeding. A sisler and an uncle have similar problems. Bleeding time is prolonged. Her VI' is nonnal. and the PTr is mildly prolonged, bul il corrects wilh al: I dilulion Wilh normal pooled plasma. Factor VIII aetivilY is 30% (reference range, 50'itl to 150%). Her platelel count is within referellce range. ( ) 37. A 42-year-old female presems wilh a several-month hislory of nose bleed~, easy bruisillg, and increased bleeding Wilh her menslrual perioos. There are no other symptoms or siglls. Physical examinaliOIl reveals scattered peteehiae over her distal exlremities. lñe peripheral blood smear shows a decrease in plalelets an<! nonnal red blood cell morphology. Examinalion of lhe bone maITQW biopsy shows a marked inerease in megakaryocYles. Her PT aOO ITJT values are wilhin lhe refm=nce range. ( ) 38. A 3-year-old child of Ilalian anceslry presents with failure lO Ihri\'e. Physical examination shows hepatosplenomegaly. Hil: hemoglobin concentralion is 6 gldL, and the peripheral blood smear reveals severely hypochromic microc:ytic red cells. Total .serum iron le\'el is normal. 1ñe ret:iculocyle coont is 10%, Hemoglobill e1eetrophoresis reveals \'ery Hule hemoglobin A. A radiogmph of the skull shows maxillofacial defonnities. The principal cause of anemia and other abnonnalities in Ihis patienl is

O (A) Reduce<! synthesis of hemoglobin F O (8) Reduced red blood cell sUl"\'i\'al fmm imbalanee in

the pro<1uclion of 0'- alld J3-g1obin chains O (C) Se<lueslration of the iron in lhe reliculoendolhelial eeJls O (D) Inerease<! fragility of lbe erythrocytc membrane O (E) Relative deficieney of vitamin 8 n 39. Worldwide.!he most common cause for impaired red blood cell production lending lo anemia is O (A) Th..i1~mia O (B) lron deticiency

O O

(C) Chronic infection (O) Mela'itatic carcinoma O (E) Toxic marro\\' injury

40. Your 55-year-old male patient has anemia bul no signiflcanl pas! medical or surgical hiSlory. He eurrently feels tine. except for SQme minor faligue wilh exenion. You are asked lO delennine lhe adequaey of his total body iron stares. What is the mQSt sensili\'e an<! cosl-effeeli\'e lel>l that you should order?

O (A) Serum iron O (B) Serum transferrin

(C) Hemoglobin (O) Bone marrow biopsy O (E) Serum ferritin

e e e

(A) Oefects in the allemalive complemenl palhway (B) Increased adhesion of red blood cell.~ tn lhe endothelium (C) Erosioo of bones from slimulation of erythropoiesis (O) Increased red blood cell sickling in lhe peripher.l.l tissues (E) Inerea<;ed produclion of fetal hemoglobin

42. A 78-year-old m¡¡le presel1ls wilh worsellillg malaise ¡md fatigue over the past 5 monlhs. He also ha:,: an ellI¡¡rged spleell. His CBC shows a hemoglobin concentralion of 10.6 g/dL. hematocril of 29.8%. MCV ol' 92 tVred ceH. platelel count of 95.000I~L. and WBC count of 49OlY~uL. The WBC differential count shows 67 segmented neUlrophils. 4 bands. 2 melamyelocytes, 22 lympOOcytes. 5 mono.. cytes. and 3 nucleated RBCs per 100 WBCs. The peripheral blood smear shows occa"lonal tear--drop ceUs. An examinalion of bone marrow biopsy and smear is most likely tO show

e

(A) Marrow packed wilh myeloblasts

e e e

reduced hematopoietic islands (C) Replaeemenl of marrow by fal (O) Presence of nUllleTOUS megaloblasls (E) Marked nonnoblastic ery1.hroid hyperplasia

O (B) Marrow tibrosis wilh greatly

43. In your workup of a 5o...year-old malc- wilh anemia, )'OU are asked lO arder tests for vilamin 8 12 and folate. Whal is the mast importam reason for ordering fhe lests for lhese nUlrients simultaneously?

e (A) e (B) e (C) e (O) e (E)

They are bolh absorbed similarly. Therapy for one also lreals the mher. The peripheral blood smear appears lhe same for boIh. Aplastic anemia may result from lack of either. Neurologic injury musl be a\'oided.

44. A hemoglobin electropl'JOresis is petfonned on the R8Cs of a 26-year-old African-American male undergoing a workup of chronic anemia It sllows lila!. almost all of the hemoglobin present is hemogIobin S. In lhis palient, yoo woold moSI expea. to find which of the fol1owing complicallons of his underlying disease?

e e e e e

(A) Miaonodular cirrbosis (B) Chronic atrophic gastritis (C) Pigment gallstones (O) A high rale of stillbirths in his family (E) An esophageal ",eb

45. A 42-year-old maje hospitalized with K. Im€WlIolliae seplicemia was observed over the course of 2 days to have deereasing renal aOO hepalie function. He was bleeding fram Ihe endolracheal tube and rrOIll his Foley catheter.


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His condition conlinued lO worsen, with hypotension and shock. and he died. At autopsy. microthrombi are found in anerioles aOO capillaries of lhe kidneys, adrenals. brain, and li\'er. Which of the foUowing laboralory tesl resulls obmined during his lenninal course is most charncteristic for his condition?

o (G)

REO CEliS ANO BlfEDIF'-K; DISOOOERS

129

Allemia of chronic disease

O (H) lron defidenc)' anemia O (t) Paroxysmal nocturnal hemoglobinuria O (J) Thrombotic thromboc)'topenic purpura (ITP) O (K) Disseminated imravascular coagulation

O (L) Acule b100d loss

O (A) Increased bleeding lime O (B) Ele\'ated fibrin split products

O (C) Deficiency of von Wi/lebraOO factor O (O) Increased plasma fibrinogen O (E) Thrombocylosis

46. A 40-year-old maJe died from congesti\'e heart failure complicated by arrhythmias. At autopsy. the heart is darli. brown alld enlarged. wilh thickened ventricular walls and slighl chamber dilation. llle li\'er has a micronodular pattero of cirrhosis aOO appears dark brown. The myocardium and lhe Iiver centain extensive iran depos.ition as scen with the Prussian blue stain. Which of lhe following inherited RBC disordef"S is he mosI likely to have?

O (A) ,B-thalassemia majar O (B) Heredilary spllerQC}'toois O (C) Sickle cell anemia O (O) Glu{;ose-6-phosphale dehydrogenase deficiency O (E) ,B-Ihalassemia minor 47. A 31-year-old maJe has a history 01' chronic anemia and painful crises Wilh joinl and abdominal pajo. A head compuled tomography sean reveals severa! small remole infarclions. During one of these acute crises. he is admitted with severe dyspnea A CBC is performed Which of lhe following morphologic findings for RBCs is most Iikely lO be seen on the peripheral blood smear? O (A) Tear-drop cells O (8) Sickle cells O (C) Schisloc}'tosis O (O) Microcytosis O (E) Spherocytosis

49. A 45-year.-old lemale has a long history of rneumaloid arthritis. A CBC reveals the foUowing: hemoglobin concentmlion of 11.6 g/dL. hemalocril of 34.8%. MCV of 87 fl.Jred ceU. plalelet count of 268.000IILL. and WBC count of 68OCY.uL. The serum haptoglobin leve! is nonnal, and the serum iron concentnllion is 20 ¡ugldL; total ironbinding capadty is 195 J.LgfdL. and the percent saturntion is 10.2. 11le serum femtin concentrcl.tioll is 317 ng/rnL. No fibrin split products are delected. lOe reticuloc}1e concentration is 1.1%. 50. A 54-year.-old female presents with the sudden onset of headaches with pllOtophobia worsening for the pasl 2 days. She has a tempemlure of 37"'C. A CBC shows lhe following: hemoglobin concentrntion of 11.2 gldL, hematocrit of 33.7%, MCV 94 of fl.Jred cell, platelet count of 32.lJOt)I.uL, and WBC count of 99OCV.uL. The peripheml blood smear demollstrates schistocyles. Her serum urea nitrogen level is 38 mg/dL, and the crealinine concentrdtion is 3.9 mg/dL. 51. A 65-year.-old male presellts with increasing fatigue. alld a CSC shows lhe following; hemoglobin concentrcl.tion of 5.9 gldL, hematocrit of 17.3%. MCV of 96 flJred cel!. platelet count of 150.()()}I.uL, and WBC count of 78OOi1Ú1ñe miculoC}1e concentration is increased at 29%. No fibrin split produetS are delcclod. aOO the direct and indirect Coombs test results are negalive. Bolle marrow demOl\stroles marked erythroid hyperplasia. Which of the following conditiOllS best explains these findings? O (A) 8100d loss

48. A diagnosis of systemic lupus erylhemnlosus (SLE) is made in a 61-year-old male who has anemia wilh a hematocril of 24%. A urillalysis dipstick examination reveals lhe presence 0'- blood, but (here are no WBCs, RBCo;, or casts on lhe urine microscopic examil\ation. A hemol),tic anemia is suspected. Which of the following serum labormory lest tindings woold best conoborate this diagnosis? O (A) Elevated d-Dimer O (8) Negative Coombs atlliglobulin test

O (C) Decreased iron O (O) Elevated antinuclear antibOOy tiler O (E) Diminished haptoglobill For each of the patiem histories in questions 49 and 50. match the most c10sely associated hemalologic condition tilm can cause anemia:

O O O O O O

(A) Idiopa(hic Ihromboc)'topenic purpura (ITP) (B) Wann aUloimmUlle hemolytic anemia (C) ,B-lhalassemia major (O) a-thalassemia mujer (E) Sickle cell anemia (F) Hereditary spheroc}1osis

O (B) lron deficiency O (C) Aplastic anemia

O (O) Metaslatic carcinoma O (E) Immunohemolytic anemia

ANSWERS 1. (C) This patient's blccding is cause<! by a low p1atelet: counl. She most likely has idiopathic thrombocytopenic purpuro (ITP). in which platelets are destroyed in Ihe spleen after being coaled wilh an antiplatelet antibody. The serum conlains alllipllltelet antibodies that presumably coat Ihe patient's platelets and Ihe transfused plalelets. Because spleen is the source of the antibOOy and the site of deslruction, splenectomy can be beneficia!. There is no defect in the prodoction of platelets. Suppression of pluripotent stero ceJls gives rise to aplastic anemia in which there is pancytopenia Plalelet fullClions are nonnal wilh ITP.

BP6 387 PBD6 634-636


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DISEASES OF ORGAN SYSTEMS

2. (B) She has cold alllllutinin disea...e with anlibody (usually 11lM) coatinll RBCs. Tñe 11lM a.lllibodies bind lo the red cells al low leOlperature a.l1d fix complement. However, coOlplemeO! is 001 Iytic al this leOlperature. Wilh a rise in temperature, lhe IgM is dissociated from IOC cel!. leaving behind C3b. Most of lhe hemol}'sis occurs extra· vascularl}' in the cells of lhe mooonuclear phagoc}1e s}'slem, such as Kupffer cells in lhe Iiver, because of lhe coating of complemenl C3b thal acts as an opsonin. Raynaud phenomcnon occurs in exposed. colder arcas of lhe body such as fingers and loes. She probably has an elevaled cold agglutinin liler. IgE is prescnt wilh aJlergic condilions, and histamine is rc1eased wilh Iype 1 hypersensilivity reaetions. ¡gG is Iypically involved in warm anlibody hemolytie anemia. lñe anemia is chronic and is oot triggered by cold. Fibronectin is an adhesive cell surface glycoprotein that aids in lissue healing.

BP6351

PBD6 620-621

3. (e) Many of !he c101tin!,! faetors tJ131 are instrumenlal in Ihe in vitrO measureme.lll of the extrinsic palh"oay of coogulation, as measured by lhe Pr, are synthesized in me Iiver. voo Willebrand factor is made by endothelial cells, .1101 hepatocytes. llle plalc1el couo! is not direetly affected by liver disea-.e. lncreased fibrin splil prodUcls SUllgesl a consumptive coagulopalhy such as disseminaled il1lravascular coogulalion (DIC). 111e bleeding time is a measure of plalelel funclion, which is not signilicantl)' <lffectcd by I¡ver dise<lse.

BP6 384 PBD6 633 4. (B) Although ~thalassemia minor aOO iron deficiency anemia have hypochromic aOO microcYlic RBCs. there is no increase in hemoglobin A 2 in iron deficiency states. Normal serum ferritin also excludes iron deficiency_ Unlike {3-lhalassemia major. lhere is usually JUSI a mild anemia Wililoul majar organ d)'sfunclKm. Diseases lhat produce hemolysis aOO increase erylhropoiesis (e.g.. autoimmune hemolYlic anemia, maJan<l) do nOl aller the compositiol1 of ~globin chain production. Anemia of chronic discase may mimic iron deficiency and Ihalassemia minor wilh respecl lO hYIx>chromi<l and microcytosis. However, il is associaled wilh an increasc in Ihe serum concentralion of ferritin.

BP6350 PBD6 617 -61 B 5. (8) Specrrin and related proteins (e.g.. protein 4.1, ankyrin) are cytoskeletal proIeins thal are importanl in maintaining the RBC sl1ape. Hereditary spheroc)1osis is a coodition in which a mutalion affects oue of several membrane C)'loskeletal proIeins. 1llese mutations serondarily reduce spectrin synthesis even if lhe spectrin gene is normal. Spectrin-deficient RBCs are less deformable. -nle abnormal RI3Cs appear lO lack central pallor on <l peripheral blood SOlear, aOO lhey are sequestered aOO destroyed in lhe spleen. Glucosc-6-phosphme dehydrogenase deficiency is an X-linked cOlldilion mosl commollly affecling black males. '1113lassemias wilh ahnormal a- or t3-lllobin chains are associaled wilh hypochromic microcytic anemias.

BP6343-344 PBD6 607-609 6. (8) -me RBCs display hypochromia and microcytosis, consislenl with iron deficiency. 11le mosl common cause for this in older peTSOns is chronic blood loss, aOO a gas-

troinlestinal source (e.g., carcinoma, ulcer disease) should be soughl. Al age 69 she is nOl mel1struating, aOO vaginal bleeding is likely lO be noticed aOO is a "red nag" for a g}'neooI01lic malignancy. Pemicious anemia fTom vilamin Bll deficiency should result in a macrocytic anemia llle RBCs are generall)' normocytic with aplastic anemia Microcytosis may accompany thalassemias. bUI she would be unlikely to live lO age 69 with t3-lhalassemia majar. AUloimmune hemolytic anemias usuall)' produce a nomloc}'1ic anemia, or lhe MCV can be slighlly elevme<! with a brisk reliculocytosis.

BP6353-354

PBD6 629-630

7. (D) Plalelet Ilumber and funccion in Ihis case are normal, aOO Ihere ¡s no detectable abllonnalily in the eXlrinsic or intrinsic plltItways of coagulatioll as measured by lile PT or PlT. Pelechia aOO ecchymoses can result from increase<1 vascular frngility. a conseque.nce of nUlritiona! deficiency (e.g., vitamin C). infectioo (e.g.• meningococcemia), and vasculitic disea.~. Meningococcemia is an acule iIIness. Uver distase should affect lhe P'T. Chronic renal failure may depres... plmelel function. Melaslalic disease does IlOl direclly affec1 hemoslasis, allhough exlensive marrow mela..tases could diminish platelet procluclion.

BP6384

PBD6 634-635

8. (C) The fTllgmenled RBCs, including "helmet cells," are typical for condilions Ihal c.'1n produce a microangiopathic hemolytic anemia, sueh as DIC. Tri>, SLE, hell'loIytic-uremic syndroll'le (HUS), and malignant hypenension. Such fragmeIltcd RBCs can be called schislocytes. SplleTOC}1es may Ix' prescnt wilh hereditary spllerocYlosis. bul lhe RBC destruction is eXlravasaJlar, and fragmented RBCs do llOI appear in lhe peripheral blood. In auloimmune hemoI)'tic anemia, the hemolysis is extravascular as well. aOO spheroq1es may be fonned. "I1lere may be marl;ed anisoC}1osis and poikilocytosis Wilh iron deficiency and wilh megaloblastic anemias_ but fragmentation of RBCs is .1101 seen.

BP6 352 PBD6 621. 640 9. (D) ll1is plllient has aplastic crisis. precipiltlted by a p.'1T\'ovirus infecliOIl. In adults who do nol have a defect in l"Ionna1 RBC production such as heredilllry splleroc)1osis or sickle cell anemia or who are nol inunullosuppressed, par\'()\'irus infection is self-limiled aOO often goes unnoliced. When RBC produetion is s.ml oown wilh paT\'ovirus. lhere is no reliculoc}1OSis. Accelerated red cell destruaion in the srleen would be expected to cause a rise in serum bilirubino DIC gives rise lO thromboc)1openia, bleeding, aOO lhe appearance of fragmented red cells in lhe blood smear. lron deficiency does nOl occur in hemolytic anemias because lhe imn releac;ed from henlOl)"l.ed cells is reused.

