Secondary B-cell Lymphoma Associated with the Epstein-Barr Virus in Chronic Lymphocytic Leukemia Patients

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, value >0.05), longer interval between CLL and RT diagnosis (median 4.2 vs. 2.9 years, value >0.05), and shorter overall survival (median 4 vs. 10 months, 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.