Natural killer (NK)/T-cell lymphomas and NK-cell leukemias are aggressive malignancies. Occurring worldwide, they show a predilection for Asian and South American populations. Neoplastic cells are surface CD3-, cytoplasmic CD3ε+, CD56+, cytotoxic-molecule positive, Epstein-Barr virus (EBV) positive, with germline T-cell receptor gene. Lymphomas occur commonly in the nasal and upper aerodigestive region. Occasional cases present in the skin, salivary gland, testis, and gastrointestinal tract. Rare cases are disseminated with lymphadenopathy, hepatosplenomegaly, and a leukemic phase. Positron emission tomography computed tomography is useful in staging, as lymphomas are 18-fluorodeoxyglucose avid. Quantification of circulating EBV DNA is an accurate biomarker of tumor load. Nasal NK/T-cell lymphomas present mostly with stage I/II disease. Concomitant/sequential chemotherapy and radiotherapy is standard treatment. Radiotherapy alone is inadequate because of high systemic failure rate. For stage III/IV nasal, nonnasal, and disseminated lymphomas, systemic chemotherapy is indicated. Regimens containing l-asparaginase and drugs unaffected by P-glycoprotein are most effective. Hematopoietic stem cell transplantation (HSCT) is not indicated for early-stage nasal lymphomas. HSCT for lymphomas not in remission has poor results. In advanced-stage nasal, nonnasal, disseminated, or relapsed lymphomas, HSCT may be considered when remission is achieved. Prognostic modeling and EBV DNA monitoring may be useful in risk stratification for HSCT.