PBD6 609 10. (D) This is al1 example or a DIC wilh associmed microallgiopalhic hemolYlic anemill. llle DIC devc10ped in Ihe selting of a lllucin-secreting adcnocnrcinoma. HowellJoUy bodies are sm<ll1, rouOO incJusions in RBCs that appear when the spleen is absenl. Tear-drop cells are IllOs1 characteriSlic for myelofibrn<;is aOO olher infiltrati\'e disorders of the marrow. Macro-ovalocyres are seen with megaloblastic anemias, such as vilamin Bl l deficiency. Tar·


Chopfer 13

get cells appear when lhere is hemoglobin severe liver disease.

e disease

or

8P6343 POD6 640-642, 685 J l. (E) She has a wann autoimmune hemol)1ic anemia A positive Coombs lest indicales (he presence of anti~RBC anlibodies in the serum aOO on the red cell surface. Most cases of warm auloimmune hemol)'tic anemia are idiopalhic. bUI one fourth occur in persons \\'ith an identifiable autoimmune disease such as SLE. Some are cause<! by drugs such as a-mel.hyldopa. The immunoglobulin coating the RBCs aets as an opsonin (O prolllOle splenic phagocylosis. Nucleated RBCs can be seen with active hemolysis. because lhe marrow compensates by releasing irnmature RBCs. Infections such as mononucleosis and M)'coplasma are assacimed wilh cold autoimmune hemolytic anemia (wilh an e1evated cold agglulinin titer). Septicemia is more likely lo lead lO a microlmgiopalhic hemolytic anemia. The increased Rac deslruction wilh hereditary spherocylosis is exlrav<lscular and nol immune medi<lled.

8P6 351

P8D6 620-621

12. (D) ln most cases of von WillebraOO disease. there is a diminished amounl of circulating \'on Willebrand factor. which is necessary for proper platelet adhesion, aOO affected persons have a mild bleeding lendellCY. Because lhe disease is nol a disorder of stem ceUs. transplanlation is not helpful. Joint hemonhages are a feature of hemophilia A aOO B, nol VOl1 WiUebraOO disease. Palients with von WillebraOO disease are nol prone lo lhrombosis. as are persans wilh factor V Le1den mutalion or other inheriled disorders of anticoagularion. Spleneclomy is useful in cases of ITP. bUl the plalelets are not consumed in von Willebrand disease. 8P6 388-389 P8D6 638-639 13. (A) In ¡Kiulls wilh sickle celJ anemia, hydroxyurea inereases hemoglobin F production, which inhibits the ¡XlIymerization of hemoglobin S. Bec<luse hemoglobin F levels are high for Ihe firsl 5 lO 6 months of life, patients with sickle cell anemia do nol manifest the disease durillg this periodo Globin s)'lllhesis decreases with Ihe Ihlllassemia<;. The hemolysis associated wilh siclding promotes erythropoiesis, huI lhe concelltralion of hemoglobin S is not changa!. H)'drox)'urea does not shifl lhe oxygen dissociation curve nor change lhe ox)'gen affinity of lhe various hemoglobins.

P8D6612 14. (A) This man has a microc)1ic anemia. which is lypical for iron deficieney. Al his age, bleeding from an OCcull malignaney should be slJOngl)' SUSpecled as Ihe cause of iron deficiency. An aUloirnmune hemol)1ic anemia should appear as a normocytic anemia or wilh a slightly íocreased MCV wilh pronouoced reticulOC)1osis. 1ñalassemias may resull in a micTOC)1osis. but .f3-thalassemia major causes severe anemia SOOIl afier birth, and survival lo lhe age of 73 years is unlikely. Macrocytosis should accompan), a history of chronic alcoholism, probllbl)' because of pool" diet and folate deficienc)'_ 8 12 deficiellCY also results in a ll1acrocytic anemia.

8P6 353 P8D6 627 -629

RED CEUS AND BlEED1NG DISORDERS

131

15. (e) Glucose-6-phosphate deh)'drogenasc deficiency is an X·lillked disorder thar affects about 10% of AfricanAmertcan males. lbe lack of this ellzyme subjects henlOglobin to damage by oxidan15. illChxling drugs sucIJ as primaquine. sulfonamides.. nilrofuramoin, phenacetin. aOO aspirin (in large doses). lnfeaion can also cause oxidal..ive damage to hemoglohm. Heinz bodies damage lhe red blood cell membrane, givmg rise 10 intmvascular hemolysis. 1ñe "bite cells" result from overeager splenic macroplmges attempting to pluck OUI the Heinz bodies, adding an element of extravascular hemolysis. Heleroz)'gotes wilh a-lhalassemia llave no major problems. hut in cases of a-thalassemia major. perinatal dealh is the rule. Ukewise• .f3-thalassemia minor and sickle cell tmil are condilions with no major problems ¡md no relarion to drug usage. Some autoimmune hemolytic anemias can be drug relmed, but the hemol)'sis is predominanlly exlravascular.

8P6 350 P8D6 610-611 16. (e) llle i¡lCrease<! ferritin concentmtion aOO reduced total iron-binding capacilY are lypical for anemia of chronic disease. Increased levels of cylokines such as inlerleukin-I and tumor necrosis factor promote sequestralion of slorage iron wilh poor utilizéllton for erythropoiesis. Secretion of erythropoietin by lhe kidney is impaired. A variet)' of underlying diseases, inclooing cancer. collagen vascular diseases. aOO chrollic infections. roa)' produce Ibis pattem of anemia. !ron deficiency should produce a microcytic anemia with a lo\\' serum ferrilin. "'he patienl is unlikel)' lO llave aplastic anemia., because the platelet COUIll and WBC COUIll are normal. Microangiopathic hemolytic anemias are caused by serious acule condittons such as DIC; lhese palients have thrombocylopenia caused b)' widespread (hrombosis_ Megaloblastic anemias are macrocytic aOO do nol cause a large increase in iroll stores.

8P6 354

PBD6 630

17. (D) Throughout human history. malaria has been lhe driving force in increasing Ihe gene frequene)' for hemeglobin S. Individuals helerozygous fOl" hemoglobin S have Ihe sickle cell trail. llley are resistalll to malaria because lheir red blood cells sickle when parasitized aOO Iherefore are removed t'rom lhe circulalion by Ihe spleen. Thus, Ihe malaria\ parasite calmot complele i15 life c)'c1e. C. neoforIOOns can cause granulomatous disease in immunocompTOmised pttSOns. B. burgdoiferi is lhe spirochete lhat causes Lyme distase. T. po.llidum is lhe infecttous agenl causing syphilis. C. peifri"gens ma)' produce gas gangrene following soft tissue injuries.

8P6345 P8D6 389-390. 611

18. (A) The paoc),topenia and absence of a reticulocytosis strongly suggest bone manow failuTe. Aplastic anemia has no apparenl cause in one half of cases. In other cases, drugs aOO IOxins ma)' be identified. Drugs such as chemolhernpeulic agents are best known for Ihis effecl. A preceding vir.tI infection may be identified in sorne cases bUl bacterial infections do not cause aplll.'ltic anemias. Persons wilh panc)'topenia are subjecl to bleeding disorders from Ihe low platelet I.:OUIll and lo infectiOllS from lhe low WBC count. Dielllry hislory would not be helpful beeause Ihis c1inical and labomlory picture is not chllraclerislic of iron


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DISEASES OF ORGAN SYSTEMS

defidency or vilamin 8 12 deficiency. Menstrual hislOry would be relevanl if she had hypochromic microcYlic anemia. The only known familial cause of aplastic anemia O·e., Fanconi's anemia) is mre. BP6357 PBD6630-631 19. (A) This paliem ha<; so--called aUlosplenectomy Ihat results from Ihe multiple infarctions Ihal occur a<; a consequence of lhe sickling phenomenon. In childhood. Ihe spleen may inilially be enlarged from engorgemelll of splenic sinusoids wilh Ihe abnormal masses of sickled cells, bul hypoxic lis~ue damage ensues. Terrllinally, this patiem developed a va<;o-occlusive crisis affecting the lung. f3thalassemia major can lead lO splenomegaly from eXlrame<!ullary hem310poiesis. Some of Ihe largesl spleens occur becau~e of malaria. \Vilh ITP, the spleen is usually of normal size. In aUloimmune hemolytic anemias, fhe spleen may increase in size from exlravascular hemolysis and/or extramedullary hemalopoiesis. BP6 346 PBD6 614

20. (E) The severilY of hemophilia A depends on Ihe amoum of faclOr VO] activily. Wilh less than 1%, there is ~evere disease, aOO joinl hemoIThages are common, le¿lding to severe joilll deformity with ankylosis. Mild (1% lO 5%) and modernle (5% to 75%) aClivity is ot1en asymplomatic. excepl wilh severe trauma. The bleeding lendency is nO! associaled with splenomegaly. Pelechiae, seen with thrombocylopenia, are nOI a fealure of hemophilia Factor VIlI deficiency does not affect Ihe lifespan of RBCs. Bccause persons wilh factor VO] deficiency are not dependelll on RBe trnnsfu<;ions, iron overload is not a usual consequence. BP6 389 PBD6 638 21. (O) The presence of thrombocylopenia. increased PT and PlT values, fibrin split producIs, and lile low fibrinogen concentmtion suggest DIC, which was mosl likely caused by a retained dead fetus, an obsletric complication Ihal can lead [O DlC through relea"e of thrombopla"tins from [he felUs. This causes widespread microva"Cular Ihrombosis and consumes c10tting faclors and plalelets. Therc is no damage [O Ihe vascular endOlhelium or vascular wall. Platelel produc[ion is normal, but pJalelets are consume<! by widespread Ihrombosis of small vessels. There is no defecl in platele[ function. BP6385-3B6 PB 640-642

22. (E) llle baby mOSI likely has erythroblaslosis felalis because of malernal antibody coating the fetal cells. A fetal-maternal hemorrhage in ulero or a[ the lime of delivery in a previous pregnancy (or wilh previous tmnsfusion of incompatible blood) can sensitize Ihe molher so thaf IgG anlibodies are made. In subsequenl pregmmcies. Ihese amibodies (unlike Ihe natumlly occurring IgM anlibodies) can cross Ihe placenta lO altach to fetal cells. leading lO hemolysis. MOSl cases used to be caused by Rh incompalibililY (e.g., Rh-negative molher. Rh-posilive baby), but the use of RhoGAM adminiSlered at birth lO Rh-negalive mothers has e1iminated almosl all of such cases. However, other less common blood group anligens can be involved in Ihis process. BP6206 PBDó 473-474

23. (G) He has glucose-6-phosphate dehydrogenase deficiency. A drug thal leads to oxidative injury lO lhe RBCs, such as primaquine. can induce hemolysis. Oxidanl injury lO hemoglobin produces inclusion of denatured hemoglobin within RBCs. The inclusions damage the cell membrane direclly. giving rise to intmvascular llemolysis. Tllese cells have reduced membrane defonnabilily, and they are also removed from the circulalion by Ihe spleen. BP6350 PBD661O-611 24. (e) This paliem is a chronic alcoholic who has folale deficiency, giving rise lO megalobla~lic anemia. Folic acid and vi[amin B ll act as coenzymes in lhe DNA synlhelic palhway. A deficiency of eilher impairs Ihe nomlal process of nuclear matumtion. The nuclei remain large 311d primilive looking, giving rise lO megaloblasts. The malure red cells are a\so larger than normal (Le.• macrocYles). The nuclear maturation defecl affecls all mpidly dividing cells in the body. including other hemalopoietic lineages. Patients can have Ihrombocylopenia and leukopenia. Neulrophils often show defective segmentation, manifested by extm nuclear lobes. Polychromalophilic red cel1s represenl reticulocyles. and lhey are reduced in number because of the failure of marro...... lO produce adequa[e numbers of RBCs despile anemia. BP6356 PBDó 622-623 25. (E) The cresccnt-shaped RBCs (sickled RBCs) are characlerislic for llemoglobill SS. 1l1is disea<;e is most common in persons of African and easlem Arabian deseen!. The sickled red cells are susceptible lO hemolysis. bul lhey also can cause microvascular occlusions 3nywhere in the body, including abdominal viscera. These vaso--occ1usive episodes cause lissue ischemia and dealh. resulling in severe pain (i.e.• painful crises). a-Ihalassemia minor is asymploma[ic. and o-Ihalassemia major leads lO perinalal death. Paroxysmal noclumal hemoglobinuria is associaled with intravascular hemolysis. Hemoglobin C disease leads lO Ihe appeanmce of largel ceJls. BP6345 PBD6612-614 26. (O) In palients wilh here<!itary spherocytosis, spheroidal cells are Impped and des[royed in lile spleen because lhe abnorrllal red cells have reduced deformabiJily. Spleneclomy is beneficial because Ihe spherocytes are no longer delained by lhe spleen. Splenectomy ha" no effecl on Ihe synlhesis of speclrin; Ihe red cells in spherocytosis are not killed by opsonization. In ......arm antibody hemolylic anemias, opsonized red cells are removed by Ihe spJeen. BP6343-344 PBDó 607-609 27. (O) Tlle high MCV is indica[ive of a marked macrocylosis, greater Ihan would be .accounted for by a reticulo-cYlosis alone. The IwO beSI known causes for such an 3llemia. also known as megalobla"lic anemia when charac[erislic nlegaloblastic precursors are seen in lhe bone marrow, are vilamin 8 12 and fola[e deficiency. Because vilamin B ll is absorbed in Ihe [emIÍnal i1eum. its removal can cause B 1l deficiency. Chrollic blood loss and iron deficiency produce a microcylic pallern of anemia, as does iron deficiency. Hemolytic 3llemia is ulllikely several


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Cooptar 13

weeks after bJood tmn.~fusion. Anemi" 01' chronic disease is genemllya nomlOCytic anemia.

BP6356 PBDó 622-623 28. (C) He has DIe. which can result froro gram--negalive sepcicemia. This is a fom1 of microangiopalhic hemoIytic anemia in which there is deposition of fibrin strands in small vessels. 1ñe RBCs are damaged during passage belween lhese stmnds. Coagulation factors and platelets are consumed. something which does not occur with othe1" fonns 01' hemolylic anemia. Paroxysmal nOClurnal hemog10binuria and the hemolylic anemias do not Iypically cause a consumptive coagulopalhy. Thalassemias produce chronic anemia wilh ineffective erythropoiesis. and there is also an extr.lVa5Cular hemolytic componelll without a bleeding complication. Aplastic anemia refers lo Ihe loss 01' marrow stem cell aclivity and is Iherel'ore associaled wilh anemia. leukopenia, and thrombocytopenia. It can follow infections, moslly viral bul rarely bacterial.

BP6343 PBD664O-642 29. (A) The cumulative damage lO Ihe spleen in sickle cell anemia results in aUlospleneclomy, leaving behind a small fibrotic remnant of this organ. 1ñe impaired splenic fuoction wilh inability to c1ear bacleria from the bloodstream can occur earJy in childhood. leading lo infection wilh encapsulated bacterial organisms. 1ñere is no impairmenl in produetion or funetion of netJtrophils. Levels 01' serom complement are normal. Ad~ioll belween eOOol.heLial cells aOO red cells is increased in sid:!e cell anemia

BP6346-347 PBD6 613-614 30.

(A) 1ñe acute blood loss, in this cao;e probably intraperiloneal hemorrhage, results in a reticulocytosis froro marrow stimulalion by anemia. Leukoerythroblaslosis is Iypical for a myelophlhisic process in the marrow. Basophilic stippling of RBes suggesls a marrow injury, such as wilh a dn'g or toxin. Hypocllromic red cells occur iJl iron deficiency and Ihalassemias. both associaloo with reduced hemoglobin synthesis. AcUle blood loss does nol give rise lo iron deficiency. Schistocyles suggest a microangiopathic hemol)1ic anemia thal may accomp:llly shock or sepsis.

BP6342 PBDó 605-606 3l.

(A) The MCV, measured in the obscure unit of femtoliters (0..). provides an indicalion of lhe average size 01' RBCs. The MCV is a directly measured value. 1ñe MCH value indicares how muctl hemoglobin is in eac:h cell, and the MCHC iOOicates how mucll hemoglobin is present in a given volume of packed RBCs. 1ñe red cell distrihulion width provides a measure for variation in size of the RBCs aOO is highest with hemolylic anemias. 1lle hematocrit is calculated by automaled inslruments from multiplying lhe RBC counl by Ihe MCV; the simple "spun hematocrit" jusi provides the packed cell volume as a percelll of lhe 10tal volume 01' lhe 5alllple of blood.

BP6 342

PBDó 605

32. (C) TItis palienl ha<; paroxysmal noclumal hemoglobinuria. This disorder results from an acquired myeloid

REO CEllS ANO BlEEOING DISORDERS

133

slem cell membmne defect from a mutation in lhe PIGA gene. A mutation in this gene prevents lhe membrane expression 01' certain proteins Ihat rcquire a glycolipid anchor. 1llese include proteins lhal prolecl cells from Iysis by spontaneously aclivated complemenl. As a result, RBCs, granulocYles, aOO plateJets are exquisilely sensitive lO lhe Iytic activity 01' complemenL 1be red cell Iysis is intravascular aOO hence palients can have hemoglobinuria (i.e., dark urine). Defects in platelet Function are believed lO be responsible for venous thrombosis. Recurrent infections are pos.'libly cause<! by impaired leukocyte functions. Patients with paroxysmal nocturnal hemoglobinuria mal' also have acute leukemia or aplaslK: anemia as complications. TI1e glucose-6-phosphale dehydrogenase deficieney has an episodic course from exposure lo agenls such as drugs Ihat induce hemolysis. Spectrin mut,ltions give rise to heredital)' spherocYlosis. Mutalions in J3-globin chain can give rise to hemoglobinopathies such as sickle cell anemia. Faclor V mutóltioll can presenl wilh Ihromboses, bul there is no anemia or leukopenia.

