Upper GI - UPDATED

Upper Gastrointestinal Pathology

Dr N Scott , Dr N Mapstone & Professor Neil A Shepherd Leeds Teaching Hospitals, Manchester Royal Infirmary & Gloucester & Cheltenham, UK

FRCPath Part 2 Surgical Course Gloucestershire Cellular Pathology Laboratory

About the exam • it is difficult (long, timed, lots to do) • it is not impossible • it is a general competency test • College wants you to pass, but only if they think you’re safe

• appropriate preparation: do exam practices • write quickly enough and keep calm • nine minutes per case – ensure timing…..

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About the exam

• a structured answer = a structured mind

• short summary of proffered data; nice description of the salient pathology; summary • each title: Information or Clinical Data, Histology, Summary underlined in red?

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You, the FRCPath exam and GI pathology • look at the information proffered – age, sex & clinical details • look at the slide – five seconds of holding up to the light • context • if the case is ‘easy’ – give extra information to demonstrate your knowledge, look for a second (or third or more) diagnosis!!

• if the case is difficult, give extra information to demonstrate how you would further investigate and what you would then do (second opinion, MDTM discussion, further clinical data, further biopsy, bigger (EMR/ER) biopsy, expert opinion)

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Case 1

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Clinical history 72F. Discrete erosion in upper oesophagus.

Oesophageal biopsies.

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Case 1: Diagnosis Gastric heterotopia (so-called ''inlet patch'')

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Marking scheme 3.5

3.0

Correct diagnosis with clinical correlation and relevance/prognosis

2.5

Good description, give differential diagnosis

2.0

Mediocre description, miss point of case (call it Barrett’s oesophagus, etc)

1.5

Don’t call it dysplasia (very unusual in gastric heterotopia)

1.0

Case 2

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Clinical history 18M. Oesophageal trachealisation.

Oesophageal biopsies.

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Case 2: Diagnosis ‘In keeping with eosinophilic oesophagitis’

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Marking scheme 3.5

3.0

Differential diagnosis. Comment on endoscopic findings. Knowledge of other tests

2.5

Suggest differential diagnosis.

2.0

Too dogmatic about diagnosis of EE….

1.5

Miss eosinophils.

1.0

Causes of intra-epithelial eosinophils in the oesophagus •

reflux (either acid or alkaline)

•

‘eosinophilic gastroenteritis’

•

‘eosinophilic oesophagitis’

•

drug/pill-induced oesophagitis

•

infections

•

achalasia

•

leiomyomatosis

•

inflammatory polyps including inflammatory fibroid polyp

•

tumours – secondary to obstructing tumours at OGJ

Kaye et al, 2007 •

eradication therapy (PDT, laser, ABC, etc) and neo-adjuvant chemoradiotherapy (especially in muscularis propria)

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Eosinophilic oesophagitis •

male patients with history of allergy/atopy

•

children or adults

•

chronic dysphagia in 63%, often since childhood - food sticking common

•

no evidence of GORD on pH monitoring

•

may be peripheral blood eosinophilia

•

responds to steroids, allergen exclusion, anti-IL5

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Eosinophilic oesophagitis

Endoscopic appearance of corrugated or ringed oesophagus (trachealisation)

Linear furrows (feline oesophagus) observed on endoscopy

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Case 3

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Clinical history 42M. Island of Barrett's epithelium within lower oesophagus.

Abnormal-appearing mucosa of gastro-oesophageal junction.

Mild duodenitis within bulb.

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Case 3: Diagnosis

Corroborative of Barrett’s oesophagus & CMV oesophagitis

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Marking scheme 3.5

3.0

Consider implications of CMV infection. Good description of difficulties of CLO vs OGJ mucosa

2.5

Suggest CMV. Competent interpretation of glandular appearances.

2.0

Miss CMV connection but describe abnormal cells.

1.5 1.0

Case 4

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Clinical history 70 year old male. Barrett's oesophagus.

EMR of oesophagus.

