2026 Volume 102 Issue 3 Pages 105-113
Extranodal NK/T-cell lymphoma (ENKTL) is a rare, aggressive Epstein–Barr virus (EBV)-associated malignancy. The 5th edition of the WHO classification refined their nomenclature by removing “nasal type” and introducing related entities to reflect updated biological insights. This review synthesizes recent advances in epidemiology and molecular pathogenesis in ENKTL, highlighting recurrent driver gene alterations, particularly frequent mutations in X-linked genes such as DDX3X and MSN, alongside TP53 mutations and PD-L1 structural variations that facilitate immune evasion. We also discuss novel mouse models that replicate the ENKTL niche, revealing how Trp53 loss and the EBV oncoprotein LMP1 synergistically remodel the tumor microenvironment to promote lymphomagenesis. Therapeutically, while L-asparaginase-based regimens including SMILE and P-GemOx remain the standard of care, emerging immune checkpoint inhibitors have demonstrated encouraging efficacy, particularly in combination with chemotherapy. This review provides an integrated perspective on the evolving landscape of diagnosis, disease biology, and translational treatment strategies for NK/T-cell lymphoproliferative disorders.
