Clinical characteristics and outcomes in Epstein-Barr virus-positive diffuse large B-cell lymphoma: a multicenter retrospective study.

Background/aim: Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), is a rare and aggressive subtype of B-cell lymphoma, recognized as a distinct entity in the revised fourth edition of the 2016 World Health Organization (WHO) classification. This retrospective study aims to evaluate the prevalence, clinical and histopathological characteristics, and survival outcomes of patients diagnosed with EBV+ DLBCL-NOS. Materials and methods: This retrospective study included 92 newly diagnosed DLBCL patients treated at two centers between 2016 and 2024. EBV status was determined by in situ hybridization for EBER, with positivity defined as ≥ 50% nuclear staining in tumor cells. Results: Among 92 patients, 81 (88.1%) were EBV-negative and 11 (11.9%) were EBV-positive. The median age was 63 years. EBV-positive patients had significantly more advanced-stage disease (100% versus 71.6%, p = 0.049), higher rates of splenic involvement (72.7% versus 38.3%, p = 0.048), elevated LDH levels (median: 773 U/L versus 326 U/L, p = 0.043), and a higher proportion with high-risk IPI scores (IPI ≥ 4: 63.6% versus 27.2%, p = 0.032). No significant differences were observed in age, sex, bulky disease, extranodal involvement, or molecular subtype. Median PFS was 12 months in the EBV-positive group, whereas it was not reached in the EBV-negative group (p = 0.005). EBV positivity was identified as an independent risk factor for inferior PFS (HR: 6.256, 95% CI: 2.398-16.324, p < 0.001), but not for overall survival (OS). Patients with ECOG performance status ≥ 2 and bone marrow involvement also had significantly worse PFS and OS. Conclusion: EBV+ DLBCL is characterized by distinct clinical features, including advanced-stage disease and poorer PFS. Variability in reported prevalence highlights the need for standardized diagnostic criteria. Further research is essential to develop tailored therapeutic strategies and improve outcomes for this rare lymphoma subtype.