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Gloucestershire Cellular Pathology Laboratory

Case 3

Case 4: Diagnosis High grade dysplasia +/- intramucosal adenocarcinoma in CLO

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Marking scheme 3.5

3.0

Talk about management options. MDT discussion.

2.5

Good description. Correct diagnosis. Confirmed by second pathologist.

2.0

Incomplete description. Misgrade dysplasia.

1.5

Overcall as invasive adenocarcinoma.

1.0

Case 5

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Clinical history

55M. Oesophageal polyp.

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Gloucestershire Cellular Pathology Laboratory

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Case 5: Diagnosis

Granular cell tumour

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Marking scheme 3.5

3.0

Clinical significance. Remove with EMR. Majority benign and small.

Histogenesis and CD68 positive

2.5

Appropriate description and diagnosis

2.0

Miss diagnosis or lack conviction

1.5 1.0

Case 6

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Clinical history 50 year old female with EMR of oesophageal nodule.

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Gloucestershire Cellular Pathology Laboratory

Case 6: Diagnosis Smooth muscle tumour

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Marking scheme 3.5

3.0

Less likely to be GIST at this site. Emphasise unpredictable nature but this one small and circumscribed and likely to have a favourable natural history

2.5

Suggest correct diagnosis and nomenclature. Suitable corroborative tests.

2.0

Poor description; calling it leiomyoma………

1.5 1.0

Case 7

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Clinical history 53F. Nausea, vomiting and weight loss.

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Call it

Case 7: Diagnosis Chemical/reactive gastritis, now known as reactive gastropathy.

The presence of stainable iron indicates that this may be due to, at least in part, oral iron therapy.

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Marking scheme 3.5

3.0

Spot iron. Description of iron erosion disease in oesophagus, stomach and duodenum. History of ‘reactive gastropathy’.

2.5

Good description. Give causes of reactive gastropathy.

2.0

Describe and yet miss significance findings

1.5

Call it dysplasia……

1.0

Case 8

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Clinical history 77M. Microcytic anaemia.

Adenomatous pedunculated polyps in fundus. Gastritis anterior lower body. “Gastric fundal polyp“.

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Case 8: Diagnosis Xanthelasma or xanthoma of the stomach

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Marking scheme 3.5

3.0

Description of the possible cause

2.5

Description and additional tests.

2.0

Describe but no diagnosis

1.5 1.0

Call it signet ring cell carcinoma or other neoplasm…..

Case 9

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Clinical history 77F. Gastric antral biopsy.

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Case 9: Diagnosis

Gastric antral vascular ectasia (GAVE)

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Marking scheme 3.5

3.0

Full CPC discussion of GAVE.

2.5

Reactive gastropathy and suggest additional diagnosis.

2.0

Sound description only.

1.5

Call it dysplasia….

1.0

Case 10

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Clinical history 69M. Anaemia. Gastric polyp. Gastric biopsies.

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Gloucestershire Cellular Pathology Laboratory

Case 10: Diagnosis High grade lymphoma.

If you want to be really clever: DLBCL; centroblastic variant with an activated phenotype (WHO)

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Marking scheme 3.5

3.0

Good suggestions for immunophenotyping and molecular testing. Good description of types of primary gastric lymphoma and their management.

2.5

Lymphoma with reasonable adjunctive tests. Favour DLBCL.

2.0

Suggest differential diagnosis but lack direction.

1.5

Dogmatic wrong diagnosis (eg benign; carcinoma, etc).

1.0

Case 11

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Clinical history 48F. Wedge resection of gastric tumour.

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Case 11: Diagnosis Gastrointestinal stromal tumour (GIST), epithelioid type

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GIST Immunohistochemistry • c – kit ( CD117 ) • DOG – 1 • CD34 • SMA • Desmin • S100

Mutation Testing • c - kit mutation • PDGFR alpha • BRAF • SDH deficiency

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SDH deficient “Wild-Type” GISTs • • • • • • • • • • •

3 – 5 % of all GISTs Commoner in younger age groups ie. children and young adults < 30 May be part of Carneys Triad or CSS Located in Stomach Often multicentric, multinodular or plexiform Epithelioid or occasionally mixed morphology Metastatic to lymph nodes in 10 – 30 % cases Increased risk of distant metastasis Behaviour less easy to predict with AFIP /NIH consensus criteria Indolent behaviour with prolonged survival Less responsive to Imatinib

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Marking scheme 3.5

3.0

Consideration of molecular aspects and treatment.

