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

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Abstract
Background/aimEpstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), represents a rare and aggressive subtype of B-cell lymphoma, officially classified as a distinct entity in the revised 4th edition of the World Health Organization (WHO) 2016 classification. This retrospective study aims to evaluate the prevalence, clinical characteristics, histopathological characteristics, and survival results of patients diagnosed with EBV+ DLBCL-NOS.Materials and methodsOur retrospective study included 92 newly diagnosed DLBCL patients treated at two centers between 2016 and 2024. EBV status was determined using in situ hybridization for EBER, with positivity defined as; ≥50% nuclear staining in tumor cells. ResultsAmong 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% vs. 71.6%, p=0.049), higher rates of splenic involvement (72.7% vs. 38.3%, p=0.048), elevated LDH levels (median 773 U/L vs. 326 U/L, p=0.043), and a greater proportion with high-risk IPI scores (IPI≥4: 63.6% vs. 27.2%, p=0.032). No differences were observed in age, gender, bulky disease, extranodal involvement, or molecular subtype. Median PFS was 12 months in the EBV-positive group, while 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 overall survival (OS). Patients with ECOG performance status ≥2 and bone marrow involvement also had significantly worse PFS and OS. ConclusionEBV+ DLBCL is characterized by distinct clinical features, including advanced-stage disease and poorer PFS. Variability in reported prevalence underscores the need for standardized diagnostic criteria. Further research is critical to develop tailored targeted therapeutic strategies and improve outcomes for this rare lymphoma subtype.

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