BP6351

PBDó 619-620

33.

(D) The reduced J3-globin synlhesis results in a relative excess 01' a-g1obin chains that precipitate in RaCs and their precursors. 1ñese precipilales make the cells lllOr"C susceptible lo damage aOO removal. This intrnmedullary loss 01' mi cell precursors is referred to as ineffective erythropoiesis. UlÚortunately, il aetS as a trilllle1" for grealer dietary absorption of iron by unknown mechanistnS. HemoIysis of red cells in lhe periphery (e.g., spleen. live1") releases iron that can be reused for hemoglobin synlbesis. In megaloblastic anemias. lhere is enough iron hut not enough vitamin B'2 or folate. In sickle cell anemia, the J3globin chains are abnormal, leading 10 sickling of red cells, which are then destroyed in lhe spleen. However. lhere is no Lneffective erylhropoiesis.

BP6347-348 PBDó 615-616 34. (8) llle patienes hislOJ)' is Iypical 01' hemophilia A caused by a fllctor Vl11 derect or deficiency. The affecled palienl is male and has mOlle rellltives who are affected (i.e., X·Jinked Irtlnsmission). There is hislory 01' bleeding, especially into joints. PTf is prolonged because faClor VIU is re<luired for Ihe intrinsic pathway. PT is normal because lhe eXlrinsic pathway <loes nol depend on the function ol' factor VIII. TIte inability lO correcl P"IT by mixing wilh normal plasma is importanl. 11' Ihe p3lienl had a deficieney OI1ly 01' factor VIll, the addition 01' no..ma! plasma, a soura: 01' factor VIll, would llave correcled the PTT. Failure lO correct P"IT by normal plasma iOOicates lhe presence 01' an inhibilor of factor VIII in the patienl's serum. Such inhibilors are presenl in about 15% of the patients with hernophilia.

BP6 3B9 PBD6 639 35. (A) 1be hislory in Ihis ca~ is similar to Iha!: in question 34. However, lbe PTf is correcled by normal pooled plasma. TIte patient has hemophilia A cause<! by faclor VUI deficiency, aOO inhibilors 01' factor vm are abselll from palienl's serum. An in vitro mixing l>1Udy 01' palienl and pooled pla<;ma such as this usually correCls an abnormalily caused by a deficiency 01' a procoagulant fac-


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OISEASES OF ORGAN S'r'STEMS

lor, bul if lhere is <In inhibilor of coagulmion in the patient's plasma. lhe c10lting les! will show un abnormal result

BP 3B9 PllD 639 36. (D) lbis paliem has gum bleeding aOO excessive nlCnSlrua! bleeding wilh a norma! plalelel COlIlU. von Willebrnnd disea.-.e is a Fairly common bleeding disorder, wilh an eslimated frequency oF 1%. In most cases. it is inheriled as an autosomal dominanl trail. In Ihese cases. a rcduction in lhe qualltity of von Willebralld factor impairs platelet adhesion lO danmged vessel walls. and hcmostasis is compromised. Because von Willebr..tnd factor acls ,l~ a calTier for faclor VIU, Ihe level of lhis procoi.lgulalll protein (needed for the intrinsic palhway) is diminished, as in this case. However, the le\'cls of factor VIlI are rarely reduced enollgh lO be c1inica!ly significant. Prolonged prf corrected by norma! plasma is a reflection of factOl" VIII dcficicncy.

BP6 388-3B9

PB0663B-639

37. ("1 Reduced pl3lelet number may resull from decreased prodUdion or increased deslruclion. Marrow examination in lhis ca'iC reveals p1enty of megakal')'OC}1eS, exc1uding decreased production. Acceleraled destruction is often immunologically mediated. It may resull from well· known autoimmune diseases such as SLE. or il may be idiopathic. Whcn al1 known causes of lhrombocytopenia are excluded, a diagnosis of ITP should be made. This patient seems to have no other symptoms or signs aOO has no history of drug inlake Or infections that can cause lhromOOcytopenia. ITP is mosl likely. Thrombotic TIV is another emity to be considered. This is lypically ~sociated wilh fever, microangiopalhic hemolytic anemia neurologic symptoms. and renal failure. BP6387 PB06634-636 38. (O) This patient. of Mediterrnnean origin, ha~ J3-thal· assemia major. In this condition, there is a scvcre reduclion in the s)'llthesis of J3-glubin chains wilhout impairment of fr-globin synthesis. '111e free, unpaircd fl'-globin chains 101111 aggregates thal precipili.lte within normoblasls and CllUse them lO undergo apoptasis. The dClllh of red cell precursors in lhe bone marrow i,<¡ called inerreclive erylhropoiesis. NOl only tIoes Ihis cause anemia, but il also increases lhe absorplion of diet.ary iron. giving rise 10 iron overload. TI1e SC\'ere anemia triggers erylhropoielin synthesiso which expands lhe erythropoietic marrow. lñe marrow expansion encroaches on lhe bones, causing maxillofacia! dcformilies. Extramedullary hemalopoiesis causes hepatosplenomegaly.

BP6347-348

PBD6615-617

39.

(O) Iron deficiency is lhe masl common torm of anemia worldwide. nlC lack or iron impairs heme synthesis. The marrow response is lO "downsize" lhe RBCs, resulting in a microcytic and hypochromic anemia. TImlassemias are uncommon excepl itl cel1ain geographic areas. Likewise, infections and melaslases that illvolvc marrow are not comO. mon overall, aOO anemia is probably the easiesl problem lo treal in a patient with such a problem. Toxic injuries. ofien fmm drugs. are uncommon.

BP6 342. 353

PB06 627 -62B

40. (E) TIle fmilin is a measure of storage iron, because il is deri\'ed from !he tOla! body storage pool in Iiver, spleen. aOO marrow. Aboul 80% of funclional body iron is cootained in hemoglobin; the remainder is :n muscle m)'Qglobin. Transfcrrin is a serum trnnsport protein for ¡ron ane:! it is usuall)' about 33% saturated wilh iron. Persons with se\'ere liver disea<;e may have an elevaled serum fcrritin level becatL<;e of release from liver stores. 1ñe serum iron concentration by itself gives no indic..lion of iron stores, because in anemia of chronic discase, the iron leve! may be norlllal lO low, but iron stores are increased. The hemoglobin can be arfecled by Illore Ihan jusi iron slores. A bone marrow biopsy gives a good indicalion of iron SIOres. because the iron stain of lhe marrow demonstrales hemo,<¡iderill in m<lCrophages, but such a biopsy is an expensive procedure.

BP6 353

PBD6 627 - 628

41. rO) Patienls with sickle cell anemia have painful 01ses lhat represenl episodes of hypoxic injury aOO infarction caused by microvascular ocdusions. Bones of hands and fcet are frequently affecled. 1be \'aso-occlusion results from increased adhesiveness 01' damaged red cell membranes lo vascular endolhelium. lñe altemative complement pathway may have defects in sickle cell anemia tb¡ll impair opsonization of encapsulaled b¡¡cleria alld hence increase susceptibility 10 infection. The exlent of red cell sickling is correl¡¡ted wilh the degree ol" anemia. bul il is not correlated with Vaso-ocduliive episodes.

PBD6 614-615 42. (B) Tear-<lrop RBCs are indicalive of a myelophthisic disorder (j.e., somelhing filling the bolle marrow such a<> fibrou... COfinedive tissue). lñe leukoerythroblastoois, inc1udin~ immalure RBCs a1ld \VBCs. is mos:l indical.ive of m),elofibrosis. Splenomega!y is also typically seen in myelofibrosis. A leukoerythroblastic picture may a!so be seen with infections aOO metaslases involving the marrow. Marrow packed with myeloblasts is Iypical of acute myeloid leukemia. In Ihis condition, lhe peripheml blood would 31so show myeloblasl.S and failure 01' myeloid Illaturation. Reo. placemenl of marrow by fat QCcurs in aplaslic anemi,l, which is charnclerized by pancylopenia. Mega!oblasls in the marrow would indicate rolate or B I2 deliciency-bolh causing macrocytic anemia. Hyperpla<>ia of normoblasts occurs in hemolylic anemias. L..eukoel)'throblastosis is nol seen in hemolylic anemias.

BP6357

PB06632-633

43. (E) Althougtl both folate and B l1 deficiency give rise lo a macfOC}1ic anemia. a deflCiency of vilamin B'2 can also resull in demyelinalion of lhe poslerior and laleml columns of the spinal cord. The anemia caused by B I2 dcficiellcy can be ameliorated by increased administf'"<lIion of folale. masking the pOlelllial neurologic inju!)' by improving lhe anemia. Treating Sl2 deficiency does not improve the anemia caused by folate deficiency. Folale has no cofactor for absorpliOll, but B'2 Illust be colllplexed to inlrinsic faclor. secreted by ga..tric pariclal cells. and Ihen lhe complex must be absorbed in lhe lerminal ileum, so diseases such as atrophic gastritis and Crotm disease may affeec 8 12 absorption more than tOlale. 11Je periphcral


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smear may appear the same, and offers no means for distinguishing these defidendes. An aplastic anemia is unlíkely lO re..<;ull from a nulrilional deflciency. BP6 356 PBD6 625 44. (e) llle hemolysis Ihat accompanies sickle cell ane~ mia results in an increa<;e<! indirect hyperbilirubinernia Ihm favors lhe development of gaJlstones wilh bilirubín pigment. Cintlosis Olay occur because of hemochromatosis in Jj-thalassemia major. C..hronic atrophic gastritis lead<; to loss of parietal cells and lhe resulting vitamin 8 12 malabsorrlion causes pemicious anemia. Slillbirths suggest thalasseOlia major. Esophageal webs occur very uncornmonly in the seuing of chronic iron deficiency anemia. BP6347 PBD6 613-614, B93-894 45. (8) He has OIC fmm gram-negative septicemia. Multiple organs are at"fected, because Ihe microlhrombi lead 10 lissue ischemia and necrosis. Aclivalion of plasmin occurs, leading to fibrinolysis alld generalion of fibrin split produclS. DIC is a consumplive coagulopathy ill which the PT and the P1T are increased and platelets are reduced (although their function remains normal). A bleeding time should nol be ordered if Ihe platelel count is less Ihan IOO,roo/MI-. bea.lUse il will always be abnormal. The fi~ brinogen increases in a variety of inflammatory or infectious condilions, but in a consumptive coagulop<\thy such as OIC, lhe fibrinogen concentralion should be low. Thromboeytosis may lead lo Ihrombosis. hemorrhage, or both. because the plalelels are oflen abnonnal and increased in number, bUI microthrombi are not typical for this condilion. BP6384-386 PBDó 640-642 46. (A) [n Jj-thalassemia major. Ihere is a significant component of ineffeclive erythro¡x.>iesis, leading lo expansion of lhe marrow and a slimulus to aboorb more iron from the diet. The excess iron builds up in the tissues, resulting in hemoc:hromatosis with infiltmlive cardiomyopaIhy, hepatic cirrhosis, and "bronze diabeles" from pancrealic islet dysrunclion. In comparison, the hemolytic anemia is Olild in Jj-thalassemia minor, and there is vel)' lillle ineffective el)'thropoiesis. Hemoc:hromatosis is particularly detrimental to the Iiver and healt. Chronic anemia may require RBC transfusions that acld even more iron lO body stores. Other hemoglobinopalhies do nol have as significant a coOlponent of ineffective erythropoiesis, allhough any condilion Ihat lead<; lo Iransfusion dependellCY Olay be complicaled by heOlochromatosis. BP6349 PBD6616-617 47. (B) Such painful erises in llll allemic patienl are indicalive of sickle cell crises wilh homozygous hemoglobin S. During the crises, the sickle<! cells form microva.<:cular

RED CEllS ANO BLEEOING DISORDERS

135

oc:c!usions lhat produce lissue hypoxia. Tear-drop cells are indicative of myelofibrosis. Schistocytes, or fragmellted red cells, are seen in microangiopalhic hemolytic anemias, as may occur in Ole. Microcylosis can be seen with iron deticiency or wilh Ihalassemias. Spherocytosis can occur with hereditary spherocytosis or wilh hemolytic alleOlia~. BP6347 PBD6613-614 48. (E) Haploglobin is a serum protein that binds lo free hemoglobin. OnlinariJy, circulatillg hemoglobin is contained wilhin RBCs, bUI hemolysis can release free hemoglobin. The haptoglobin is use<! up as the amount of free hemoglobin illCrea"es. SLE is an autoimmune disease thal can result in hemolysis by means of autoantibodies directed at RBCs, and lhe direcl CooOlbs tesl resuh is oftcn positive. An elevale<! d-Dimer level suggesls a microangiopathic hemolytic anemia. Decrea<;e<! iron may cause a hypochromic, microc:ylic anemia, bul with hemolysis, lhe RBCs get recycled, and the iron is not losl. AII e1evaled anlinuclear antibody liter may indicate SLE or olher autoimmune disease, bul il does nol predicl hemolysis. BP6 343, 351 PBD6 606 49. (G) The iron concentration and iron~bindillg capadty are bolh low. However, unlike in anemia of iron deficiency, serum ferritin level is increased. This is typical of anemía of chronic disease. Underlying chronic inftammaIOry or neoplastic diseases increase lhe secrelion of cytokines such as interleukill-I, lumor necrosis factor, and inlerferon~")I. These cytokines depress erylhro¡x.>iesis. BP6 354 PBD6 630 50. (J) The diagnosis of Tfp is base<! on finding tr.\ll~ sient neurologic problems, rever, IhroOlbocytopenia, l11i~ croangiopathic hemolytic anemia, and acule renal faílure. These abnormalities are produced by small platelel-fibrin Ihrombi in small vessels in multiple organs. Heart, brain. and kidney are oflen severely affecled. BP6 387 -388 PBD6636-637 51. (A) The marked reliculoc:ytosis and Illarrow hype'l'la+ sia indicale thal the marrow is responding lo a decrease in Racs. The reticulocytes are larger RBCs tha! slíghtly int....ea.<;e the MCV. lron deficiency impairs Lhe ability of lhe OlaITQw lO moum a significant and suslained reliculocytosiso lron deficiency anemia is typically microcylic and hypochroOlic. Lnfiltrative disorders such as metastases in marrow would iOlpair Ihe ability 10 mounl a reticuloc:ytosis of this degree. The normal Coombs test results exclude an autoimmune heOlolytic anemia. An apla<;lic marrow is vel)' hypocellular and unable lO respond lo anemia. It is associa1ed with pancytopenia. BP6 342-343 PBD6606-1»7


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CHAPTER

14 White Cells, Lymph Nades, Spleen, and Thymus BP6 Chapter 12 - The Hematopoietic and lymphoid Systems PBD6 Chapter 15 - Whfte Cells. lymph Nades. Spleen, and Thymus

l. A 15-year-old male prcsellls wilh high fever of 10 days' duralion. Physical examinalion reveals scatlered pete+ chia! hemorrhages. There is no enlargement of liver 01' spleen 01' Iymph nodes. Bone marrow examination does not show any abnormal cells. The complete blood count (CBC) demonstrntes a hemoglobi n concentmtion of 13.2 gldL. he+ mmocril of 38.9%, mean ceU volume (MCV) of 93 n., plalelel oounl of 175.000ljlL, and white blood cell (WBC) oounl of 18501ML, with the differential count showing 1 segmel1led neulrophil, 98 Iymphocytes. and 1 monocyte per lOO WBCs. These findings are most Iikely caused by

O (A) AcUle Iymphocytic

(01'

Iymphoblastic) lellkemia

(ALL)

O (B) Acute myeloid lellkemia O (C) Aplastic anemia O (O) Idiopathic IhrombocYlopenic purpur<l O (E) Overwhelmillg bacterial infcction 2. A 9-year-old boy presents with a genemlized seborrheic skin eruption and fever. He ha" been diagnosed and lrealed for olilis media severa! times in Ihe pasl year, He also has lI1ild Iymphadenopathy along with hepalomegaly, and splcnomegaly. The e1ectron micrograph shown in lhe figure \Vas taken frOIll a mass lesion involving lhe masloid bone. The most likely diagnosis is

O O O O O

(A) (B) (C) (O) (E)

136

Acute Iymphoblastic leukemia (ALL) Multiple myeloma Hodgkin disease, mixed ccllulalllY Iype umgerhans cell hisliocytosis Oisseminaled tuberculosis

CourtCliY of Dr. George Murp/ly, Uoi\'crsit)' of Peoos)'l\'anill &11001 of Medicine, I'hiladclphill.

