Malignant hematolymphoid disorders arising from NK cells have become widely recognized over the past decade. The two forms of NK-cell malignancy, aggressive NK-cell leukemia (ANKL) and extranodal NK-cell lymphoma of nasal type (ENKL) are both characterized by the proliferation of tumor cells with an NK-cell like immunophenotype. ANKL usually presents with bone marrow tumor cells accompanied by circulating leukemic cells, and hepatosplenomegalay is a common clinical feature. ENKL most frequently affects the nasal or paranasal regions, with cutaneous involvement also being common. Approximately 70 percent of ENKL present with localized tumor cells, and follow an indolent clinical course, but, in advanced cases, tumors rapidly expand and are frequently fatal. Tumor cells from both ANKL and ENKL are surface CD3- and CD56+ but differ in their expression of CD16. Epstein-Barr virus (EBV) is found in most cases of NK-cell leukemia/lymphoma, suggesting an oncogenic role, but patients may have biclonal or polyclonal populations of malignant cells based on differential EBV genome incorporation. NK-cell neoplasms are frequently resistant to chemotherapy due to p-glycoprotein expression and associated multidrug resistance. The prognoses of both localized and advanced stages of NK-cell malignancies are worse than most other lymphoid malignancies, but studies are currently underway to assess the safety and efficacy of novel chemoradiotherapy regimens for the treatment of these neoplasms.
2005 by The Japanese Society for Lymphoreticular Tissue Research