ACUTE AGRANULAR CD4-POSITIVE NATURAL-KILLER-CELL LEUKEMIA - COMPREHENSIVE CLINICOPATHOLOGICAL STUDIES INCLUDING VIROLOGICAL AND IN-VITRO CULTURE WITH INDUCING AGENTS

Background. A 63-year-old male presented with fever, a subcutaneous no dule, gingival hypertrophy, lacrimal gland enlargement, and no lymphad enopathy or hepatosplenomegaly, but had anemia, thrombocytopenia, and peripheral blood (PB) plus bone marrow (BM) involvement by leukemic ce lls. There was minimal response to multiagent chemotherapy and local r adiotherapy, with a survival of 6.5 months from disease diagnosis. Met hods. The PB and/or BM leukemic cells were evaluated using electron mi croscopy (EM), immunohistochemistry, flow-cytometric immunophenotyping , cytochemistry, cytogenetics, Southern blot analysis for gene rearran gement and Epstein-Barr virus (EBV), polymerase chain reaction for EBV and human herpes virus-6 (HHV-6), and in vitro culturing with inducin g agents. Results. The leukemic cells were agranular and monocytoid, w ith a hairy cell-like bone marrow biopsy infiltrate. Myeloperoxidase ( MPO) and alpha-naphthyl butyrate esterase staining was negative, and p eriodic acid-Schiff staining was positive by light microscopy. Electro n microscopy showed MPO negativity and a lack of parallel tubular arra ys. The immunophenotype was CD3-,CD56+,CD4+,CD8-,CD15+,TCR1-, and TCR2 - with germline immunoglobulin and T-cell receptor genes and an abnorm al karyotype (44XY, 5q-, -13, 13q+, -15). No genomic material for EBV or HHV-6 was detected. Cell cultures with butyrate and N,N-hexamethyle ne bis-acetamide suggested the possible induction of tumor cells to ex press a T-cell immunophenotype. Conclusion. A case of clonal acute nat ural killer (NK) cell leukemia with an unusual morphology (agranular) and unique phenotype (CD3-, CD56+, CD4+, CD15+) is presented. Unlike a s in other acute NK leukemias, EBV was negative; there was no evidence of HHV-6. The tumor cell, after culturing with differentiating agents , may have been induced to express a T-cell immunophenotype.