Pathogenesis and treatment of extranodal natural killer/T-cell lymphoma

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is one of the uncommon subtypes of malignant lymphoma, and predominantly occurs in the nasal or paranasal areas and less frequently in the skin. Previously, its prognosis was poor due to the expression of P-glycoprotein, which actively exports several anticancer agents outside the lymphoma cells. However, in recent years, novel therapeutic approaches such as simultaneous chemoradiotherapy or l-asparaginase-based regimens including SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) improved the response to therapy and survival of ENKL patients. Epstein-Barr virus (EBV) is present in lymphoma cells of almost all patients, accounting for the pathogenesis of ENKL. Fragmented EBV-DNA is released from tumor cells, and can be detected in the peripheral blood of patients. The EBV-DNA copy numbers are associated with tumor burden, and can predict the prognosis of ENKL, as well as the toxicity against chemotherapy. Based on this recent progress, ENKL is currently categorized as a lymphoma with intermediate prognosis, but the overall treatment results are not satisfactory. Further improvement of the prognosis of ENKL is therefore warranted, including the optimal use of hematopoietic stem cell transplantation (HSCT).