2.5

Solid description. Sensible immunotesting. Good grasp of dataset content.

2.0

Basic description, wide differential diagnosis.

1.5

Dogmatic wrong tumour diagnosis

1.0

No diagnostic idea…..

INTERVAL

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Case 12

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Clinical history 28F. Strong family history of gastric cancer.

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Case 12: Diagnosis Signet ring cell adenocarcinoma

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Marking scheme 3.5

3.0

Discussion about familial gastric cancer, e-cadherin mutation/CDH1, genetic screening and prophylactic treatment.

2.5

Spot cells and suggest additional tests to confirm.

2.0

Spot cells. Unsure about diagnosis.

1.5 1.0

Xanthelasma/xanthoma ……

Case 13

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Clinical history 42M. OGD revealed mass with bleeding vessel in antrum.

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Gloucestershire Cellular Pathology Laboratory

Case 13: Diagnosis Glomus tumour

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Marking scheme 3.5 3.0

Correct diagnosis. Good immunophenotyping suggestions (ASMA, bcl-2, hcaldesmon but collagen IV best). Dissertation on glomus tumours in the gut.

2.5

Good differential diagnosis and supplementary immunotests. Should consider neuro-endocrine tumour which has a similar immunophenotype (synaptophysin positive).

2.0

Description only with poor differential diagnosis.

1.5

Dogmatic diagnosis of GIST (very different management).

1.0

Dogmatic diagnoses of tumours like adenocarcinoma.

Case 14

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Clinical history 19F. Normal upper GI tract at endoscopy.

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Case 14: Diagnosis Increased intra-epithelial lymphocytes: ‘Lymphocytic duodenosis’ ‘Intra-epithelial lymphocytosis with a normal villous architecture’

Gloucestershire Cellular Pathology Laboratory

Marking scheme 3.5

3.0

Give differential diagnosis and causes (lots). 25% have coeliac disease.

Correlate with serology and HLA phenotype.

2.5

Spot abnormality and possible significance.

2.0

Describe but no interpretation.

1.5

Call it normal…..

1.0

Case 15

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Clinical history

31F. Duodenal biopsies.

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Case 15: Diagnosis Giardiasis

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Marking scheme 3.5 3.0

95% of biopsies with giardiasis are otherwise entirely normal. Can see them in stomach and colon. Mention travel. Mention lots of plasma cells. Suggest other infections if immunosuppressed.

2.5

Description and spot organisms.

2.0 1.5 1.0

Miss giardia.

Case 16

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Clinical history

35F. Anaemia.

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Case 16: Diagnosis ‘In keeping with untreated coeliac disease’

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Marking scheme 3.5

3.0

Talk about Marsh type. Correlate with serology. HLA DQ2 and 8, etc

2.5

Good description. ‘Compatible with untreated coeliac disease’.

2.0

Over-confident (dogmatic coeliac disease).

1.5

Poor description and no summary.

1.0

Sero-Negative Villous Atrophy Infections: Giardia, Whipples Disease, Viral gastro-enteritis, Helicobacter, Bacterial Overgrowth, Tropical sprue, Atypical Mycobacteria Drugs : NSAIDs, Cytotoxic agents, Immune Checkpoint Inhibitors, Mycophenylate , Olmesartan etc.

Immune Deficiency & AutoImmune Disease : CVID , AIDs , Autoimmune Enteropathy Crohns Disease GvHD Collagenous Sprue Microvillus Inclusion Disease Radiation enteritis Eosinophilic Gastroenteritis Peptic Duodenitis

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VILLOUS ATROPHY – NOT ALL COELIAC DISEASE !!

