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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12308-016-0273-8) contains supplementary material, which is available to authorized users.
Highlights
Up to 10 % of patients with B-cell chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, eventually develop an aggressive secondary lymphoma referred to as Richter transformation (RT) [1]
Rossi et al suggested that Epstein-Barr virus (EBV)-positive lymphoma in the context of CLL represents a novel type of immunodeficiency-related lymphoma that may develop following T-cell depletion or chemotherapy [9]
Following an intriguing case of EBV-related large B-cell transformation in the brain of a CLL patient, we reviewed all cases of secondary B-cell lymphoma in CLL patients available in our archive
Summary
Up to 10 % of patients with B-cell chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, eventually develop an aggressive secondary lymphoma (most commonly diffuse large B-cell lymphoma, DLBCL) referred to as Richter transformation (RT) [1] Currently both clonally related and clonally unrelated secondary lymphomas. J Hematopathol (2016) 9:113–120 are referred to as RT, recent (epi)genetic studies have demonstrated that these are distinct entities [2, 3] This is apparent from the clinical setting as Btrue,^ i.e., clonally related cases of RT have a dismal prognosis compared to clonally unrelated DLBCL, which follows a disease course similar to de novo DLBCL [4]. We encourage monitoring of EBV titers in newly diagnosed CLL and systematic screening for EBV in RT, in elderly patients, to validate this hypothesis in a larger series of patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