3. A 67-year-old male has experienced weakness, fatigue, and weight loss worsening over a period of seveml months. He now has decrea'iing vision in bolh eyes, along with headaches ¡Uld dizziness. His hands are scnsilive lo cold. On physical examinalioll, he has genernlized lymphadenop¡¡thy along \Vith hepalosplcnomegaly. Laboratory invesligations reveal hyperprotcinemia, wilh a serum prOlein level of 15.5 gldL and albulllin concentrallon of 3.2 gldL. A bone marrow biopsy sho\Vs infiltration wilh sll1all plasmacytoid Iymphoid cel1s wilh Russell bodies in the cytoplasm. Additional inve5úgarions are most likely lO reveal

O (A) A Illonoclonal IgM spike in lhe serum

O (B) Punchcd-oul Iytic lesions in lhe skull


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o

(C) Hypercalcemia

O (D) Bence Jones proteinuria O (E) 1(14;18) translocation

WHITE CEliS. LYMPH NOOES. SPLEEN. AND THYMUS

137

of 67.1%, MCV of 94 fL, platelet count of 453,000I¡..tL, aOO WBC counl of 78OO1,u.. His problems rnost likely slem from O (A) M)"elodysplaslic s)'OOrome

4. A 37·year-old femaJe presents with a fever of a week's duration. A CHC shows a hemoglobin oona=nlralion of 13.9 g/dL, hemalocrit of 42.0%. MCV of 89 fL, plate.lel count of 210.00(}'JLL, aOO \VBC COUnl of 56,00(}'JL1- The differential oount shows 63 segmented neutrophils. 15 baOO cells. 6 metanlyelocytes. 3 rnyelocytes. 1 blasl, 8 lymphlT eytes, 2 monocytes, and 2 eosinophils per 100 WBCs. The peripheral blood leukocyte alkaline phosphatase score is increased. TIle mosl likely diagnosis is

O (A) Olronic myelogenous leukemia (CML) 0(8) Hairy cell leukemia O (C) Hodgk.in diseao;e, Iymphocyte depletion Iype O (D) Leukemoid reactiOll O (E) Acute Iyrnphoblaslic leukemia (ALL) 5. A 12-year-old hoy presenls wilh howel obslruction and abdominal distention. Abdominal compuled lomography (CI) reveals a 7-cm mass involving lhe region of lhe ileocec-.t1 valve. Hislologic examination of lhe resecte<! rnass shows sheets of imermediate-sized Iymphoid cells with nuclei having coarse chrornalin and several nocleoli. 1ñere are many miloses. A ·'starry sky" pauem of macrophages is seen. A bone marrow biopsy is negaLive for Ihis cell population. CYI~enetic analysis of lhe Iymphoid cells from the ma.~ reveals 1(8;14). The most probable diagnosis in Ihis case is O (A) Diffuse large 8-cell Iymphoma 0(8) Follicular Iymphoma O (C) Acule Iymptloblastic leukemia O (O) P1asmacyloma O (E) 8urkiu Iymphoma

6. A 53·year.md maJe presems wilh an enlarged supraclavicular Iymph node, and physical examinalion reveals enlal'gemenl of Ihe Waldeyer ring of oropllllryngeal Iymphoid tissue. Tllere is no hepatosplenomegaly. Lymph node biopsy reveals replacemenl by a monomorphous population of large Iymphoid cells with enlal'ged nuclei and prol11inenl nucleoli. The C8C is IlOrmal except for findings of mild anemia. ImmunohiSlochemical staining and Oow cytometry of the node reveals that ITlOSl 1),ll1phoid cells are CO 19~. OJJO~, C03, CDl5-. aOO lem'¡nal deoxynocleotidyl transfernse negative (fdT-). TlleSe c1inical, histologic. aOO phenot)'pic fiOOings are mest oonsistellt with a diagnosis of O (A) Chronic lymphadeniLis

0(8) O (C) O (O) O (E)

Diffuse large 8-cell Iymphoma Hodgkin disease Lymphoblastic I)'mphoma Small lymphocytic Iymphoma

7. A 5O-)'ear-old male presents wilh headache aOO di7.Ziness. He has a1so experienced generalized prurilUS of a severe nalure. He has had these problems. along with dark slools. for several momhs. His stool is posilive for occult blood. and blood pressure is 165190 111m Hg. A CBC shows :l hemoglobin concentmlion ol' 22.3 gldL, hematocrit

O (8) Essenlial Ihromboc)'tosis O (C) Chronic m)'elogenous leukemia (CML) O (D) Erythroleukemia O (E) PoI)"cythemia vera

8. A 5Q.-year-old male was diagnosed with a diffuse large cell Iymphoma of B censo He· underwenl inlensive chemotherapy. and a complete remission was achieved that lasted for 7 )'ears. He IloW presents wilh faligue aOO pulmonary and urinary tr.w:t infeclions. A CSC shows a hemoglobin concentmtion of 8.7 g/dL, hematocril of 25.2%. MCV of 88 lL, platelet ooum of 67.00ClI¡..tL, ¡lIld WBC ooum of 2,3001¡..tL, with a differenlial oounl of 15 segmente<! neulrophils. 5 band cells, 2 melarnyelocytes. 2 l1lyelocytes, 6 myeloblasls, 23 Iymphocyles, 35 monocytes. ,md 2 eosinophils per 100 WBCs. Abone marrow biopsy shows 90% cellularilY wilh l1lany iml1lalure cells. including ringed sideroblasls. megaloblast~, hypolobated megakaryocytes, aOO myeloblasts. Karyotypic analysis shows 5q delelions in many cells. His present ooo<lilion is best char.tCterized as

O (A) A relapse of his previous I)'mphoma 0(8) Transformation of lhe Iymphoma imo m)"eloid leukemia O (C) M)'elodysplasia related to lherapy of his earlier lumor O (D) A de novo acule myeloblastic leukemia O (E) M)"eloid metaplasia wilh m)'elofibrosis 9. A 63~)'ear-old female experiences a buming sensaLion in lhe hands aOO feet. and she has had an episode of <Jeep venous Ihrombosis in lhe past 2 monlhs. 011 physical examinalion, the spleen aOO liver appear lO be enlarged. The periphernl blood smear shows abnormally large pl3lelets. The oomplete blood ooul1l shows a hemoglobin oollcentmtion of 13.3 gldL, hem3locrit ol' 40.1%, MCV of 91 fL, platelet counl of 657,00ClI¡..tL, and WBC of counl 17,400/ M-L. The mosl likely diagnosis is O (A) Essential Ihromboc)'lhemia O (B) Chronic m)'elogenous leukemia (CML)

O (C) M)'elofibrosis wilh Ill)'eloid melaplasia O (O) Acute myelogenous leukemia O (E) PoI)'C)1hemia vera For each of lhe c1inical hislOries in queslions 10 aOO 11. match !he most c10sely .associated palhologic finding: (A) (8) (C) (O) (E) (F) (G) (H) (1) (J) (K) (L)

Decreased visual acuity Disseminated inlravascular coagulopathy (01C) Generalized exfoliati\re el)1hroderma l..eukostasis Mandibular rnass Mediaslinal m.ass Renal am)'loidosis Scrofula Sebontleic skin elUptions Sinus histiocytosis Small intestinal obstruction Splenomegal)'


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Part 2

DISEASES OF ORGAN SYSTEMS

10. A 9-year-old boy living in Uganda has a O-cell Iymphoma Iha! on chromosome analysis reveals a 46,XY.t(8; 14) karyolype. Histologically. Ihe lumor is formed of intermediaLc~sized Iymphocytes with a high milolic rale. ( ) 11. There is .-ight axillary Iymphadenopalhy in a 39-year~ old female who ha.. a mammogram Ihal demonstrates a 2~ cm irregular righl upper ollter quadrant mass in her right breas!. ( )

O (O) Trans-relinoic acid O (E) Erythropoietin For each of the c1inical histories in qUestiOllS 14 through 16, match Lhe most dosely associated neoplasm: (A) AcUle Iymphobla..tic leukemia (a) Acule myeloblaslic leukemia (C) Chronic Iymphocylic leukemia (O) Diffuse large O~cell Iymphorna (E) Folliclllar Iymphoma (f) Hairy cell leukemia (G) Hoogkin disease, mixed cellularily Iype (H) MALT Iymphoma (1) Malllle cell Iyrnphoma (1) Mulliple myeloma (K) Mycosis fungoides (L) Thymoma CM) Waldenslrom macroglobulinemia 14. A 53-year-old female has had nausea with vOlmllllg and early satielY for several mOllths. AIl upper endoscopy reveals loss of Lhe rugal folds of the slomach over a 4 X 8 cm area of Ihe fundus. Gaslric biopsies reveal the presence of Helicobacter pylori organisms in Ihe mucus overlyillg superficial epitl1elial cel1s. 1l1ere are mucosal and submu(.'Osal monomorphollS infiltrales of smal1 lymphocytes. When she is Iremed for Ule H. p)'lori infectioll, her condilion improves. t )

12. A 61-year-old male gives a hislOry of back pain for several monlhs. A skull radiograph is shown here. He has no Iymphadenopathy or splenomegaly. His serum blood urea Ilitrogell level and creatinine concentralion are found lO be sLeadily rising. He recelltly developed a cough prodllctive of yellowish sputum. and a sputum culLure grew StreptOcoccu.~ Imeumolliae. Dllring the collrse of his hospilalizalion, a bolle marrow biopsy is performed. The biopsy is mosl likely Lo show

O (A) Scaltered small granlllomas O (O) Numerous plasma cells O (C) Nodules 01' small malure lymphocytes O (O) Occasiollal Reed-Stemberg cells O (E) HypercellularilY wiLh many blasts 13. A 26-year-old male has elllarged, llontellder cervical Iymph llooes. A biopsy of one of lhe Iymph nooes reveals scatlered Reed-Sternberg cells alollg wilh macrophages. Iymphocytes, neutrophils. eosinophils. and a few plasma cells. Which 01' the following faclors elaboraled by Lhe Reed-Slernberg cel\s has led lO the appearallce o.. Lhe eosinophils wilhin Ihis lesioll?

O (A)

Plalelet~derived

O (O) Cyc1in 01

O

(C) Illlerleukill-5

growlh factor (POGF)

15. A 39-year-old male is known lO have been infecled with the human immunooeficiency virus (HIV) for lhe past 8 years. [)espiLe antirelroviral therapy wi!h zidovudille, sta~ vudine, and Relrovir, his HIV~ I RNA level has recemly beell rising and now is 28,(X)() copie...;JmL. He is found on physical examinalion lo have stool positive for occu1t blood. Sigmoidoscopy reveals a 4-cm mucosal ma..¡s in Ihe upper reclum. ( ) 16. A 50-year-old female presents wilh fatigue and pallor. Laboratory investigatiollS reveal a hemoglobin cOllcenlralion of 9 gmJdL, hematocrit of 28%, and reticulocyte count of 0.1%. The MCV, mean corpuscular hemoglobin concenIration (MCHC), alld serum ferritin leve! are normal. A bone marrow aspirate shows normal cel1ularity. bul Ihe cells of lhe erythroid series, such as prononnoblasts, normoblasts, and laler slages, are greatly reduced. Olher elemems are normal in number and differellliation. ( ) 17. In which of the following cOlldilions thal cause polycythemia is the serum erythropoietin extremely low?

O (A) Dehydration

O (O) Renal cell carcinoma O (C) Polycylhemia vcra O (O) Cyanotic heart disease O (E) High-altitude living 18. A 41-year-old male has a rever, with a temperalure of 39.2°C. His cae shows a hemoglobin concentralion of 13.9 g/dL, hemalocril of 40.5%, MCV of 93 fL, WOC of count 13,7501p:L, aOO plalelet count of 210,000/p:L. The difTerenlial counl is 75 segmenLed neutrophils, 10 baOO


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Chapter 14

WHIlE CEllS, LYMPH NODES, SPLEEN, AND THYMUS

139

cells. 10 Iymphocyles. and 5 monocytes per lOO WOCS. A bone marrow biopsy shows hypercellularilY. with a marked increase in myeJoid precursors al al1 Slages of malUration and in band neulrophils. Which of lhe following conditions is most likely lo be associated wilh lhese c1inical and hematologic findings?

O O O O O

(A) AC\lle viral hepalitis (O) Glucocortiooid lherapy (C) Lung abscess (1) Vigorou.~ exercise (E) ACUle m)'eloid leukemia

19. A 37-year-old maJe known to have been infecled wilh HIV for !he past 10 yea~ is OOmiued wilh abdominal pain of 3 days' duralion. Physical examination reveals abdominal distentioo wilh a!)sent boy.-el sounds. An abdominal sean reveals a mass lesion involving lhe ileum. He is taken lo surgeT)', and an area of bowel obstnJction in lile ileum is removed. The specimen is examined in lhe surgical palhology departmenl. and lhere is a finn. while mass lhal is 10 cm long and 3 cm in greatesl deplh. It infiltrales Ihrough lhe wall of lhe ileum. Histologic studies reveal a mitoticaJly acti\'C popullllion of CDl9' Iymphoid cells wilh prominent nuclei and nucleoli. Molecular analysis is most Iikely to reveal which of Ihe following viral genomes m the Iymphoid cells?

cr

O (A) Ep!:;tein-Barr virus (EOV) O (O) Human immunodeficiency virus (HIV) O (q Human herpesvirus Iype 8 (HHV~8)

O

(O) Human T-cell leukemia/lymphoma virus type I

(HTLV-I) O (E) Cytomegalovirus (CMV) 20. A 70-year-old maJe presems wilh increasing faligue for the 1a.~1 6 momhs. Hemmologic workup reveals a COC with a hemoglobin concentnllion of 9.5 gldL, hemalocril of 28%, MCV of 9Ofl., plalelel COlllll of 120,0001~L. and WBC count of 42,000I~L The periphernl blood smear shows absolute lymphocYlosis wilh a monolonous populalion of small. TOlInd, Illllture-lookillg Iymphocyles. Flow cytomelry shows the cells to be CDI9', CD5~. and TdT-. Cylogenetic and molecular analysis of the cells in the blood is mosl Iikely to reveal

O (A) t(9;22) lending to bcr~abl rearrangelllellt O (O) Clonal reammgement of immunoglobulin (Ig) genes

O (q Clonal reamlllgement of T-cel1 receptor genes 0(0) t(8;14) leading lO c-m)'c overexpression

O (E) t(14:18) leading to bcJ-2 overexpression 21. A 69-year-old waman complains of back pain. A rndiograph reveals a panial callapse of TII, along with sevesal 0.5- to 1.5-cm lrtic lesions with a rounded "soap bubble" appearnnce in the lhorncic and lumbar vertebrae. A bone marrow biopsy is penonned. and a smear of the aspirnte is shown in lhe figure. 1ñe most likely laboralOJy finding in this palielll is a (an)

O (A) Monoclonal gammopathy in the serum O (B) 1(9;22) in the kar)'Ol.Ype of malTo", O (C) Elevated leukocyte alkaline pha<;phatase score

O (O) Decreased serum alkaline phosphatase level O (E) Plalelel counl of 750,OCXJ/ILL 22. A 33-year-old female has hOO a hislO/)' of generalized fatigue and nighl sweats for several momhs. Physical examinalion Jeveals righl cervical Iymphadenopalhy. Biopsy of Orle Iymph nade reveals thick bands of fibrous connec· t¡ve tissue wilh intervening Iymphocyles. plasma ceUs, eosillOphils. macrophages, aud occasional Reed-Stemberg cells.. An alxlominal sean and bone marrow biopsy show 00 abnormalities. The sllbtype and stage of her Hodgk.in disease is

cr

O (A) LymphocYle preoominllJlCe. stage I O (B) Mixed cellularily, slage 11 O (C) Lymphocyte deplelion. stage 111 O (D) Lymphocyte predominance, stage II

O

(E) Nodular sclerosis. stage 1

23. A 7-year-old boy has painful, swollen Iymph nades in his r¡ghl inguinal region Ihat have worsened over Ihe pust week. An inguinal Iymph nade biopsy is performed. Histologically. the nade has large germiJllll cenlers containing numerous mitolic figures. There are numerous neulrophils about the follicles and in the sinuses. The most likely cause for these histologic changes is

O (A) O (O) O (C) O (O)

Acule Iymphoblastie leukemia Sarcoidosis Folliclllar Iymphoma Cal scrnlch disease O (E) Acute Iymphadeniris

24. A 39-year-old male has subarnchnoid aud gaslrointestinal hemorrhage. The WBC count is 75.000J~l. and most of the WBCs seen on lhe peripheral blood smear are hypergranular promyelocytes wilh numerous Auer rods. Schistocyte.~ are seen on the periphernl blood smear as well. 1ñe serum D-dimer Ie\-el is elevated. Cytogenetic analysis of cells from bone marrow biopsy is most Iikely lo yield which of lhe following karyotypic abnormalilies? O (A) 1(8'21) O CB) 1(9'22) O (C) 1(14'18) O (O) 1(15;17) O (E) 1(8:14)


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D1SEASES OF ORGAN SYSTEMS

25. A 4-year-old child has appeared listless fOr about a week. He now complains of pain when he is picked up by hilO mother, aOO he demonslrales irrilability on touching his amls or legs. In lhe pasl couple of days, several largc ecchyrnoses have appeared on his rigllt thigh and left shoulder. A complete blood COllnl reveals a hemoglobin concentralion of 10.2 gldL, hematocrit of JO.5%, MCV of 96 rL, platelet coom of 45.000I¡.tL. and WBC count of 13.99OIJ,LL. Examinalion of lhe peripheral blood lOmear shows blasts. 1ñese blaslS lack peroxidase-positive granules bUl do contain periodic acid-Schiff (PAS)-positive aur-egales and stain positively for TdT. Aow cylomelry shows !he phenotype of blaslS lO be CDI9'. CD3 , aOO slg-. He is mesl likely lO have

O O O O O

(A) Chronic myelogenous leukemia (CML) (8) Idiopathic thrombocytopenic pUJPura (q Acute myelogenous leukemia (O) Chronic Iymphocytic Icukemia (E) Acute Iymphobla..tic leukemia (ALLl

26. Massive splenornegaly is a characterislic c1inical feature of all of the following diseases except

O (A) Chronic myelogenous leukemia (CML) O (B) Myelotibrosis w¡lh myeloid metaplasia O (q Gaucher disease O (D) Kala-azar O (E) Inleaious mOllOnucleosis 27. A 69-year-old male notices the presence of "Iumps" in his right neck that have been enlarging during the past year. Physical examinaLion reveals tirol. nontender poslerior cervical Iymph nodes ranging from I to 2 cm in diameler. lñe overlying skin is ¡nlact aOO not erylhematous. Olle of lbese cervical lymph nodes is biopsied. Which of lhe 1'01lowing hislologic fealures provides lhe best evidenre for lhe presence of malignanl Iymphoma in this nocle? O (A) Presence of Iymphoid cells positive fOI" kappa. but not lambda, liEhl chains O (B) AbsellCC 01' 11 follicular pattern O (C) ProliferiltiOIl of s01ull cllpillaries O (D) Presence of cells thm stain with O1onoclonal antibody to the CD30 antigen O (E) Absence I)f plasma cells 28. A 42-yeur-old mOlle presenlS with generalized 1ymphadenopalhy along wifh fever and weight I05s. llle spleen lip is palpable on physical examinlltion. His peripheral blood WBC 00l.l1ll is 24,5W¡lLL, wilh a differcnlial eOllnt of 10 segmellled neutrophils, 1 bando 86 lymphocytes. and 3 mooocytes per 100 WBCs. A cervical Iymph nooe biopsy reveals a nodular panero of neoplastic smal1 Iymphoid cells. Abone marrow biopsy reveals infiltralt".'> of similar small cells. Cytogelletic analysis reveals t(II;14) in the neopla..üc cells. lOe most likely dia~is is O O O O O

(A) (8) (C) (O) (E)

Manlle cell Iymphoma Follicular Iymphoma Acule Iymphoblaslic leukemia Burkiu Iymphoma Small Iymphocytie Iymphoma

29. A 45-year-old ma1e has fever. weight loss. and Iymphadenopathy. The adellopathy becomes very tender afier a six-pack of beer. A Iymph node biopsy reveals effacement of Ihe nodal archilcclure by a population of small Iymphocyles, plasma rells, e05inophils, and macrophages. Which of lhe following additional cell lypes. which stain posilively for COI5, is characterislic of this disease?

