Epstein-Barr Virus-Associated T/NK-Cell Neoplasms

Epstein-Barr virus (EBV)-associated T- and natural killer (NK)-cell neoplasms encompass a heterogeneous spectrum, ranging from persistent lymphoproliferative disorders (e.g., severe mosquito bite allergy, systemic chronic active EBV disease) to highly aggressive malignancies (e.g., extranodal NK/T-cell lymphoma [ENKTL], aggressive NK-cell leukemia). Genomic and epigenetic studies have revealed shared host genetic alterations-most notably in JAK-STAT signaling, epigenetic regulators, TP53, and DDX3X-supporting a pathogenic and clinicobiological continuum across these disorders. Defective EBV further reshapes viral gene expression programs and contributes to oncogenesis. l-asparaginase-based chemoradiotherapy has improved outcomes in early-stage ENKTL; however, effective treatments for advanced-stage disease and other EBV-associated T/NK-cell neoplasms remain limited. Emerging molecular subclassifications and large-scale prospective cohorts can help clarify disease heterogeneity and accelerate the development of precision therapeutic strategies.