Natural Killer Cell Neoplasms

Neoplasms of natural killer (NK) cells are a group of uncommon but highly aggressive malignancies with a strong geographic predilection, and predominantly involving extranodal sites, particularly the nasal/nasopharyngeal region, and sometimes extranasal areas such as the skin and gastrointestinal tract. This group of tumors is characterized: 1) pathologically by an angiocentric and angiodestructive infiltrate of lymphoid cells that can span a broad cytologic spectrum, and that frequently contain cytologic granules; 2) phenotypically by the expression of CD2, cytoplasmic CD3ε and CD56, but not surface CD3 or T cell receptor (TCR); 3) genotypically by a germline configuration of TCR genes; and 4) by a very strong association with Epstein-Barr virus (EBV). According to the clinicopathologic features, they are classified by the World Health Organization (WHO) into: 1) extranodal NK/T cell lymphoma; and 2) aggressive NK cell leukemia. The entity currently known as blastic NK cell lymphoma is probably not a genuine NK cell neoplasm. NK cell neoplasms are one of the most aggressive hematolymphoid malignancies, and are often resistant to conventional combination chemotherapy.