EBV-associated histological transformation of marginal zone lymphomas: two case reports and a literature review

Marginal zone lymphoma (MZL) undergoes histological transformation (HT) in approximately 5%–10% of patients during the clinical course of the disease. Here, we report two cases of Epstein–Barr virus (EBV)–associated HT in MZL and review the relevant literature. The first case describes a non-immunocompromised woman with splenic MZL that transformed into EBV-positive diffuse large B-cell lymphoma (DLBCL). EBV-positive cells were observed sparsely in the initial MZL. Although the patient was treated with multi-agent chemotherapy, she died only 3 months after the HT diagnosis. The second case describes a woman with nodal MZL that transformed into EBV-positive DLBCL; this woman had a history of rheumatoid arthritis and methotrexate use. No EBV-positive cells were observed in the initial MZL. She received chemotherapy and has remained in complete remission for 14 months since the HT diagnosis. Polymerase chain reaction–based clonality analysis of IGH and target panel sequencing confirmed the clonal relationship between MZL and DLBCL in both cases. We also discuss the clinicopathological features of EBV-associated HT, focusing on EBV-positive cells in MZL, history of treatment, immune status before HT, clinical course, and genetic abnormalities. Transformation associated with EBV occurs regardless of immunodeficiency or the initial presence of EBV-positive cells in MZL, and the prognosis varies from case to case.