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Case report from ASH Lymphadenopathy. Dr. Tariq Roshan


History

 A 60 year-old man complains of a new lump in the right groin for the past six weeks.  What are the major pathophysiologic mechanisms for lymph node enlargement?  Is the lymph node tender.  Have you felt swollen lymph nodes in this or another area befo  Do you have fever or drenching sweats or loss of more then 10


History  Have you traveled to foreign countries?  Have you had any of the following:     

change in bowel movements pain in the abdomen blood in the stools or black tarry stools fullness in the stomach inability to eat a full meal (early satiety)?

 Have you ever: Abused intravenous drugs?  Shared needles with other people?  Had anal receptive sexual intercourse?  Had heterosexual intercourse with multiple partners?

 Did you receive blood or blood product transfusions prior to 1985?


History  Have you noticed unusual bleeding, easy bruising or red spots in the skin?  Have you noticed any sores on your penis or abnormal discharge from your penis?  Do you have any pain, redness, or swelling in your leg?  No I have not noticed any pain, redness, or swelling in my leg.  Cellulitis can cause inguinal adenopathy.


Pathophysiolgy.  A lymph node may enlarge in response to an infection, a non-specific inflammatory reaction, or a malignant growth of its cells.


Is the lymph node tender.  The node is not painful  Lymph nodes that become enlarged as a result of infection are usually tender to touch, whereas malignant lymph nodes do not hurt. In addition, infectious nodes can be erythematous and warm.


Have you felt swollen lymph nodes in th  Yes, I have noted other enlarged nodes, but my groin area concerns me the most.  Infections most often cause localized lymphadenopathy. Disseminated lymphadenopathy is more likely due to a malignancy but can be due to  HIV  EBV.

 Malignant lymphadenopathy can also wax and wane, sometimes for months before a final diagnosis is made.


Do you have fever or drenching sweats  No, I have not had fevers, or sweats. However, I have lost 8 pounds over the past 6 months.  One or more of these symptoms is present in many patients with lymphoma. The classic “B” symptoms of lymphoma are – Temperature greater than 380C, – Drenching night sweats – Unintentional loss or 10% of body weight over 6 months.


Have you traveled to foreign countries?  I have lived in Texas all my life, and have not recently traveled outside Texas.  This is an important question in order to rule out infectious etiologies which might be acquired in other countries.  Some of these may cause disseminated lymphadenopathy or signs that might be mistaken for a malignancy.  Tuberculosis.  Histoplasmosis.


 I have none of these problems. – The gasterointestinal tract is a very common site of primary extranodal lymphoma presentation. It can also be a place of spread of lymphoma. In addition, enlarged spleen can give left upper quadrant pain or early satiety.

 The patient reported none of these risk factors for HIV – HIV may cause disseminated lymphadenopathy. In addition people with HIV infection have a 300 fold increased risk of developing high-grade NHL.


 No I don’t have a problem with any of that.  Spontaneous bleeding can ocure if the platelet count is < 10,000/ cub. mm, either due to consumption or due to underproduction from a bone marrow that is replaced by a malignant process.

 I have none of these symptoms.  Squamous cell carcinoma of the penis can cause inguinal adenopathy.  Venereal diseases including syphilis, chancroid, genital herpes, and lymphogranuloma venereum, can also cause inguinal adenopathy.


Physical Exam  A 60 year-old man complains of a new lump in the right groin for the past six weeks.  What should you look for on his physical exam that would help you to narrow the differential diagnosis? Name several lymph node areas that you should examine.  Cervical, supraclavicular, axillary, epitrochlear, and inguinal.  Be sure to examine the tonsils and spleen as well, as these are also lymphoid tissues


Physical Examination  General: Well nourished man in no acute distress.  HEENT: Pale mucosa, no scleral icterus, no orpharyngeal lesions, no tonsillar enlargement.  Lungs - Clear to auscultation and rhythm.  Heart - Regular rate without murmur.  Abdomen - spleen enlarged to 6 cm below the costal margin, firm and non tender to palpation. The liver is enlarged.  Musculoskeletal - Normal.  Genitourinary - Normal male genitals without lesions on the penis or in the perirectal area.  Neurological - normal.  Lymphatics - generalized adenopathy. The nodes range from 1.5 cm to 4 cm in diameter, are rubbery and not tender to palpation.  Skin - normal.  What do you think now?  Generalized rubbery adenopathy and significant splenomegaly. These findings point to a systemic disease rather than a localized infection.


Differential diagnosis at this point Differential Diagnosis The following diagnoses should be considered at this point.

          

Differential diagnosis of generalized adenopathy: Reactive hyperplasia due to HIV Secondary syphilis Epstein-Barr virus (mononucleosis) Tuberculosis Lymphoma Cytomegalovirus Brucillosis Toxoplasmosis Sarcoidosis Differential diagnosis of localized inguinal adenopathy: Cat-scratch fever (bartonella) Herpes simplex type II


What lab studies should be requested?  CBC, peripheral blood smear & platelet count – – – –

WBC 2000/ml Hemoglobin 8.3 g/dl Platelets 80,000 /ml The peripheral smear does not show abnormal lymphoid cells.

