Pearls and Pitfalls in Lymph Node Diagnosis
Case 2 -
Peripheral T-NHL, Unspecified with B-cell Proliferation and RS-like Cells of B-cell Phenotype Associated with EBV
Ingolstaedter Landstraße 1
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
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.
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
The differential diagnosis in these cases is often difficult and sometimes requires extensive
immunophenotypic and molecular analysis.
- 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