LYMPHOPROLIFERATIVE DISORDERS OF NATURAL-KILLER-CELLS

Natural killer (NK) cells are a distinct non-T, non-B lineage of lymph ocytes that mediate major histocompatibility complex-unrestricted cyto toxicity. Morphologically they are large granular lymphocytes, and phe notypically they commonly express CD16 and CD56 antigens, without expr essing cell surface CD3. Although the developmental pathway of NK cell s is not fully understood, they arise from CD34(+) hematopoietic stem cells and, at least in part, differentiate in the bone marrow. They ga in byctoplasmic CD3 gamma delta epsilon zeta antigens during maturatio n, and lose cytoplasmic CD3 gamma delta epsilon thereafter until the t erminal maturation. Lymphoproliferative disorders of NK cells include NK cell-lineage granular lymphocyte-proliferative disorders (NK-GLPD), NK-cell lymphoma, and acute leukemia of NK-cell lineage. NK-GLPD are relatively rare. Most patients exhibit a chronic indolent clinical cou rse: and do not require specific treatment. However, some patients exh ibit an aggressive clinical course, and die of the disease despite ext ensive chemotherapy. This aggressive type NK-GLPD is caused by Epstein -Barr virus (EBV). Patients with NK-cell lymphoma are rare, and often exhibit necrotic lesion and angiocentric morphology. This tumor is mai nly found in the nasal tract, but the true incidence of NK-cell lympho ma in nasal lymphomas is not known. Probably many lymphomas arising fr om the nasal cavity, but not from paranasal sinuses, are of NK-cell li neage. NK-cell lymphoma is also caused by EBV, and is resistant to com bination chemotherapy. Acute leukemia of NK-cell lineage is very rare. Several cases of acute lymphoblastic leukemia and a single case of bl ast crisis of chronic myelogenous leukemia have been documented to hav e leukemic blasts characteristic of NK cells. However, the precise lin eage and differentiation stage of the leukemic blasts have not been de lineated.