Diagnosis and management of natural killer-cell malignancies

Natural killer (NK)-cell malignancies are uncommon neoplasms, which have been referred to as polymorphic reticulosis or angiocentric T-cell lymphomas in the past. In the current WHO classification, they are categorized as extranodal NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia. NK-cell malignancies show a geographical predilection for Asian and South American populations and are rare in the west. Pathologically, NK-cell lymphomas show a polymorphic neoplastic infiltrate with angioinvasion and angiodestruction. The lymphoma cells are CD2(+), cytoplasmic CD3ε(+) and CD56(+), with germline T-cell receptor gene. There is an almost invariable clonal episomal infection with Epstein-Barr virus. Clinically, NK-cell lymphomas can be classified into nasal, non-nasal and aggressive lymphoma/leukemia subtypes. Most nasal NK-cell lymphomas present with stage I/II disease. The early use of radiotherapy, either alone or concomitantly/sequentially with chemotherapy, is the most important factor in achieving successful treatment. Many stage I/II patients receiving radiotherapy alone fail systemically, so the use of chemotherapy is also considered necessary. Chemotherapy is indicated for stage III/IV nasal NK-cell lymphoma, and the non-nasal and aggressive subtypes. Recent regimens that incorporate the use of L-asparaginase have resulted in substantial improvements in outcome in high-risk, refractory or relapsed patients. High-dose chemotherapy and hematopoietic stem-cell transplantation with autologous or allogeneic hematopoietic stem cells may be beneficial to selected patients. Prognostication of patients with clinical prognostic models and presentation circulating Epstein-Barr DNA load may be useful in the stratification of patients for various treatment modalities.