EBV+ polymorphic B-cell lymphoproliferative disorder, NOS: a single-center study of a newly recognized pathologic entity

EBV-positive polymorphic B-cell lymphoproliferative disorder, NOS (poly B-LPD), is a newly defined entity in the 2022 International Consensus Classification of mature lymphoid neoplasms. Its clinical behavior and optimal treatment approach remain poorly characterized. We conducted a retrospective study of 31 patients diagnosed with EBV+ poly B-LPD at Mayo Clinic (2003-2024), excluding transplant recipients. Median age was 56 years; 71% had extranodal involvement, 68% presented with stage III/IV disease, and 52% had autoimmune conditions. Thirty-five percent (n = 11) were on immunosuppressive therapy at diagnosis, all of whom underwent reduction of immunosuppression (RIS); five underwent RIS alone, achieving four complete responses including two with central nervous system (CNS) involvement. Rituximab was effective in patients with or without prior immunosuppression. Histologic transformation to diffuse large B-cell lymphoma (DLBCL) or emergence of T-cell lymphomas occurred in immunochemotherapy non-responders or at relapse, emphasizing the role of re-biopsy in this subset of patients. At a median follow-up of 6 years, median event-free (EFS) and overall survival (OS) were 8.5 and 8.7 years, respectively. EFS was not significantly influenced by increasing IPI scores (p = 0.09), CNS involvement (p = 0.5), or immunosuppression at diagnosis (p = 0.2). There was a trend towards improved OS in patients who were on immunosuppressive therapy at diagnosis, however, this was not statistically significant, p = 0.054. This is the first study to characterize EBV+ poly B-LPD within the ICC 2022 framework. Larger studies are needed to validate these findings, define prognostic markers and guide therapy.