Dismal Outcome of EBV-Positive Nodal T/NK-Cell Lymphoma: A Multicenter Retrospective Study.

[BACKGROUND] Epstein-Barr virus (EBV)-positive nodal T- and natural killer (NK)-cell lymphoma (EB-nTNKL) is a newly defined, rare, and aggressive EBV-driven lymphoid malignancy that typically affects older individuals, predominantly male, of East Asian descent. It is characterized by a cytotoxic T-cell phenotype, with only a limited number of cases documented to date.

[METHODS] We performed a multicenter retrospective analysis of 11 patients diagnosed with EB-nTNKL via lymph node biopsy in Japan in order to better characterize its clinicopathological features and outcomes.

[RESULTS] The median age at diagnosis was 65 years (range 24-81), and most patients presented with advanced-stage (III/IV) disease, B symptoms, and high-risk International Prognostic Index scores. Elevated serum lactate dehydrogenase (median 614 U/L) and soluble interleukin-2 receptor (median 5247 U/mL) levels were observed in all cases. All cases expressed cytotoxic molecules (granzyme B and/or TIA-1), indicating a cytotoxic T/NK-cell phenotype, and 8 cases were CD8-positive. Responses to conventional chemotherapy were poor. The median overall survival was only 2.9 months, with 6 of 11 patients dying within 3 months of diagnosis.

[CONCLUSIONS] EB-nTNKL represents a distinct clinicopathological entity with a fulminant clinical course and profound chemoresistance, resulting in an extremely poor prognosis. However, differentiation from other EBV-associated T/NK-cell neoplasms, particularly those arising in younger patients, remains a diagnostic challenge and warrants further clinicopathological investigation. These dismal outcomes underscore an urgent need to develop more effective therapeutic strategies.