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.