• Things that should be there BUT aren’t … 

Plasma Cells

 Intra-epithelial Lymphocytes  Goblet Cells & Paneth Cells Gloucestershire Cellular Pathology Laboratory

VILLOUS ATROPHY – NOT ALL COELIAC DISEASE !!

• Things that are there BUT shouldn’t be …       

Giardia ( viral inclusions, cryptosporidium… ) Granulomas Apoptosis Crypt Abscesses Crypt distortion & Crypt loss Thickening of the subepithelial collagen plate Atypical cell populations …Foamy macrophages, Eosinophils etc.

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Case 17

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Clinical history 67M. Duodenitis and ? inflammatory polyps.

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Case 17: Diagnosis Gastric heterotopia.

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Marking scheme 3.5

3.0

‘Gastric heterotopia is the commonest cause of polypoid nodulation in the proximal duodenum’.

2.5

Describe well and suggest diagnosis

2.0

Suggest wrong diagnosis (eg gastric metaplasia) but recognise tissues.

1.5 1.0

Case 18

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Clinical history 46 year old male. 20 mm jejunal polyp.

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Gloucestershire Cellular Pathology Laboratory

Gloucestershire Cellular Pathology Laboratory

Case 18: Diagnosis Peutz-Jeghers polyp with Epithelial Misplacement.

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Marking scheme 3.5

3.0

Talk about PJ syndrome, AD, polyps & pigment: cancer risk

2.5

Good description with good differential diagnosis. Suggest correct diagnosis.

2.0

Description only.

1.5

Wrong diagnosis such as adenoma.

1.0

Mistaking epithelial misplacement for adenocarcinoma.

Case 19

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Clinical history 64M. Duodenal adenocarcinoma. Whipple’s resection.

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Case 19: Diagnosis Seminoma

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Marking scheme 3.5

3.0

Suggest correct diagnosis and likely secondary.

2.5

Good description with reasonable differential diagnosis and further tests.

2.0

Lacks direction and logical approach.

1.5

Benign primary tumour.

1.0

Case 20

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Clinical history 65M. Pancreatic mass. Whipple’s resection.

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Case 20: Diagnosis Clear cell carcinoma, consistent with metastasis from a primary renal (clear) cell carcinoma.

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Marking scheme 3.5

3.0

Ask about history, imaging, etc.

2.5

Good approach with good differential diagnosis.

2.0

Differential diagnosis with less confidence.

1.5 1.0

Benign diagnosis, perhaps primary tumour.

Case 21.

CLINICAL HISTORY 76 year old male – lesion in fundus of stomach.

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Gloucestershire Cellular Pathology Laboratory

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Case 21 . Diagnosis Kaposi Sarcoma – HIV positive.

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Case 22.

64 year old female – persistent gastric ulcer despite PPI.

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Gloucestershire Cellular Pathology Laboratory

Case 22 Diagnosis Erosive Gastritis with reactive epithelial atypia

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Reactive Atypia versus Epithelial Dysplasia • Context : Acute inflammation and Ulceration • Degree of cytological & architectural atypia ie. range of nuclear size, pleomorphism, nucleoli, atypical mitotic figures • “monotonous” or “monomorphic” atypia versus “pleomorphic” atypia ( are all cells atypical in the same way ? ) • Maturation towards mucosal surface ( but remember “basal crypt dysplasia” ) • Spectrum of atypia ie. abrupt transition from atypical to reactive or normal epithelium versus gradual merging of atypical cells with reactive epithelium at edges • Immunohistochemistry : p53, ki67 etc.

• Second Opinion & “indefinite for dysplasia” ( re-biopsy ) Gloucestershire Cellular Pathology Laboratory

Case 23 57 year old female – thickened gastric wall – gastric biopsy.

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Gloucestershire Cellular Pathology Laboratory

Gloucestershire Cellular Pathology Laboratory

Case 23 Diagnosis Metastatic Lobular Carcinoma of Breast ( ER positive )

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Any comments or questions?

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