Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients

Julie Morscio; Emilie Bittoun; Nathalie Volders; Eveline Lurquin; Iwona Wlodarska; Olivier Gheysens; Peter Vandenberghe; Gregor Verhoef; Philippe Demaerel; Daan Dierickx; Xavier Sagaert; Ann Janssens; Thomas Tousseyn

doi:10.1007/s12308-016-0273-8

Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients

J Hematop. 2016 May 21:9:113-120. doi: 10.1007/s12308-016-0273-8. eCollection 2016.

Authors

Affiliations

¹ 1Department of Imaging and Pathology, Lab for Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.
² 2Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
³ 3Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
⁴ 4Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium.
⁵ 5Hematology Department, University Hospitals Leuven, Leuven, Belgium.
⁶ 6Department of Radiology, University Hospitals Leuven, Leuven, Belgium.

Abstract

Up to 10 % of chronic lymphocytic leukemia (CLL) patients present with aggressive secondary B-cell lymphoma (most frequently diffuse large B-cell lymphoma, DLBCL) which may be clonally related to the CLL (i.e., Richter transformation, RT, 80 % of the cases) or de novo (20 % of the cases). Several genetic lesions associated with RT have already been identified, but the potential role of the Epstein-Barr virus (EBV) has been largely overlooked. In this study, we describe six CLL patients who developed a secondary EBV-positive (EBV⁺) B-cell lymphoma (five DLBCL, one Hodgkin lymphoma) and compare their clinicopathological characteristics to ten CLL patients with EBV-negative (EBV^-) secondary B-cell lymphomas (all DLBCL). All 16 patients had a history of iatrogenic immunosuppression or chemotherapy. Eighty percent had received fludarabine as part of the CLL treatment. Most secondary lymphomas were clonally related to the previous CLL (3/4 EBV⁺, 7/7 EBV^- cases tested). Notably EBV⁺ RT was associated with a trend for older age at onset (median 72 vs. 63 years, p value >0.05), longer interval between CLL and RT diagnosis (median 4.2 vs. 2.9 years, p value >0.05), and shorter overall survival (median 4 vs. 10 months, p value >0.05). These differences were not significant, probably due to small sample size. Immunohistochemical profiling suggested more frequent overexpression of TP53 and MYC in EBV^- compared to EBV⁺ secondary lymphoma. Based on this small retrospective single center series, we hypothesize that EBV⁺ RT may constitute a separate subgroup of RT. Larger series are required to validate this suggestion.

Keywords: Chronic lymphocytic leukemia; Epstein-Barr virus; Immunodeficiency-related lymphoma; Immunomodulatory agent-related lymphoproliferation; Immunosuppression-related lymphoproliferation; Richter transformation.