Case 2 -

Peripheral T-NHL, Unspecified with B-cell Proliferation and RS-like Cells of B-cell Phenotype Associated with EBV Leticia Quintanilla-Martinez Ingolstaedter Landstraße 1 Oberschleissheim, Germany

Case History: Cervical lymph node in a 52-year-old male patient. The bone marrow was free of disease. The patient received CHOP and achieved remission. The lymph node showed partial effacement of the architecture with some reactive B-cell areas recognizable. In other areas there were aggregates of atypical clear cells intermingled with reactive B-cell areas, and sheets of large centroblasts. Scattered throughout the lymph node, Reed-Sternberg (RS)-like cells were identified. The clear cells were CD3+CD4+BetaF1+CD5+ and CD8 and CD10 were negative. The RS-like cells were CD30+, CD20+/-, CD15- and EBV LMP1+. Some FDC networks were recognized. Two years later the patient developed cervical adenopathy that was diagnosed histologically as atypical lymphadenopathy, after extensive ancillary studies. Case 2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Peripheral T-NHL, unspecified with B-cell proliferation and RS-like cells of B-cell phenotype associated with EBV. Molecular analysis demonstrated monoclonal rearrangements of both TCRγ and IgH genes. Discussion: Peripheral T-cell lymphoma (PTCL), unspecified accounts for approximately 50% of the peripheral T-cell lymphomas in Western countries. This group encompasses mostly nodal cases that do not belong to any of the better-defined entities. The cytological spectrum is extremely broad, but most cases show medium to large-size cells with irregular, pleomorphic nuclei. Clear cells, RS-like cells, increased high endothelial vessels and clusters of epithelioid histiocytes are often present. Recently, attention has been given to a group of PTCL cases complicated by a proliferation of large B-cells, sometimes with Reed-Sternberg-like cell morphology (Higgins). In most cases, the transformed B cells are positive for EBV-LMP1, suggesting an EBV-driven B-cell lymphoproliferation. (Zettl) The amount of large cells varies but most authors require >25% of the background cells to be large B-cells to make this diagnosis. These B-cells may show polyclonal, oligoclonal or monoclonal IgH gene rearrangements. The finding of large B-cells intermingled with a proliferation of T-cells may result in a misdiagnosis of a reactive process like infectious mononucleosis, or neoplasms like T-cell rich B-cell lymphoma, Hodgkin´s lymphoma and most important angioimmunoblastic T-cell lymphoma (AILT). The present case represents an example of PTCL, unspecified complicated by a large B-cell proliferation with borderline morphology to AILT (Quintanilla-Martinez). A recent study analyzed the usefulness of CD10 expression in the differential diagnosis between PTCL complicated with large B-cells and AILT (Reichard). Only 20% of the PTCL were CD10 positive whereas 90% of the AILT cases were CD10 positive. Accordingly, in this case the neoplastic T-cells were CD10 negative. Furthermore, in a recent study by Dupuis et al, they demonstrated that CXCL13 was positive in 100% of the cases of AILT, whereas only 30% of the PTCL cases were CXCL13 positive. Clinically, EBV-associated B-cell lymphoproliferation occurring in AILT does not seem to be associated with a more aggressive clinical course, whereas PTCL, nos in general, have a bad prognosis, respond poorly to therapy and have short survival with no sustained remission. The differential diagnosis in these cases is often difficult and sometimes requires extensive immunophenotypic and molecular analysis. References: Higgins JP, van de Rijn M, Jones CD, et al. Peripheral T-cell lymphoma complicated by a proliferation of large B-cells. Am J Clin Pathol 2000; 114:236-47. Zettl A, Lee S-S, Rüdiger T, et al. EBV associated B-cell lymphoproliferative disorders in AILT and peripheral T-cell lymphoma, unspecified. Am J Clin Pathol 2002; 117:368-79. 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 Reichard KK, Schwartz EJ, Higgins JP, et al. CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells. Mod Pathol 2006; 19:337-343 Dupuis J, Boye K, Martin N, et al. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol 2006; 30:490-494