– A low hemoglobin could due to marrow replacement with lymphoma, or to iron deficiency anemia secondary to blood loss through the gastrointestinal tract. – Platelets could drop due to:  splenic sequestration by the enlarged spleen  ITP (which can be associated with lymphomas)  lack of production due to extensive marrow infiltration by lymphoma a combination of the above.

 There will be evidence of peripheral blood involvement by lymphoma in some patients.


Lab studies  Serum chemistries – Normal.  Liver and renal chemistries will be abnormal if these organs are involved or obstructed by lymphoma. Spontaneous tumor lysis syndrome, (elevated serum potassium, phosphate, and uric acid, and low serum calcium) is almost never present at presentation of lymphoma, but can happen with therapy if the lymphoma is rapidly proliferating or presenting with bulky disease or with a leukemic picture.

 LDH 250 (0-190)  B2 microglobin 1.5ng/ml(0-2.5 ng/ml)  Pretreatment serum levels of LDH and ß2 microglobulin are elevated in many patients with lymphoma. In general, a higher LDH value correlates with a higher proliferative rate.


Lab studies  Hemoccult testing of stool – Negative  Hemoccult testing of the stool is important as some patients with lymphoma will have GI involvement at diagnosis.


Radiograph.  What radiographic procedures would you recommend? – CT scan chest, abdomen, and pelvis with administration of both oral and intravenous contrast. – The abdominal CT scans in this patient show diffuse involvement of the retroperitoneal nodes.


Laboratory Studies and Procedures  Diagnostic Procedures: What diagnostic procedure(s) should be done? – Diagnostic Procedures – Lymph node biopsy  Should this be a:  Fine needle aspirate?  Core needle biopsy?  Excisional biopsy?

– Bone marrow aspirate and biopsy  Why does the patient need both an aspirate & biopsy of the bone marrow?


ď&#x201A;§ In patients with accessible peripheral lymph nodes, an excisional biopsy (surgical removal of the entire lymph node) is strongly preferred over a fine needle aspirate or a core needle biopsy. An excisional biopsy provides more tissue for evaluation and permits the hematopathologist to evaluate the architecture of the lymph node. A fine needle aspirate (although useful in the evaluation of thyroid nodules and breast cysts) is not adequate for the evaluation of possible lymphoma.


ď&#x201A;§ The aspirate and biopsy provide complementary information. The aspirate shows the morphology (appearance) of the cells in the marrow in detail, and can be sent for flow cytometry. The biopsy shows the cellularity of the marrow (proportion of the marrow space occupied by cells), and can look for replacement of the marrow with fibrosis, tumor cells, or granuloma.


List of studies that you should request on the lymph node. – Histopathology  Findings for this patient

– Flow Cytometry  Findings for this patient

– Molecular Studies  Findings for this patient

– Culture  Findings for this patient


Histopathology ď&#x201A;§ To evaluate the size and appearance of the lymphoid cells, and whether these cells involve the node in a nodular (follicular) or diffuse pattern. ď&#x201A;§ May also proceed with immunocytochemistry. This means staining the lymph node with monoclonal antibodies specific for B or T lymphocytes, followed by a second antibody tagged with a visible label such as horseradish peroxidase.


Flow Cytometry ď&#x201A;§ The laboratory reports the following characteristics for this patient Coexpression of CD5-CD19, negative CD23, positive FMC-7


Molecular Studies ď&#x201A;§ Depending on the results of the initial histopathology and flow cytometry data, these studies may include an evaluation for immunoglobulin gene rearrangement (a characteristic of B cell lymphomas), T cell receptor rearrangement (a characteristic of T-cell lymphomas), or specific oncogenes associated with certain lymphoma subtypes. ď&#x201A;§ The laboratory reports the following characteristics for this patient Cytogenetics shows a translocation t(11;14)(q13;q32). The fluorescent in situ hybridization technique (FISH) also detects the cyclin D1 translocation.


Culture ď&#x201A;§ If an infectious cause of adenopathy is in the differential diagnosis, the node can be sent to the microbiology laboratory for culture. ď&#x201A;§ The lab reports no infectious process present.


Bone marrow aspirate.


Diagnosis. The findings lead to the diagnosis of

Mantle cell lymphoma.


Mantle Cell Lymphoma.  The definite diagnosis.  Histopathologic.  Necessary to diffrentiate between Mantle zone pattern, follicular and diffuse variants.

 Phenotypically  CD 20 and CD 5 co-expression.  CD 23 negative and FMC-7 positive.  CD 10 negative.

 Important D/D  Small lymphocytic lymphoma,  Follicular small cleaved cell lymphoma  Lymphoblastic lymphoma.


Case report from ash