O (A) Reed-Stemberg cell O (8) lmmunoblasl O (e) Epithelioid ccll

O (O) Neulrophils O (E) Masl cell JO. A 23-year-old female ha... a positive antinuclear antibody lesl with a liter of 1:1024 and a "rim~ pattem. An anli-double-slrandcd ONA test is also positive. She ha.. a malar skin rash on physical examination. He!" complete blood COOllt dernonslrales a hemoglobin concentraLion of 12.1 gfdL, hemalocrif of 35.5%. MCV of 89 fL. WBC COOIll of 45OO1¡.tL. and platelet count of 1D9,OOOI¡,tL Which of the following tindings is mosl likely to be demonslraled by a WBC difTerential coonf?

O (A) Eosinophilia 0(8) ThrombocYlosis

O (C) MonocyfOSis O (O) Neutrophilia O (E) Basophilia

Normal serum SP

G

A

M

K

+

Patient serum SP

G

A

M K f.. •

+ SP. §ftUITI proIcin tltClropt..~is; G. A. M. M. and A are grn with !>JX'Cific $Iai~ rOl' tgG. IgA. IgM. kappa I¡¡;hl chain. llfId lambda light dWm. rtSp«ti-dy. (CouT1c:sy 01' Dr-. I)¡,"id Sacb, Oepal'tmml el Pa.lhol-Of!y. Brigham and Wonltll·51~lal. 8oMon. MA.)


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31. The finding 011 serum prolein e1eclrophoresis shown in Ihe previous figure from a 58-year-old male wilh renal failure is mosl characleristicaUy associated wilh which of Ihe following labormory findings?

O (A) TdT' circulating blasts

WHITE CElLS. LYMPH NODES. SPlfEN. AND THYMUS

O O O O

(A) (O) (C) (O) O (E)

141

Vertebral compressed fractures Chronic renal failure Oisseminaled imravascular coagulalion (01C) Small intestinal obstruclion Perforated duodenal ulcer

O (O) Bence Jones proteinuria O (C) Bone marrow karyotype with 1(8: 14) O (O) Reactive amyloidosis

O (E) Hematocrit of 62% 32. The bcr-ab/ fusion gene fram Ihe reciprocal tmnsloca~ tion 1(9;22)(q34;qll) resulls in increa..ed Iyrosine kinase activity. This is mosl characteristic for

O O O O O

(A) (O) (C) (O) (E)

Follicular Iymphoma Chronic myelogenolls leukemia (CML) Hodgkin disease, lymphocyte deplelion Iype Acute promyelocytic leukemia Multiple myeloma

33. A 64-year-old male presenls with inguinal, axil1ary, and cervical Iymphadenopalhy. The nodes are fion and nontender. A biopsy of a cervical nade shows a histologic pattern of nodular aggregales of smull cleaved Iymphoid cells aOO lurger cells with open nuclear chromatin, several nudeoli, and moderate amounls of cytoplasm. Abone marrow biopsy reveals Iymphoid aggregales of similar cells. Karyotyping of these Iymphoid cells reveals Ihe presence ofl(14;18). He is mostlikely lo have

O (A) Hodgkill disea"e, nOOlllar sclerosis Iype O (O) Acute Iymphadenilis O (C) FoUicular lymphoma O (O) Manlle ceU lymphoma

O (E) Toxoplasmosis

35. The gross appearance of Ihe spleen shown in Ihe figure, from a 27-year-old male with rever alld leukocytosis, is most Iypical for which of the following condilions?

O (A) Melastatic carcinoma O (O) Acule myelogenous leukemia O (C) Hodgkin disease

O (O) lnfeclive endocarditis O (E) Disseminaled hisloplasmosis For each of Ihe clinical hiSlories in questions 36 and 37. match lhe most c10sely associated infectious agenl: (A) A~pergillw;[lImigafl/.s (13) /JartOIle/la l1ense/ae

(C) Cylomegalovirus (O) Epstein-Barr virus (E) Escl1erichja coli

(F) Helicobllcter pylori

(G) Hepatitis C virus (H) Herpes simplex virus (1) Slrollgy/oit/es ~"1ercora/ü (J) Tox01J/asma gOtU/j¡

(K) Varicella zoster virus 36.

A week afler beginning therapy for Pneumoeystis cllrpneumonia with trimethoprim-sulfamethoxazole, a 29year-old female ha.. a CI3C that shows a hemoglobin concentralion of 7.4 g/dL, hematocril of 22.2%, MCV of 98 fL, platelel count of 47,OOO/J-tL. and WBC counl of 18701 J-tL, with a differential coum of 2 segmemed neulrophils, 2 band ceHs, 85 lymphocytes, 10 monocylcs, and 1 eosilKlphil per 100 WBCs, A ches! radiograph I wcck laler demonslrates multiple. 1- lo 3-cm nooules in aH lung fields. ( ) tIltl

Courtl'l<Y of Dr. Robcrt W. McKcnna. Departmcnt of P'dIhülogy, Uni\'crSily of Texas Soulhwe~lcrn Medical School. Dalla.~. TX.

34. A 35+year-old male has experienced malaise for lhe past 3 months. A cnc is perfooned and shows a hemoglobin concelltration of 10.8 gIdL, hemalocril of 33.0%, MCV of 90 fL, platelet counl of 96.000JJ-tL, and WI3C count of 89,6OOIJ-tL. The peripheral blood smear has the appearance shown here. 1l1e mosl likely complication of Ihis condilion

"

37. A 23-year-old male undergoing chemolherapy for acute lymphoblastic leukemia has developed a fever and abdominal pain in Ihe paSI week. He now has asevere


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DISEASES OF ORGAN SYSTEMS

cough. His enc shows a hemoglobin concentralion of 12.8 gldL, hematocrit of 39.0%, MCV of 90 11.., plmelel coum of 221,OOO/,uL, and wnc count uf 16,475/,uL, with differential counl of 51 segmenle<! neutrophils. 5 band cells. 18 lymphOl:yles, S monocyles. and 18 eosinophils per 100 wncs. ( ) 38. A 41-year-old male has had several bouts of pneumonia in the pasl year. He now complains of vague ab<lomi~ nal pain and a dragging sensalion. Physical examinalion reveals marked splenomegaly. A complete blood counl shows a hemoglobin concentralion of 8.2 gldL, hematocrit of 24.6%. MCV of YO 11.,. WBC count of 24oo/,uL. and platelel count of 63,OOOI,uL. On the peripheml blood smear are many small leukocyt~<; with reniform nudei and pale blue cytopJasm with threadlike eXlensions. !mmunohistochemieal staining shows thal they mark with C020. Which of the following laboralory lesl findings is masl charaeleristic of Ihis disease? O O O O O

Tartrate-resistant acid phasphatase in Jeukocytes (H) Presence of Auer roos in leukocyles (e) Presence of Ph 1 ehromosome (O) Presence of toxic granulalions in neutrophils (E) Monoclonal IgM in serum

(A)

RBC per lOO WBCs, Abone malTOw biopsy shows 100% cellularity with many large blasls thm are peroxidase negative and nonspecific eslerase positive. She is most JikeJy to have

O (A) Acute Iymphoblastic leukemia (ALL) O O O O

(B) Acute rnegakaryocytie leukemia (e) Acute promyelocylic leukemia

(O) Acute etythroleukemia (E) Acute monocylic leukemia

41. Which of the following eombinations of phenotypic-. kmyotypic-, and age-related markers predicts the besl prognosis in acule Iymphoblastic leukernia? O (A) Early pre-B (COI9+, COlO', TdP); hyperdiploidy: 8 years old O (O) T cell (CD3', C02', TdP); normal karyolype; 2 years old O (e) Pre+B (COI9·, COlO', TdT', C,u'); 1(9;22); 4 years old O (O) Early pre-B (COI9', COlO', TdT'); 1(9;22); 1 year old

O (E) Pre-B (COI9', COlO'. TdT'. CIL'): normal karyoIype; 15 years old 42. A 51-year-old male presents with a generalized exfoIialive erythroderma. A skin biopsy reveals Ihe presence of Iymphoid cells in the upper dennis and epidermis. These cells have cerebrifonn nuclei with marked infolding of nudear membranes. Similar cells are seen on his peripheral blood smear. Which eombinalion of the foUowing phenoIypie markers is expressed on Ihe abnormaJ Iymphocytes? O O O O O

39. The peripheral blood smear showll here is from a previously healthy 26-year-old male who has had a low· grade fever, malaise, pharyngitis, and Iymphadenopalhy for a couple of weeks. The most likely risk faelor for the disease shown here is O O O O O

(A) An inheriled disorder of globin chain synlhesis

(13) Tmnsfusion of packed red blood cells (RBCs) (e) C10se personal eonlael (kissing) with his date

(D) Sharing infected needJes fOr intravenous drug use (E) lngestion of raw 0yslers

40. A 38~year-old woman presents with bleeding gums. Physical examination reveals hepatosplenomegaly and genemlize<! lymphadenopathy. A complete blood count shows a hemoglobin L"Oncentration of 11.2 gldL, hematocrit of 33.9%, MeV of 89 11.., plale1et count of 95,000/,uL, and WBC count of 45001,uL. 111e WBC differential counl shows 25 segmenled neutrophils, 10 band cel1s, 2 melamyelocyles, 55 Iymphocytes, S monocyles, and I nucleated

(A) CO}·.., CD4", COS(E) CD3', CD'-, CD8' (e) CDI9', slg' (O) CD19'. CDS' (E) CD33', CDI3'

43. A 65-year-old male presents wilh a I-year hislory that includes faligue, a 5-kg weight loss, night sweats, and ab<lorninal discomfon. His C8C shows a hemoglobin con~ eentmtion of 10.1 gldL, hematocril of 30.5%, MCV of 89 n~, platelet counl of 94.000/,uL, alld WBC count of 14,750/,uL. The WBC differenlial eount shows 55 segmented neutrophils. 9 band ceUs, 20 Iymphocytes. 8 monocytes, 4 metamyelocytes, 3 myeJocytes. and I eosinophil, with 2 nuclealed RBCs per 100 WBCs. The peripheral blood smear also demonstrales tear-drop cells. Serum urie acid level is 12 mgldL He has marked splellomegaly on physieal examinalion, aJthough no Iymphadenopalhy. A bone marrow biopsy shows exlensive marrow fibrosis along with cluslers of atypical megakaryocytes. Which of Ihe following pathologic findings in his spleen is mast likely lO aceoulll for the enlargement? O (A) Reed-Sternberg cells mixed with many more Iymphocytes, plasma cells. eosinophils, and macrophages 0(8) Proliferation of all hematopoielic lineages, with prominence of megakaryocytes O (e) Chronic passive venous (.."Ongestion and fibrosis


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o (D)

Multiple caseating granulomas contammg macrO'phages wilh His10plasmo copsulOlwn O (E) Diffuse infiltration by metastatic adenocarciooma

44. A 60-year-old male presents wilh vague abdominal discomfort accompanied by sorne bloaling and diarrhea The stool is posilive for occull blood. An abdominal cr sean reveals a 5 x 12 cm mass im'oIving lhe wall of the distal ileum and OOjacent mesenlery. A laparotomy is performed, and the mass is reseded. Microscopically, the mass is compOSed of s/leels of large Iymphoid cells wilh large noclei, prominent nucleoli. and frequenl miloses. The neoplastic cells are CD19' and CD20" aOO ha\'C the bcl-6 gene rearrangement. Which of the following progllos[ic features is most applicable lO this case? O (A) Indolem disease wilh survival for 7 lo 9 years wilhout lrealmenl O (B) Aggressive disease Ihat can be cured by aggressive chell101herupy O (C) Aggressive disease thal does not respond 10 chemO'lherapy and Iransforms lO acule leukemia O (D) Indolenl disease thal can be cured by cl1emolherupy O (E) Indolelll disease thal often undergoes spontaneous remission 45, A 45·year.-()ld male experienl.:ed a gradual \\'eighl loss for months, alollg with weakness, anorexia, and easy faligabilily. On physical examinalion, there was marked splenornegaly. A complete blood oounl showed a hemoglobin ooncentrotion of 12.9 g/dL, hematocril of 38.1 %. MCV of 92 fL, platdet counl of 41O,()()(YJ.lL, aOO WBC oounl of 168.()()(YJ.lL The peripheral blood srnear is depicled in part A of lhe figure. Karyolypic analysis showed lhe Ph' chn:>mosome. He underwenl chemotherapy Ihal reduced Ihe spleen Si7.e and lhe 100al leukocyle count lO the normal range. He remained in remission for 3 years but then began lo develop fatigue and experienced a Io-kg weighl loss. Physical examinalion revealed pelechial hemorrhages. A complele CSC showed a hemoglobin concentralion of 10.5 g/dL, hematocril of 30%, WSC COUIll of 40.000/¡..¡L, and platelet COUllt of 6O,OOO/¡..¡L. A peripheral blood smear is depicted in par! B of Ihe figure. Karyolypic analysis showed 2 Phi chromosomes and aneuploidy. Flow Cylornelric analysis of the peripheral blood showed CDI9",

WHIlE CElLS, lYMPH NOOES, SPlEEN. AND THYMUS

143

CDIO~. slg . C03- eeUs. Which of lhe following sequence of events is sUPPOr!ed by Ihese findings? O (A) Thil' palient had chronic myeloid leukemia (CMLJ previously and has developed a second malignancy of B cells. O (S) This palient hOO CML and has developed a lherapy. associaled myelodysplastic syodrome. O (C) This patient had CML and acule Iymphoblastic leukemia (ALL) al Ihe original presenlation. The CML is cured, bUI has persisted O (O) 'Olis palienl hOO transformation of a pluripotent Slem cell. manifesled initially as CML Wilh additional mulalions. lhe leukemic stem eelIs have now emerged as a B-Iymphoblaslic leukemia. O (E) The first and second presentalions are completely unrelaled; palienlS' charts should be checked carefully lo delermine if lhe Iwo sets of dala perlaill lO differelll individuals.

46. A l4-year-old boy complains of a feeling of discomfOr! in his ches!. A chesl radiograph reveals c1ear lung fields, but there appears lO be widening of lhe mediastinumo A Ihordcic cr sean demonstrates a IQ-.cm mass involving the anterior mediastinum. A biopsy of lhe mass reveals Iymphoid ceIls with lobulated Iluclei showing delicate., finely Slippled nuclear chrornalin. There is seant cylO'plasm. Many mitoses are seen. The cells express Tóf, COI, CD2, and CD5 antígens. The mosl likely diagnosis is O (A) Lymphoblaslic Iymphoma O (B) Burkitt Iymphoma O (q Hodgkin disease. nodular sclerosing Iype O (O) Manlle cell Iymphoma O CE) FoUicular Iymphoma 47. A 60-year-old female presentS wilh headaches and dizziness. Physical examination reveals a sornewhal COl'lgested faee with a cyanOlic appearance. There is mild splenolllegaly bul no other abnormal finding. Her blood pressure is nonnal. The patient's hislory reveals thal she has beell laking treallllem for heartburn with anti-uleer medicatiolls. Laboratof)' illvesligllliolls reveal a hemoglobill cOllcelltrlllioll of 17.5 gmJdL, helllatocril of 65%. 'Ole MCV, MCHC, and sellJm ferritin levels are normal. Tolal WBC count is 30,OOCN'J.lL wilh a differenlial of polymor-

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Soulhwcstcm Mcdicill Sclluol, Dalllls, TX.


