Contributed by Pranav Patwardhan, MD and Sara Monaghan, MD
Contributed by Pranav Patwardhan, MD and Sara Monaghan, MD
CLINICAL HISTORY
A man in his late 60s presented with low appetite and early satiety symptoms since 2-3 weeks. Weight loss of more than 20kg was also noted in the past year. The patient also had a worsening generalized pruritis and diffuse body rash for 4-6 months. He was initially treated for scabies but the pruritis and rash did not resolve. Axillary, subcarinal, mediastinal, retroperitoneal, pelvic and inguinal lymphadenopathy was found on CT imaging. The largest node was left axillary lymph node which measured 1.7 cm while rest of the abdominal and the mediastinal lymph nodes had a maximum diameter of 1.2-1.3 cm. Due to the lymphadenopathy, constitutional symptoms, significant weight loss and history of rash, lymphoma was the major consideration. The patient's past medical history was significant for chronic kidney disease, COPD and hypertension. A diagnosis of MGUS was made 3 years ago but the bone marrow was not involved by a plasma cell neoplasm. The abnormal protein detected on serum protein electrophoresis (SPEP) was 0.3 g/dl at that time and immunofixation revealed IgG Kappa monoclonal gammopathy and monoclonal free lambda light chain. The free kappa to lambda light chain ratio was 0.89.
LABORATORY WORKUP
Complete blood count showed mild leukopenia (2.8 X 109 /L)with absolute neutropenia (1.7 X 109/L) and absolute lymphopenia (0.2 X 109/L) and thrombocytopenia (103 X 109/L). Electrolyte and chemistry workup demonstrated moderate hypercalcemia (12.3 mg/dl), hyperuricemia and mildly elevated LDH (245 IU/L).
Flow cytometry analysis demonstrated an abnormal T cell population, accounting for about 24% of total events. The abnormal T cell subset was positive for CD2, CD3, CD4, CD5 (bright) and negative for CD7, CD8 and CD56. The cells showed expression of TCR αβ, heterogeneous expression of CD25, were partial positive for CD16/CD57 and a few were possibly positive for CD10.
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On histopathological examination, the lymph node architecture was largely effaced by a heterogenous proliferation. Distinct larger atypical cells were found with irregular nuclear contours, somewhat vesicular chromatin and occasional prominent nucleoli. The background demonstrated smaller lymphocytes, mildly increased eosinophils and occasional plasma cells. Also seen were prominent high endothelial venules. Immunohistochemical evaluation for CD3 highlighted the larger, more abnormal cells, supporting they were part of the neoplastic proliferation. The abnormal cells were also highlighted by T follicular helper cell markers ICOS, PD1 and BCL6. The abnormal population also strongly expressed CD57. A few CD20 positive B-cell rich areas were noted. CD21 highlighted somewhat expanded and irregular dendritic cell meshworks in the B-cell areas and also around the high endothelial venules. EBER-in situ hybridization highlighted rare cells.
H&E stained slides demonstrate effaced lymph node architecture, high endothelial venules and neoplastic cell population which is larger in size and shows irregular nuclear membrane, vesicular nucleus.
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Overall, the histomorphological features, the clinical history of rash and the flow cytometry/ immunohistochemical findings strongly supported the diagnosis and further classification as angioimmunoblastic T-cell lymphoma. PCR on paraffin-embedded tissue in our case demonstrated TCR clonality, helping to further confirm the neoplastic nature of the abnormal T cell proliferation. Adult T-cell leukemia/ lymphoma (ATLL) was also considered as an alternative possibility due to the CD25 expression among the CD4 positive T cells detected by flow cytometry, but this was felt to be less likely because the pathologic and clinical findings were so typical for AITL. A subsequent serologic study was negative for HTLV-1, which helped to further exclude ATLL.
