Acute agranular CD4-positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents

Abstract

A 63-year-old male presented with fever, a subcutaneous nodule, gingival hypertrophy, lacrimal gland enlargement, and no lymphadenopathy or hepatosplenomegaly, but had anemia, thrombocytopenia, and peripheral blood (PB) plus bone marrow (BM) involvement by leukemic cells. There was minimal response to multiagent chemotherapy and local radiotherapy, with a survival of 6.5 months from disease diagnosis. The PB and/or BM leukemic cells were evaluated using electron microscopy (EM), immunohistochemistry, flow-cytometric immunophenotyping, cytochemistry, cytogenetics, Southern blot analysis for gene rearrangement and Epstein-Barr virus (EBV), polymerase chain reaction for EBV and human herpes virus-6 (HHV-6), and in vitro culturing with inducing agents. The leukemic cells were agranular and monocytoid, with a hairy cell-like bone marrow biopsy infiltrate. Myeloperoxidase (MPO) and alpha-naphthyl butyrate esterase staining was negative, and periodic acid-Schiff staining was positive by light microscopy. Electron microscopy showed MPO negativity and a lack of parallel tubular arrays. The immunophenotype was CD3-, CD56+, CD4+, CD8-, CD15+, TCR1-, and TCR2-, with germline immunoglobulin and T-cell receptor genes and an abnormal karyotype (44XY, 5q-, -13, 13q+, -15). No genomic material for EBV or HHV-6 was detected. Cell cultures with butyrate and N,N-hexamethylene bis-acetamide suggested the possible induction of tumor cells to express a T-cell immunophenotype. A case of clonal acute natural killer (NK) cell leukemia with an unusual morphology (agranular) and unique phenotype (CD3-, CD56+, CD4+, CD15+) is presented. Unlike as 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.