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DlSEASES OF ORGAN SYSTEMS

phofludear leukocytc.~ 85%. Iymphocytes 10%. and monoerles 5%. Platelcl counl is 4OO.000I1J.L and the blood smear sho"'S abnormally large platdets. Her serum erythropoiclin levcl is undeteetable. and the kar)'otype is normal. Which of Ihc folluwing is a chard<.1cristic of the natural history of this disease'!

o O O O O

(AJ Death from Imnsformation of Ihe disease ¡mo acute B~lymphnbla~tic leukcmia (O) Onset of marrow librosis wilh exlcnsive exlraffiCdullm)' henulIopoiesis in Ihe spll.'Cn (e) Spomaneous remissions and relapses wilhout any trcatmenl (O) Gradual inerease in monoclonal serum immull().. globulins (El Dc\'clopmcnl of a gas:lric Iymphoma

A 17-year-oId female has experienced malaise fOl' weeks. starting with a mild pharyngilis. Her sclerac are slightly ieteric. and shc is mildly ancmic. 1ñe peripheral blood smear dcmonstratcs atypieal Iymphocytcs. Which 01' lhe following laboratory Ic...'St findings is mosl likely in Ihis case? 48.

~"cra1

O O O O O

(A) (B) (C) (O) (E)

Ba"ophilia Eosinophilia Monocytosis MOllospol lest positivity 46.XX.t(9:22) karyotype

For cach of lhe c1inical hislori<:s in queslions 49 and 50. match lhe mosl c1Q>Cly associated morphologie finding:

upper respiratory and middle ear infcctions with S. ¡me,,mo"iae for lhe pa"l year. A skull radiograph reveals an expansile. 2-cm l)'tie lesiOll involving the right parietal bcme. ( ) 51. A 2H-year-old ma.le is admittcd wilh markcd hypotensioo and shock. A CBC shows a hemoglobin concenlralioll of 14.1 gldL, hcmatocril of 42.6%. MCV of 9311.... WBC l."Ounl of 12.15Q1IJ.L. and plalelcl eounl of 127.5OO1pL The periphcral blood SOlear demOIlSlralcs a differenlial COUIlI of 71 ~gmcl1led ncutrophils. R ballll cells. 14 lymphoc)'les. and 7 monocyles per 100 WBCs. The I1cutrophils show cytoplasmic toxic granulations and DOhle bodies. Which of lhe following condilions is he mosl likcly to have? O O O O O

(A) (B) (C) (O) (E)

Tuberculosis Acute myelogcnous leukemia Ououie myelogcnou... leukcmia Bacterial septicemia Infectiou.. mononuclcosis

52. A 15-year-old girl has a CBC Iha! dcmonslralcs a hemoglobin conccntration of 14.7 gldL hemalocril of 43.1%, MCV of 92 fL. plalelel count of 233.000Ip.L and WBC count of 975OJ¡tl.. wilh the differential l."Ounl showing 58 scgmenled ncutrophils. 4 b¡md cclls. 22 Iymphocyles, 4 rnonocytes. and 12 eosinophils per lOO wacs. TIlese (jndings are mosl Iikely to be associaled with which of lhe following condilions? O O O O O

(A) Bacterial seplicemia rB) Bronchial aslhma (C) Chronic myelQl!enou... leukcmia (CML) (D) Leukemoid rcaction tE) Viral hepatitis

(AJ Alypical Iymphocytes

(B) Aut:r rods in pfOmyelocylcs (e) Birbeck granules in histiocytes (1) Dóhle bodi~ in ncutrophils (E) Hairy cells (F) Hypcn.egmellted neulrophils (G) Lacunar cc1ls (H) Lymphobla'its (1) Megaloblastoid erythroblaslS (J) Myeloblasts (K) Reticulocytes (L) TOxie granularioos in ncutrophils

49. A 38-year-old female ha.. expcricnccd increasing dyspnea A chest radiog.raph demonstrales mcdiastinal widening. A chesl el' sean re\'eals un 8 X 10 cm pOSterior mediastinal mass Ihal impinges on lhe tmellea and esophagus. A mediaslinoscopy is pcrfonned and Ihe mass is biopsicd. Hislologically, Ihere are .~cattel'td Rced-Sternberg cclls along wilh lymphocYles and macrophagcs separatcd by dense collagenous bands. ( )

50. An 18-mooth-old child who has dcvcloped scborTheic skin eruptions is also found to have hepatosplcoomegaly and gencralized Iymphadcnopalhy. He has had rCCUlTCnt

Coone:.y of Dr. Jaalut'linc: Mi,us.

53. A figure skaler who WOI1 gold medals al Ihe rl)2~. 1932. and 1936 Winter Olympic games becanlC progressivcly faligucd in her late fifties. Icading to a workup thm revcalcd a CBC with hemoglobin concenlration of 10.1 8/ dL hcmalocril of 30.5%. MCV of 90 11... platelet l."QUnt of 89,000I1J.L. and WBC count of 31.3OOIJLL From the pe-


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ripheral blood piclure shown in the figure, the mosl likely diagnosis is O O O O O

(A) Infeclious mononucieosis (B) Chronic Iymphocylic leukemia (CLL) (C) Iron deficiency anemia (O) Leukemoid reaclion (E) AcUle lymphobla"lic leukemia (ALL)

54. A serum chemislry panel is performed on a healthy 48-year-old male wilh no complaints olher than his wony· ing aboul gelting older and having callcer. His !otal serum pro!ein concelllration is 7.4 g/dL, and the albumin level is 3.9 g/dL. The serulll calcium and phosphorus levels are nonnal. Urinalysis reveals no Bence Jones proteinuria. A serum protein eleclrophoresis reveals a small (2.8-g) spike of y-globulin, which is delennined !O be IgG kappa by immunoelectrophoresis. A physical examination re\'eals no hepatosplenomegaly or Iymphadenopathy. A bone Illarrow biopsy reveals nonnal cellularily wilh maluralion of all cell lines. Plasma cells constilule about 4% of Ihe maITOw. A bone sean is normal, wilh no areas of increased upmke. Which of lhe following condilions is most likely? O (A) Solilmy plao;macyloma O (B) Waldenslrom macroglobulinemia O (C) Monoclonal gammopalhy of undelennined significance O (O) Heavy-chain disease O (E) Multiple rnyeloma

WHITE CELLS, LYMPH NODES, SPlfEN, AND THYMUS

145

9.5 gldL, hemalocrit of 28.2%, MCV of 94 (L, platelel counl of IIO,OOO/pL, and WBC count of 107,000J,u.L. A bone marrow biopsy shows Ihal the marrow is 100% cellular, with few residual normal hematopoietic cells. Most of Ihe cells in Ihe marrow are large. 1l1eir nuclei have delicale chromatin and seveídl nudeoli. The cytoplasm of these cells hao; azurophilic, peroxidase-positive granules. The mosl likely diagnosis is O O O O O

(A) Chronic Iymphoc-ylic leukemia (CLL) (B) ACUle myelogenous leukemia (C) Acute rnegakaryocytic leukemia (O) Chronic myelogenous leukemia (CML) (E) Acule Iymphoblastic leukemia (ALL)

ANSWERS l. (E) The major finding here is marked grallulocytopellia. All Ihal is left on the peripheral sme."Ir are mononudear cells (remember 10 mulliply Ihe percemages in the differential by the lotal WBC COllnt lo gel the absolule values; .-alher Ihan one cell line being overrepresented, an· other may be nearly missing). Acceleraled removal or de~ slruction of neulrophils could account fOr Ihe selective absence of granulocytes in Ihis case. Overwhehning infeclions cause increased peripheral use or nelllrophils al sites 01' inflammalion. Pelechial hemorrhages can also occur in overwhelming baclerial infections, such as lhose cause<! by Neis~-eria meningÍ1idis. Bleeding is not likely lO be caused by thrombocylopenia, beeause Ihe platelel ooUl1t is normal. Normal bone marrow findings exclude acule Iym~ phoid or myeloid leukemia. In aplastic anemia, Ule maITOW is poorly cellular, and there is a reduclion in red cells, while cells, and plalelel produclion.

BP6 359 PBDó 646

Courtesy uf Dr. Robert W MeKenna, Departrnem of f>athology, Univcrsity of Tcxa~ Southwestel11 Ml>(!ieal School. DlIlIlI.'I. TX.

55. The palienl is a 32-year-old female wilh fmigue, fever, nighl sweats, and painless righl cervical adenopathy. The histologic finding shown here al high power was present in a cervical Iymph nooe lhat was biopsied. This appearance is most likely to be seen wilh O O O O O

(A) Burkiu lymphoma (B) Well-differenlialed Iymphocytic Iymphoma (C) Reactive Iymphoid hyperplasia (D) I-Iodgkin disease, nodular sclerosis Iype (E) Cytomegalovirus infeclion

56. A 22-year-old university sludenl presen!s with easy fatigabilily. A CBC shows a hemoglobin concentration of

2. (n) Shown here are the ramolL" rodlike tubular Bir~ beck granules with characleristic periodicity Ihal is seen in Langerhans cell proliferations. In Ihis case, Ihe skin eruptions. organomegaly, and lesion in the masloid suggest infiltrales in mulliple organs. The diagnosis is muhifocal Langerhans cell hisliocylosis, a disease mosl often seen in children. In one half of these cases, exophthalmos occurs, and involvemelll of Ihe hypothalamus and piluitary stalk leads lo diabeles insipidllS, findings lhal are then called Hand-Schüller-Chrislian disease. ALL in childhood can in~ volve Ihe maITOw, bul does not produce skin or bone lesions. Myeloma is a disease of adulls thal may produce Iylie bone lesions bul not skin lesions. Hodgkin disease is seen in young adults and does nol produce skin lesions Or bone lesions. Tuberculosis may produce granulomalOus disease wilh bony deslruclion, but Ihe macrophages presenl in the granulomas are epithelioid macrophages thal do nol have Birbeck granules.

BP6 383 PBD6685-686 3. (A) This paliem has symploms of hyperviscosily syndrome. such as visual diSlurbances, dininess, and head-


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aches. He also ¡;eem¡; 10 have Raynaud phenomena. His bone marrow is full of pla¡;macylOid lymphocytes that have stored irnrnunoglobulins in Ihe cytoplaslll (Russell bodies). Al! of Ihese suggest Ihal the patient has Iymphoplasmacytic lymphoma (i.e.. WaldenslrQm macroglobulinemia). In Ihb disorder, neoplaslic 13 cells differentiate lO IgM-producing cell¡;, and hence Lhere is a monoclonal IgM spike in the serum. TIlese IgM molecules aggregale and produce hyperviscosily, and some of Ihese agglulinale at low temperalures lo produce cold agglulinin disease. Punched-oul Iylic lesions ¿¡re Iypical of multiple myeloma. another monoclonal gammopathy. However, myeloma does not cause liver and ¡;pleen enlargement. Hypercalcemia occurs with rnye· loma becau¡;e of bone destruction; light chains in urine (l3ence Jone.<; proleins) are also a fealure of mulliple myeloma. A 1(14;18) translocation is characleristic of a follicular lymphoma.

BP6381

PBD6 666-667

4. O») Marked leukocylosis and immaLure myeloid cells in Lhe peripheral blood can repw;enl an exaggeraled re+ sponse lo infection (i.e., leukemoid reaclion) or be a manifestalion of CML. However, Ihe leukocYle alkaline phosphalase score i¡; high in Ihe more differenlialed cell population seen in reactive leukocylOsis, whereas in CM L, the leukocyte alkaline phosphalase SL"Ore is low. TIle Phi ladelphia chromosome (universally present with CML) is. absenl with leukemoid reaclions. Hair)' cell leukemia is. acL'Ompanied by peripheral blood leukocytes Ihal rnark with lartrale-resislanl acid phosphatase. Hodgkin disease is nol characlerized by an increased WBC counL. ALL i¡; a dis+ ease of children and young adults, and lhe Iymphoid cells do nol have leukocj'le alkaline phosphatase.

BP6 377

PBD6 681

5. (E) Burkiu and Burkiu-like Iymphomas can be seen sporadically (in young persons), a<; an endemic form in Africa (in children), and in associalion with HIV infection. AII fonns are highly associated wilh translocalion¡; of Ihe l/1)'c gene on chromosome 8. 111 Ihe African fonn and in HIV-infecled patien!¡;, the <..'Clls are lalently infecled wilh EBV. bUl sporadic cases are EBV negalive. Involvement with Ihis form of lymphoma is Iypically eXlranodal. Diffuse large cell Iymphomas are mosl COllllllon in adults, a<; are follicular Iyrnphorna<;. They do not carry the 1(8; 14) tran¡;localion. Acule lymphoblaslic IYlllphomas may be seen in boys. al lhis age, but the mass is. in Ihe mediaslinum, and the Iymphoid cell¡; are T cells. Plasmacytoma<; appear in older adulls and are nol likely to produce an abdominal mass..

BP6368 PBD6 662-663 6. (n) Diffuse large B-cell Iymphoma occurs in older individuals. and frequently presel1l¡; a.. localized disease wilh exlranodal involvemenl. particularly of Ihe Waldeyer ringo The slaining pallern indicales a B-cell proliferation (CD19', CDIO'). T-cell (CD3) and monocylic (CDI5) markers are absent. TdT can be expressed in B-lineage cells al an earlier slage of maluration. Small Iymphocylic Iymphoma is also a B-cell neoplasm, bUI it manifests with widespread Iymphadenopalhy, liver and spleen enlargemenl, and Iymphocytosis. Lymphoblaslic lymphoma is. a T-

cell neopla<;m Lhat occurs typically in Lhe mediastinum of children. Hodgkin disease is characterized by Reed-Slernberg cells. In chronic lymphadenilis. the lymph node has rnany cell types-macrophages, lymphocyte<;, and plasma cells. A monomorphous infiltrale is Iypical of non+Hodgkin Iymphomas.

BP6 366-367

PBD6 654-656

7. (E) This palienl has polycythemia vera. TIüs is a myeloproliferative disorder chamcteri7.ed by an increased RBC mass, with hemalocrils. typically exceeding 60%. Allhough the increa¡;ed RBC ma<;s i¡; responsible for mosl of the symptom¡; and signs, Ihese palienls have Ihrombocytosi¡; and granulocytosis a.<; wel\. TIlis occurs because, like olher myeloprolifenllive disorders. polycylhemia vera results from Iransfonnatioll of a multipotenl slem cel!. The high hernatocril causes an increase in blood volume and dislenlion of blood vessels. Along wilh abnonnal plalelet fUlle+ tion, this condilion predisposes lO bleeding. Abnormal plalelet function may also predispose lO thrombosis. His prurilus. and peptic uleeration seem to be Ihe resull of Ihe his.lamine release from basophils. In ¡;ome patients. Ihe di¡;ease "bums out" lo myelofibrosis. A few patiem¡; "blas.! out" inlo acute myelogenous leukemia, and others develop CML. Myelodysplas.tic s.yndromes and myeloproliferalive disorders, such as es¡;elllial thrombocYlosis. are nOl accompanied by such an increase in red cell mass. ErYlhroleukemia is no! typically accompanied by such a high hemalocrit.

BP6378-379

PBD6682-683

8. (C) This palien! has developed a myelodys.pla¡;ia, charaClerized by a ceUular marrow in which Ihere are maturalion defecls in multiple lineages. This diagnosis is supported by the presence of ringed sideroblUSls, megaloblasl¡;, abnormal megakaryocyles, and myeloblasts in the marrow. Because Ihe hematopoielic cells fail lO mature normally, Ihey are not released inlo Ihe peripheral blood. The palien! has pancylopenia and is susceptible !o infections. Myelodysplas.ias are c10nal ¡;tem cell disorders Ihal develop de novo Or after chemotherapy with alkylating agents, as in Ihis case. The presence of chromosomal delelions such as 5q are markers of püSt-ther<lpy myelodysplasias. llle rnorphologic abnormalities in Ihe marrow are not seen in any olher listed condilion.

BP6376

PBD6 678-679

9. (A) Essenlial Ihrornbocythernia is a rnyeloproliferalive disorder. As wilh all myeloproliferative disea<;es, Ihe transfomlalion occurs in a rnyeloid stem cel!. In Ihis fonn of myeloproliferative disea¡;e, Ihe dominanl cell type affected is Ihe rnegakaryocyle, and hence there is Ihrombo<.-ytosi¡;. However, other myeloprolifemlive disorders can also be accompanied by an increa¡;ed platelet counl. The diagnosis of essential Ihrombocytosis can be made after other cau¡;es for reaclive thrombocylOSis. are excluded and if the bone marrow examination shows increased megakaryocyles without evidence for leukemia. TIle Ihrobbing, burning pain in Ihe exlremities is caused by aggregales. of platelets thal occlude small aJ1erioles. The major rnanife<;!ation of !his disea"e is Ihrombolic or hemolThagic crises.

