Case 3 -

AILT Classic Type Leticia Quintanilla-Martinez Ingolstaedter Landstraße 1 Oberschleissheim, Germany

Case History: Cervical lymph node in a 79-year-old female patient. The patient had generalized lymphadenopathy and general symptoms. The lymph node showed complete effacement of the architecture by a polymorphic infiltrate of lymphocytes, transformed large lymphoid blasts, Reed-Sternberg (RS)-like cells, plasma cells and abundant epithelioid histiocytes within a prominent vascular network of arborizing high-endothelial vessels. Perivascular collections of atypical medium-large-sized lymphoid cells with clear cytoplasm were observed. The neoplastic cells were CD5+CD3+CD4+. CD20 highlighted many large transformed blasts and RS-like cells that were CD30+ and LMP1+. The proliferation of follicular dendritic cells (FDC) was demonstrated with CD23 and CD35. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: AILT classic type. Molecular analysis: TCRγ monoclonal and IgH polyclonal. Discussion: Angioimmunoblastic T-cell lymphoma (AILT) represents 15% to 30% of peripheral T-cell lymphomas (PTCL´s). AILT is a systemic disorder most frequent in middle-aged and elderly patients with a peak incidence in the 6th and 7th decade of life. It is characterized by generalized lymphadenopathy, hepatosplenomegaly, constitutional symptoms, skin rash, anemia, and polyclonal hyperglobulinemia. The diagnosis is often difficult, relying mostly on strict morphologic and molecular criteria. This case has all the morphologic features of AILT (mentioned above), however the abundant epithelioid cell reaction and the presence of transformed large B-cells, some with RS-like features may complicate the diagnosis due to the overlapping histological features with a variety of reactive and neoplastic conditions such as atypical T-zone hyperplasia (paracortical hyperplasia), PTCL, nos, diffuse large B-cell lymphoma and Hodgkin´s lymphoma. Some cases of AILT may show a prominent admixture of epithelioid cells, like in this case, obscuring the diagnostic morphologic features of the disease. The diagnosis of AILT relies mostly on the presence of arborizing vessels and proliferating FDC, in contrast to epithelioid-cell rich Hodgkin lymphoma (containing classical RS cells) and epithelioid-cell rich PTCL, unspecified (Lennert´s lymphoma), where these features are lacking (Patsouris). The transformed large B-cell blasts are a frequent finding in AILT. In most of the cases, it is triggered by EBV infection. These cells may be diffusely scattered or form confluent sheets indistinguishable from diffuse large B-cell lymphomas (Zettl). In addition, there is clear evidence that large B-cell lymphomas may arise in AILT. These large B-cell lymphomas may be present at the initial diagnosis or develop over time. (Abruzzo) The B-cell blasts are usually EBER+, CD20+, CD30+, CD15- and LMP1+/-, as was in the present case. Rare cases show the presence of typical RS cells with a classic phenotype (CD20+/-), CD30+, CD15+, EBV+) in an otherwise typical setting of AILT (Quintanilla-Martinez). In contrast to HL, molecular studies reveal clonal rearrangement of the TCRγ chain gene, in addition to the oligoclonal pattern of IgH chain gene in microdissected RS-like cells. Recently, it has been shown that the neoplastic cells in a high proportion of AILT cases (80-90%) express CD10 (Attygale), a marker that is not express in other T-cell lymphomas with the exception of rare PTCL, nos. Although further studies have confirmed this observation, the expression of CD10 in AILT is often weak, heterogeneous and confined to a small population of tumor cells, mostly the clear cell population and the neoplastic cells around the residual follicles (Dupuis). More recently, Grogg et al reported strong expression of CXCL13 (a chemokine up-regulated in the germinal center T helper cell subset), by the vast majority of the tumor cells (>80%) and in most cases of AILT (86%). The expression of CD10, BCL6 and CXCL13, in addition to being an excellent combination for the diagnosis of AILT, provides another piece of evidence that AILT might derive from follicular helper T-cells. References: Patsouris E, Noel H, Lennert K. AILT with a high content of epithelioid cells. Histopathology and comparison with lymphoepithelioid cell lymphoma. Am J Surg Path 1989; 13:262-275 Zettl AS, Lee S-S, Rüdiger T, et al. Epstein-Barr virus associated B-cell lymphoproliferative disorders in AILT and PTCL, unspecified. Am J Clin Pathol 2002; 117: 368-369 Quintanilla-Martinez L, Fend F, et al. Peripheral T-cell lymphoma with RS like cells of B-cell phenotype associated with EBV infection. Am J Surg Pathol 1999; 23:1233-1240 Attygale A, et al. Neoplastic T cells in AILT express CD10. Blood 2002; 99:627-633 Grogg KL, et al. AILT: a neoplasm of germinal-center T-helper cell? Blood 2005; 106:1501-1502 Dupuis J, et al. Expression of CXCL13 by neoplastic cells in AITL. A new diagnostic marker providing evidence that AILT derives from follicular helper T-cells. Am J Surg Pathol 2006;30:490-94