PBD6 683


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147

10. (E) He has Ihe African variely of Burkiu Iymphoma, a B-cell Iymphoma thal lypically appears in the maxiJla or mandible of lhe jaw. 111is particular neoplasm is relaled lo EBV infeclion. BP636B-369 PBD6662-663

somelimes associated wilh a thyrnic lumor. In about one half of such cases, resection of Ihe thymic lumor relie\'es Ihe red cell aplasia, suggesting same auloimmune mechanisms as Ihe cause of red cell aplasia. PBD6 632, 693

11. (J) Lymph nodes draining from a cancer oflen demonstmle a reactive paltern, with dilaled sinusoids thm have endOlhelial hypertrophy ¡¡nd are filled wilh histiocytes (Le., macrophages). Sinus histiocytosis represents an immunologic response lo cancer antigens. Not all enlarged nooes are caused by metastatic disease in cancer palienls. BP6362-363 PBD6 650

17. (C) Polycythemia vera is a neoplastic disorder of myeloid stem cells that lend lO dirrerenliate predominamly along lhe erythroid lineage, giving rise lO polycythemia. The neoplaslic erythroid progenitor cells Tequire eXlremely small amoums of erythropoietin for survival and prolifemtion, and hence the levels of erythropoietin are virtually undetectable in polycythemia vera. In all other conditions, erythropoietin levels are elevaled lo produce excess red cells. Erythropoielin secrelion is Iriggered by alloxia in high-altitude dwellers alld persons wilh cyanolic heart di¡;ease. Renal tumOrs produce erythropoietin and lrigger a paraneoplastic erylhrocylosis. In dehydration, Iransiem polycylhemia is caused by hellloconcentration. This does not affeet normal erylhroJXlielin secrelion. BP6378-379 PBD6 6B2-6B3

12. (B) Multiple myeloma produces mass lesions of plasma cells in bone Ihat lead lO Iysis and pain. The skull radiograph shows typical punched-oul Iylic lesions, produced by expanding ma~ses of plasma cells. Bence Jones proteinuria can damage the tubules and give rise to renal failure. Multiple myeloma can be complicated by AL amyloid, which call also lead ro renal failure. Patients wilh myeloma often have infeclions wilh encapsulated bacteria because of decreased production of 180, required for opsonization. Granulomalous disease (which is no! produced by pneumococcus) may involve the marrow but usually does not produce such sharply demarcated Iylic lesions. Nodules of small Iymphocyles suggest a small cell IYlllphocytic leukemiallymphoma, which is not likely to produce Iytic lesions. Reed-Sternberg cells suggesl Hodgkin disease. Blasts suggesl a leukemic process. BP6 380-382 PBD6663-666 13. (C) Interleukin-S acts as an eosinophilic chemOlaclic faclor that make.<; an eosinophilic cellular component part of lhe mixed cellularily and nodular sclerosis types of Hodgkin disease. In Cünlmsl, Ihe lransforming growth faclor-{3 (TGF~{3) secreled by eosinophils promoles Ihe fibrosis Ihat is part of nodular sclerosing Hodgkin disea<;e. PBD6674 14. (H) The mucosa-associated Iymphoid tissue (MAL1) lesions in Ihe stomach can be associated wilh Ihe presence of H. 1)'lor; infeclion. Although Illonodonal (like a neopla<;m), Ihese MALT Iympholllas can regress wilh anlibiolic lherapy for the H. pylori. BP6 36B PBD6 66B 15. (O) Non-Hodgkin lymphornas of the large diffuse Bcell type can be associated wilh HIV infection and define the acquired immunodeficiency syndrome (AlDS). AIDS Iymphomas tend ro be extranodal, and Ihe large cell type can also involve Ihe cenlral nervous system; they have a poor prognosis. In approximalely 50% of cases the sys~ lemic diffuse large Iymphomas contain the EBV genome. Virtually 100% of A1DS-a<;sociated cenlral nervous system Iymphoma<; are infecled with EBV. BP6366-367 PBD6 661-662 16. (L) This palient has arare disorder called pure red cell aplasia, chamclerÜ,ed by selective suppression of Ihe erythroid lineage in Ihe bone marrow. This curious enlily is

18. (C) Chronic infeclions and chronic inflammalory condilions, such as lung abscess, can lead lo an expansion of lhe myeloid precursor pool in the bone marrow. This is manifesled as neutrophilic leukocylosis. Acute viral hepalilis, unlike acule baclerial infections, does nol cause neulrophilic leukocytosis. Glucocorticoids may increase the release of marrow storage pool cells and diminish exlravasalion of neutrophils inlo tissues. Vigorous exercise can transiently produce neulrophilia fTom demarginalion of neulrophils_ Wilh acute myelogenous leukemia, Ihe marrow is filled wilh bla<;ts, nol maturing myeloid elemems. BP6359 PBD6 647 -648 19. (A) This H1V~positive palienl has an extranodal infiltralive mass in Ihe ileum Ihal is made up of B cells (CO 19+). This is a diffuse large cell Iymphoma of 13 ceUs. These tumors conlain Ihe EBV genollle, and it is Ihough! Ihat immunosuppression allows unregulaled proliferalion and neoplastic Iransformation of EBV-infeeted B cells. HIV is nol seen in normal or neoplaslic B cells. HHV-8, also called Kaposi sarcoma herpesvirus, is found in Ihe spindle cells of Kaposi sarcoma and in body cavity B---cell Iymphomas in AlDS patienlS. HTLV-I is related to HIV-I, alld il causes adull T-<:ell leukemiallyrnphoma. CMV is not known lo cause any tumors. BP6 367 PBD6 661-662 20. (B) The c1inical history. Ihe peripheral blood smear. and Ihe phenolypic markers are characteristic of chronic lymphocYlic leukemia. This is a c10nal B-cell neoplasm in which immunoglobulin genes are rearranged and T-cell receptor genes are in germline configuralion. The 1(9;22) is a fealure of chronic myeloid leukemia. The t(8;14) lranslocalion is Iypical of Burkitt Iymphoma; Ihis occurs in children al extranodal siles. The 1(14; 18) translocation is a feature of follicular Iymphomas. The.<;e are dislinctive B-<:ell tu~ mors that involve the node.<; and produce a folJicular paltemo The Iymphoma cells can be presem in blood, but they do nol look Iike malure lymphocytes. BP6 377 -378 PBD6 658-659


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21. (A) The chamcleriSlic "punched-our" bone lesions of mulliple myeloma seen on mdiographs reslllt from areas of bone Iysis wilh plasma cell proliferation. Thc bone marrow aspirnle shows plasma cells. The monoclonal poPlllalion of plasma cells oflen produces a monoclonal serum "spike" seen wilh serum or urine prolein eleclrophoresis. Palients may have hyperca1cemia and an increased serum alkaline phosphatase leve!. ll1e neoplaslic cells are generally well differenlialed. wilh fealures such a.. a perinuclear "hof," similar to normal pla"ma censo The 1(9;22) tmnslocalion is Ihe Philadelphia chromosome seen wilh chronic myeloge4 nous leukemia (CML). CML and olher myeloproliferalive disorders may be accompanied by a Ihrombocytosis bUl are unlikely lo produce mass lesions Ol" bony deslruction. BP6380-382 PBD6663-666 22. (E) The bands of fibrosis are Iypical for Ihe nodular sclerosis Iype, which is most commonly seen in young adults, particularly females_ Involvement of one group of Iymph nodes places this in slage 1. Mediastinal involvemenl is common. MosI of such cases are stage I or 1]. The prognosis of such early slage cases is good. BP6369-372 PBDó 672-675 23. (E) Acule enlargement of nodes Ihal are painful suggests a reaclive condilion, nol a neoplastic process such as a Iymphoma or a leukemia. In children. acute Iymphadenilis is common. There are many illfectious processcs thal can give rise lO this finding. particularly bacterial infeclions. Sarcoidosis is a chronic granulomatous process characleriu~d by Ihe fonnation of noncasealing granulomas. Follicular Iymphomas are neoplasms of B cells Ihal efface lhe nonnal architecture of Ihe Iymph nodes. These IUmOI'S do nol occur in children. Cal scmtch disease may produce sarcoid-Iike gmnulomas with stellate abscesses. 8P6361-362 PBD6649 24. (O) This is acute promyelocylic leukemia (M3 class of acute myelogenous leukemia). As in Ihis case, many patients develop disseminaled inlravascular coagulation. The I( 15; 17) lranslocalion is characlerislic of Ihis disease. lt resllltS in the fusion of Ihe relinoic acid receptor gene on chromosome 17 wilh the promyelocytic leukemia gene on chromosome 15. The fusion gene results in elaboration of an abnonnal relinoic acid receptor lhat blocks myeloid differenlialion. Therapy wilh relinoic acid (vitamin A) can alleviale Ihe block and induce remission in many palienls. The 1(8:21) abnormalily is seen wilh Ihe M2 varianl of acule myelogenous leukemia. ll1e 1(9:22) translocalion gives rise lo Ihe Philadelphia chromosome of chrollic myelogenous leukemia. A t(l4:18) karyolype suggests a follicular Iymphoma. The 1(8:14) translocalion can be seen wilh a Burkitt Iymphoma. BP6 375 PBD6676-678

Ihe WBC count is quite high; Ihe peripheml blood conlains sorne myeloblasls. bUI olher slages of myeloid differenlialioll are also detected. In idiopathic thrombocYlopenic purpura, only Ihe plalclel COlllll is reduced. because of anlibody-medialed deslruclion of plalclcts. An acule myelogenous leukemia is a disease of young lo middle-aged adults, and Ihere should be peroxidase-posilive myeloblasts and phenolypic fealUres of myeloid ceJls. Chronic Iymphocylic leukemia is a disease of older adults, with many small circulaling malurc B Iymphocylcs. 8P6374-375 PBDó 656-658 26. (E) Infectious mononucleosis is Iypically an aculc. self-limited EHV-<:aused disease thal gives rise lo a mild splenomegaly. Splenic enlargement regresscs when tbe palielll reco\'ers. AIl olhers are chronic disorders wilh markedly enlarged spleens. In CML and myelofibrosis. the spleen is Ihe site of proliferation of neoplaslic myeloid slem cells. In Gaucher disease, splenic macrophages slore glucocerebrosides. Kala-a7..ar is a fonn of visceml Leishmaniasis caused by Leishmallia donovani and L donovani chagasi. These parasites lodge in Ihe reliculoclldothclial syslem, including in Ihe spleen. causing ma~sive enlargemenl.s. 8P639O P8D6688-689 27. (A) AlI Iymphoid Ileoplasms arc derived from a single Iransfonned cell and are Iherefore monoclonal. Monoc10nality in B-cell neoplasms. which comprise 80% lo 85% of all Iymphoid neoplasms, can oflen be demonslraled by staining for lighl chains. Populatíons of normal or reactive (polyelonal) B cells conlain a mixlure B cells expressing kappa and lambda light chaillS. Sorne Iymphoid neoplasms have a follicular pattern, and olhers do nol. A normal paltern of follicles may be absellt if Ihe nocle is involved wilh sorne inflammalory cOlldilions or wilh immune suppression. A proliferalion of capillaries is typicaJly a benign, reaclive process. Thc C030 antigen is a marker for actívaled T and B cells. Plasma cells are variably present in reactive condilions, but Iheir absence is nol indicalivc of malignancy. BP6362-363 PBDó 650-653

The rnpid expansion of lhe marrow caused by proliferntion

28. (A) Of tbe lesions listed here. Iymphoblaslic Iymphoma and Burkitt Iymphoma occur in a much younger age group. Burkill Iymphoma has a 1(8;14) lranslocalion. Thc remaining three occur in an older age group. Of Ihese. small Iymphocytic Iymphoma presellls with absolutc Iymphocylosis and a peripheral blood picrure of chronic Iymphocytic leukemia. FollicuJar Iymphoma has a diSlinCI and characteriSlic tmnslocalion 1(14;18) involving Ihe be/·2 gene. In conlrasl, mantle cell Iymphoma has lhe 1(11;14) Imnslocalion, which activales cyelin DI (be/./) gene. ll1ese tumors do not respond well lO chemotherapy. BP6 366 P8D6 667-668

of blasts can lead lo bone pain and tendemess. Fealures supporting an acule leukemia are anemia. Ihrombocytopenia, alld presence of blasts in lhe peripheral blood and bone marrow. Anemia and IhromhocYlopenia result from suppression of normal hemalopoiesis by Ihe leukemic clone in Ihe marrow. The phenolype of COI9\ C03-, s[g' is Iypical of pre-B cells. TdT is a marker of early T· and Bcell-type Iymphoid cells. CML is a disease of adults, and

29. (A) The features suggeSI Hodgkin disease, mixcd cellularily Iype, which lends lO affect older males. As in all olher forms of Hodgkin disease, Ihe Reed-Slernocrg cells and variants slain with COI5. These cells also express C030. an aClivalion marker on T cells, H cells, and monocyles. C1inical symptoms are frequent in lhc mixed ccllularity Iypc of Hodgkin disease, and Ihis hislologic type

25.

(E) This is a childhood ALL of lhe pre-B cell Iype.


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149

lends to present in advanced stages. The pain associated wilh alcohol consumption is a peculiar panmeoplastic phenomenon wilh Hodgkin disease. The Reed-Stemberg cells make up a relatively small percentage of Ihe tumor mass, with most of the cell population collsisting of reaclive cells such af> Iymphocytes. plasma cells, macrophages, and eosinophils. Immunoblasts suggest a B-cell proliferalion. Epithelioid cells are seen in granulomatous ¡nflammatory reactions. Neutrophils accumulate al sites of acute inflammation.

negalive by karyotyping and by RSH, molecular analysis reveals hcr-ah/ rearrangemenls. This rearrangemenl is considered a diagnoslic crilerion for CML. This is a disease of pluripolenl stem cells Ihat affects al1 lineages, but Ihe gmnulocytic precursors expand preferenlially in Ihe chronic phase. Follicular Iymphomas have a t(l4;18) k.1.ryolypic abnonnalily involving the hcl-2 gene. In general, Hodgkin disease and myelomas do not have characleristic karyotypic abnormalities. Acule promyelocylic leukemias often have the 1(15;17) abnormalily.

BP6370-371

BP6 377

PBD6672-676

30. (e) She has evidence for an autoimmune disease, most likely syslemic lupus erylhematosus. This can be accompanied by monocytosis. (CYlOpenia.. can also occur in systemic lupus erythematosus bccause of auloanlibodies against blood elements La fonn of type 1I hypersensilivity].) Eosinophilia is a fealure more often seen wilh allergic conditions, parasilic infestations, and chronic myeJoid leukemia (CML). Thrombocytosis usually occurs with nooplastic disorders of myeloid stem cells, such as CML. BasophiJia occurs infrequenlly bul !llay be seen with CML.

PB6 359

PBD6 64B

31. (B) MultipJe myeloma is composed of abnormal plasma ceJls Ihat tend lo retain Ihe ability lo secrete immunoglobulills. Heavy and light chain components can be produced. The Jight chaills are excreted in Ihe urine and are known as Bence Jones proleins. Serum protein (S1') electrophoresis is used lO screen for Ihe presence of a monoclonal immunoglobulin (M protein). 1'olyc1onal IgG in normal serum (denotcd by the arrow in the illuslralion) appears as a broad band; in conlrasl, serum from a palienl wilh multiple myeloma contains a single shmp protein band in this region. The suspecled monoclonal immunoglobulin is Ihen confinned and characlerized by immuno-fixation. In this procedure the eleclrophoresed proteins within Ihe gel are reacted with specific anlisera. After exlensive washing, only proleins cross*linked by Ihe antisera are relained in Ihe gel, which is Ihen stained for prolein. The sharp band in Ihe immunoglobulin region of the patienl's SI' is recogni7.ed by antisera againsl IgG heavy chain (G) and kappa light chain (K), indicating Ihal this band is an 19GK M prolein. The levels of polyc1onal IgG, IgA (A), and lambda lighl chain (A) are also decreased in the palienl senun relalive lo nonnal semm, a common finding in multiple myeloma. The TdT-positive circulating blasts are seen in lymphoblaslic leukemias. The 1(8: 14) translocalion is Iypical for a Burkitt Iymphoma. Amyloidosis, reactive and primary, can give rise lO renal failure. In primary amyloidosis, Ihe amyloid is derived from irnmunoglobulin lighl chains, and paliel11s may have a monoc1o-nal H-cell proliferalion. However, reactive amyloid is made up of nonimmunoglobulin proteins. A markedJy increased hemalocril may suggest polycylhemia as pan of a myeloproliferative process.

BP63BO-382

PBD6 663-666

32. (B) This is the Philadelphia chromosome, or Phi, that is chamcteriSlic ror CML. This kal)'otypic abnormalily can be found by cylogenetic lechniques, including Auore5Cence in silu hybridizalion (FISH). In Ihe few cases that appear

PBD6680-682

33. (C) This palient has follicular Iymphoma, Ihe mosl common form of non-Hodgkin Iymphoma among adults in Ihe United States. Men and women are equally affecled. The nooplastic B cells mimic a populalion of follicular center cells and hence produce a nadular or follicular patlern. Nadal involvemenl is often generalized. bul exlrallo-dal involvemelll is uncornmon. The 1(14;18) Imnslocation is characletistic. It causes overexpression of the hcl-2 gene, and hence lhe cells are resistanl to apoplosis. In keeping wilh this, follicular Iymphomas are indolenl lumors that conlinue lo accumulale cells over 7 lo 9 years. In Hodgkin disease. there are few Reed-Slemberg cells surrounded by a reactive Iymphoid population. The Iymphoid (Xlpulation in acule Iymphadellilis is reaclive, and Ihere is no bone marrow involvement. Mantle cell Iymphoma is also a B-cell tumor; il is more aggressive Ihan follicular Iymphoma and is Iypified by Ihe 1(11;14) Iranslocalion in which Ihe cyclin DI gene (Ix/-/) if> overexpressed. In loxoplasmosis, there should be a mixed population of infiammatory cells with some necrosis.

BP6364-366

PBD6659-661

34. (C) This is Ihe M3 varianl of acule myelogenous leukernia, wilh many promyelocylcs containing prominent azurophilic granules and short, red, cYloplasmic, rodlike inclusions calle<! Auer rods. Release of the granules can ITigger Ihe coagulation cascade, leading to DIe. Leukemias do nol lend lo produce mass lesions or erode bone, as does rnulliple rnyeloma. Chronic renal failure is nol a typical feahlre for leukemias or Iymphomas. Small oowel obstruclion from Iymphoma can OCCUl", Iypically from E-cell maIignancies such as Hurkilt Iymphoma or ditfuse large B-ceIl Iymphoma. H. pyluri infection, which is a risk faclor for peplic ulcer clisease, can aloo be involved in Ihe pathogene* sis of gaslric B-cell lymphoma".

BP6374

PBD6675-677

35. (O) The pale, lan to yellow, firm areas are infarcts. These lesiolls are eilher wedge-shaped and based on Ihe capsule 01' more irregularly shaped wilhin the parenchyma. Emboli in the systemic arterial circulalion may mise fmm vegelalions on cardiac valves in a paliem with infective endocarditis. These can lead to splenic infarclion. Emboli eXiling the aona at the celiac axis generally take the straight roule lo the spleen. Kidneys and brain are other frequem siles for systemic emboli to lodge. Melaslases may increase Ihe size of the spleen oomewhal but are uncommon in the spleen and are nol likely lo be accompanied by signs of infection. Allhough acule myelogenous leukemia and Hodgkin disease can increase Ihe Si7.e of Ihe spleen,


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therc are typical1y no focal lesions-only unifOlm infiltration of the parenchyma. Likewise, Ihe congeslive splenomegaly with cirrhosis and ponal hypenension does nol produce focal splenic lesions. There should be scaltered gnmulomas Ihat are rounded and lan wilh granulomatous diseases of Ihe spleen, such as histoplasmosis. PBD6 6B9

anl of acute myelogenous leukemia (i.e., promyelocytic leukemia) has many promyelocytes filled with az.urophilic granules, making them slmngly peroxidase positive. Ery4 thmleukemia is rdre and is accompanied by dysplastic erythroid precursors. BP6376 PBD6676-679

36. (A) She developed severe nemropenia wilh pancytopenia fmm drug loxicily, which predisposed he.. to sepsis. Aspergillosis is a cause for pulmonary granulomas, and neutropenia is a significanl ..isk faclor. BP6359 PBD6646-647

41. (A) Three markers strongly favor a very good prog· nosis: early pre-B ceJl type, hyperdiploidy, and an age between 7 and 10 years. COllversely, poor prognostic rnarkers are T-cell phenolype; an age younger Lhan 2 years; presence of 1(9;22); and presentalion in adolcsccnce and adulthood. BP6 374 PBD6 657-658

37. (1) The eosinophilia suggesls a parasitic infeslation. Persons who are immunocompmmised may have superinfeclÍon and disseminalion with slmngyloidiasis. BP6 359 PBD6 337. 64B 38. (A) This patienl has hairy cell leukemia, an uncommon neoplaslic disorder of B cel1s (C020~). These cells infiltrate lhe spleen and marrow. Pancylopenia results from poor production of hemalopoielic cells in the marrow and sequeslration of Ihe mature cells in Ihe spleen. There are two characterislic features of this disease: Ihe presence of hairy pmjeclions fmm neoplaslic leukocytes in the peripheral blood smear and tartrale-resistanl acid phosphatase in the neoplastic cells. Auer rods are seen in myeloblasts in acule myeloblaslic leukemia. The Phi chmmosome is distinClive for CML. Toxic gnmulations in neutrophils are mosl oflen seen in overwhelming baClerial infections. A monoclonal IgM spike is a feature of Iymphoplasmacytic Iymphoma (i.e., Waldenstrom macroglobulinemia). BP6 378 PBD6 668-669 39. (C) The smear shows large. "atypical" Iymphocytes that are seen in infeclious mononuclcosis and other viral infections, such as those caused by CMV. These atypical cel1s are large Iymphocytes with abundant cytoplasm and a large nucleus with fine chmmatin. lnfeclious mononucleosis is cause<! by EBV and transmiued by close personal contacto Disorders of glohin chain synthesis affecl red hlood cells, a~ in the lhalassemias. lnfeclious mOllOnucleosis is not known as a lransfusion-associaled disease. Likewise. injection drug use is typically nol a risk factor for infeclious mononucleosis bur is a risk for baclerial infec4 lions, HIV infection. and viral hepatitis. Eating raw oyslers is a risk faclor for hepatitis A, because the hepatitis A virus is concentrated by Ihe oysters from polluled sea water. BP6360 PBD6 371-373 40. (E) This palielll has an "aleukemic" leukemia, whereby the peripheral blood counl of leukocytes is nQt higb, but Ihe leukemic blasts fil1 the marrow. These blasls sllow features of monoblasts because lhey are pemxidase negalive and nonspecific eslera<>e positive. This patient has an M5 leukemia. characterized by a high incidence of lis· sue infiltralion and organomegaly. ALL is typically seen in children and young adults. Acure megakaryocytic leukemia is rdre and typically accompanied by myelolibrosis. and lhe blast~ react wilh platelel-specific antibodies. The M3 vari-

42. (A) TIle involvemenl of skin and the presence of Iymphocytes with complex cerebriform nuclei in the skin and Ihe blood are features of cutaneous T-cell Iymphomas. These are malignancies of CD4'" T cells that may produce a IlIlTIor-like infiltralion of the skin (i.e., mycosis fungo¡des) or a leukemic piclure without tumefaclion in lhe skin (Le., Sézary syndmme). Cutaneous T-cell Iymphomas are indolent tUI11QfS, and patients have a median survival of 8 lO 9 years. The other phenolypes provided here are Ihose of malure B cell~ with CDI9+, slg+; 1Il0nocyles/granulocytes with CD33"', COI3'; and neoplastic B cells in chronic Iymphocytic leukemia with COI9', C05~. PBD6 670 43. (B) This patienl has c1assic featllres of myelofibmsis with myeloid metaplasia. This lIlyeloproliferative disorder is lllso a stem ceIl disorder in which neoplastic megakaryocytes secrele fibrogenic faclor.'; leading to marrow fibrosis. The neoplastic clone Ihen shifts to rhe spleen, where il shows trilineage hematopoietic proliferalion (i.e., cXlramedullary hematopoiesis), in which megakaryocytes are prominenl. The marrow fibrosis and the extrarnedul1ary hematopoiesis in the spleen fail to regulate orderly release of leukocytes into the blood. Therefore, the peripheral blood has immature red cell and white cel1 precursors (i.e.. leukoerythroblaslic picture). Tear-dmp red cells are misshapen RBCs Ihal are seen when marrow undergoes fibmsis. Marrow injury can have olher causes as well (e.g., metastalic tllmors, irradiation). TIlese can also give rise to a leukoerythroblaslic picture, bul splenic enlargement with Irilineage proliremtioIl is not usual1y seen. The olher causes men~ tioned-Hodgkin disea~e and H. capSUlalll111 infectiotlcan cause splenic enlargement but nol marrow librosis. BP6379-380 PBD6683-685 44. (B) This patielll has c1inical and morphologic fealures of diffuse large cell Iymphoma of H cells. These tumors often involve extranodal sites, show large anaplaslic lymphoid ceJls thal involve Ihe tissues diffusely, and conlain bcl-ó gene rearrangemems. Their c1ínical course is aggressive. and Ihey are rapidly fatal if untreated. However, with intensivc chemotherapy, 60% to 80% of paliems achieve complete remission. and about 50% can be cured. BP6 366-367 PBD6 661 -662 45. (D) This patienl carne with a classic history of CML, confirmed by the presence of differenl stages of myeloid


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WHITE CEl1S, lYMPH NODES. SPlfEN. ANO THYMUS

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differenlialion in lhe blood and by the presence of Ihe Philadelphia chromosome. He wenl inlo a remission and !hen el1lered a blasl crisis involving B cells (CDl9+). 1ñe faet thal lhe B cells carry lhe original Phi chromosome and sorne additional abnormalities indicates lbal the B eeUs and lhe myeloid cells belong to the same clone. The best explanation is lhat the inilial transfonning evenl affected a pluri~ poIent slem cell that differenliated along the myeloid lireage to produce a picture of CML Analysis. even al Ibis stage, reveals lhat lhe molecular counlerpart of Ihe Phi chromosome-Ihe bcr-abl rearrangemenl-affects all line· ages. including B cells, T cells, and myeloid ceUs. With lhe evolulion of lhe disease. additional mUlalions aceumuIale in lile stem cells. which then differentiale mainly along B lineages. giving rise lO B-Iymphoblastic leukemia.

alypical Iymphocytes are CD8 I T cells that are activated by EBV4infected B reUs. There is no iocrease in basophils, eosinophils. or monocytes in infectious mononucleosis. 1ñe 1(9;22) gives rise to lhe Philadelphia chrom~me charnclerislic of chronic myelogenous leukemia.

BP6 377

BP6 372

PBD66l'O-6B2

46. (A) The age and mediaslinul local ion are typical for a Iymphoblaslic Iymphoma involving Ihe Ihymus. This lesion is in lhe spectrum of acule Iymphoblaslic leukemia or Iymphoma (ALL). Mast ALL cases with Iymphomatous presentalion are of Ihe pre-T cel! type. This is supponed by the expressioll of Ihe T-celJ markm C02, C05. and COI. Tóf is a marker of pre--T and pre-B ceUs. A Burkiu Iymphoma is a B-cell Iymphoma thal may also be seen in adolescents but in the regiOll of the jaw or abdomen. Nodular sclerosing Hodgkin disease does occur in the mediasli~ numo but il iu\'olves mediastinal nodes, not lhymus. The histologic fealures of Hodglón disease include the presence of Reed-Slemberg reUs, and this varianl has fibrous bands inteTsecting the Iymphoid cells. Mantle ceH Iymphomas and follicular Iymphomas are B-cell lumors usually sten in older patients. aOO they do no! invol\'e lhe thymus.

BP6367

BP6 360-361

PBD6 371-373

49. (G) 1ñe lacunar ceUs. along wilh the Reed-Slemberg ceUs. aI"t iTKiicative of Hodgkin disease. and lile fibroos bands suggest lhe nodular sclerosis Iype. Lacunar rells have mllltilobed lluclei conlaining many SIllaU nueleoli. 1l1ese celLs have artifaetual r-elraclion of the cyloplasm arollnd the nucleus, gi"ing these cells Iheir distioclive ap-pearn1lce. The nodular sclerosis type of Hodgkin distase is more comlllOn in women.

PBD6670-674

50. (C) The child has Leuerer-Siwe disease. a form of Lallgerhans cel! hisliocylosis. The Birbeck granules are a distillclive lealure idenlified by eleclroll microscopy thm are found in Ihe cyloplasm ol" lhe Langerhans ceUs.

BP6383 PBD6685-686 51. (O) Toxic granulatiolls. which are coarse and dark primary granules, and DOhle bodies. which an: p<llches of dilaled endoplasmic reticulum, represen! reactive changes of neulrophils. These changes are most indicalive of o\'erwhelming inflammalory conc!ilions soch as baclerial sepsis. Leukemia, granulomatous infections. or viml infections do no! cause loxic changes in neutrophils. Infectious mononucleosis is accompanied by an increase in "atypical" Iymphocytes.

PBD6 648-649

PBD6 6S4-6<\6

47. (B) This patient has polycythemia vern. The symp-loms resull from the increased hematocrit and blood vol~ ume. Undeteclable erythropoielin in Ihe face of polycylhemia is characteristic of polycythemia vera. Polycythemia vera is a myeloproliferative disorder in which Ihe neoplaslic myeloid cells differenliate preferenlially along Ihe eryIhroid lineage. However, other lineages are also aftecled, and hellce there is leukocylosis and Ihrombocylosis. These patients are Phi chromosome negalive. Umreated, Ihese patients die of episodes of bleeding or thrombosis-hoth related lO disordered platelet flloclion and the hemodY4 namic effcelS on distended blood vessels. Trealment by phlebotomy reduces the hemalocril. With this trealmenl. 15% to 2~ of lhe palients characleri5lically lransform into myelofibrosis wilh myeloid metaplasia. Termination in acute leukemia., ulllike in chronic myeloid leukemia., is rareo When il occurs. it is an acule myeloid leukemia. not Iymphoblastic leukemia.

BP6378-379 PBD6 682-6B3 48. (O) In patielllS wilh infectioos monOllucleosis. mullipie c100es of B cells are infected by EBV. lbe EBV genes cause prolifemlion and aetivation of B «lis. and hence there is polyclonal B-cell expansiono These B ceUs secrete anlibodies with several specificities. including those Ihat cross-react with sheep red blood cells. lt is these heterophile antibodies Ihal give a \Xlsilive monospot lest. The

52. (B) The peripheral eosinophilia set:n bere is a feature of allergie dison:lers. iocluding I)'pe I hypersensitivilY reactions. Extrinsic asthma is a common disorder in which eosinophilia may appear. Infestations with parasiles thal invade tissues are also knowll lO produce significanl eosinophilia. Sepsis fIlosl commonly results in a marked neulrophilia and left shift. Wilh CML, the 10lal WBC eounl is Iypically high. Although Ihere may be incn:ased eosino-phils in CML, Ihe peripheral blood also shows basophils, metarnyelocytes, myelocytes, and a few blasts. A leukemoid reactloCl may appear similar to CML. but lile leukocyle alkaline phosphatase level is high in the former, and there is usually no eosinophilia. Viral infections are IypiealIy nO( accompanied by marked increases in the WBC counl.

BP6 359 PBD6 648 53. (B) Sonja Henie died froro complications of CLL. in which theTe are increased numbers of circulaling small. round. malure I),mphoc),tes with scant c)'toplasm. 1bese cells are seen in the blood smear. 1be cells express the CDS marker and lbe pan B-cell mari.:ers COl9 aoo C020. Most cases ha,'e a course of 4 lo 6 years befare dealh. and symptoms appear as Ihe leukemic cells begin lo fill lile marTOw. 111 sorne patienlS. Ihe same smaU Iymphocytes appear in lissues. in which case the condilioll is known as small Iymphocylic Iymphoma. The Iymphocytes seen with infectl011s mononucleosis are "atypical Iymphocytes" lhal


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have abundanl, pale blue cytoplasm thal seems lo be indentetl by surrounding RBes. The RBCs in iron deficiency anemia are hypochromic and microcytic. but the WBCs are not affeeled. Leukemoid reaetiolls are typically of the myeloid type, and the peripheral blood eontains immature myeloid cells. The WBC count can be very high, but the plalelet counl is normal. ALL is a disease of ehildren and young adults, charaCteri7,.ed by prolifemlion of lymphoblasts. These cells are much larger Ihan the cells in CLL and have nucleoli. BP6377-378 PBD6658-659 54. (C) Monoclonal gammopathy of uneertain significance (MGUS) is charaCleri7.ed by the presence of an M protein "spike" in the absence of any associated disease of B cells. The diagnosis of MGUS is made when Ihe monoclonal spike is small (>3 g) and the palient has no Bence Jones proteinuria. MGUS may progress to multiple mye· loma in about 20% of patienls over 10 to 15 ye'drs. A plasmacyloma should appear on a bone sean. Waldenslrom macroglobulinemia should be aecompanied by an IgM spike. hepalOsplenomegaly. and Iymphadenopathy. Heavy chain disease is arare condilion Ihat may be seen with chronic Iymphocytic leukemia. In multiple myeloJlla, the spike is greater Ihan 3 g. <Ind usually the palient has bone lesions. BP6 381 PBD6 663-666 55. (O) This is a Reed-Stemberg cell, whieh is eharaCleristic for Hodgkin disease. Notiee also the nonneoplastie eosinophils. Iymphocyles. and macrophages in the back-

ground. Reed-Sternberg cells are the neoplastie component in Hodgkin disease, and unlike non-Hodgkin lymphomas, these transformed cells are scattered in a background of a proliferation of Ilonneoplastic inAammatory cells. As a historieal note, Ihe currenl Rye classifieation of Hodgkin disease grew out of an internalional conference held in Rye, Scotl<lnd. Nothing much happened al Ibe eonference. be~ cause everyone wanted lO play golf. Tbe meeting's organ+ izer reali7.ed thal lillle progress was being made, <Ind he assembled a few of his friends al Ibe bar in Ihe hotel the night before the eonference was lO end. After a few whis· kys, he gol them lO agree on a simple scheme wilb four eategories, and il has nol been revised in more than a quarter of a cenlury since-unlike Ihe many c1assification schemes for non-Hodgkin Iymphomas. BP6369-370 PBD6670-672 56. (B) The very high WBC count and lhe presence of peroxidase·posilive blasls (i.e.. myeloblasls) filling the mar· row are characterislic for acute myeloblastic leukemia. Tbis leukemia is most often seen in persons between the ages of 15 and 39 yeaes. CLL is characterized by the presence of small, malure Iymphocytes in peripheral blood and bone maITOW of older adults. Megakaryocytie leukemias are mee. CML is a1so seen in adults. but Ibis is a myeloproliferalive process with a range of myeloid differenliation. Most of Ihe myeloid cells are mature, and Ihere are relalively few blasts. ALL occurs in children <Ind young adulls. AZllrophi lie. peroxidase-posilive granules distingllish myeloblasls from Iymphoblasts. BP6374-376 PBDó 657 -677


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