Hairy cell leukemia-variant is rare. Only a small number of cases have been reported in the literature with little cytogenetic or molecular data available. In this study, we describe the clinicopathologic and genetic features of 23 patients with
hairy cell leukemia-variant (16 men and 7 women) with a median age of 70 years. Most patients had
splenomegaly (90%),
leukocytosis (77%), and
lymphocytosis (82%); no patients had monocytopenia. Histologically, the bone marrow biopsy specimens showed a mixed pattern of predominantly interstitial and lesser intrasinusoidal infiltration by leukemic cells. In bone marrow aspirate smears most cells had villous cytoplasmic features and a small nucleolus. We describe unusual sites of
hairy cell leukemia-variant involvement in 4 patients, including brain, omentum, terminal ileum, and skin at the time of initial presentation. Immunophenotyping showed monotypic B-cells positive for pan B-cell
antigens, CD11c, and CD103, and negative for CD25 and
annexin A1. Conventional cytogenetic or fluorescence in situ hybridization analysis showed deletions of 17p13/TP53 and 11q22/ATM gene in 5/12 (42%) and 2/9 (22%) cases, respectively. Sequencing of the variable region of IGVH showed mutations (>2% deviation from germline) in 40% of the cases assessed. MAP2K1 mutation (p.C121S) was seen in 1 of 14 (7%) patients tested. No BRAF V600E mutations were detected. The patients were treated in a heterogeneous manner, but most often with
therapies designed for classical
hairy cell leukemia and the 5-year overall survival was 84%. In summary,
hairy cell leukemia-variant exhibits a heterogeneous spectrum of clinical, morphologic, immunophenotypic, and genetic features that may overlap with classic
hairy cell leukemia and other hairy cell-like B-cell
neoplasms. A subset of patients can have an aggressive
clinical course. In our experience MAP2K1 mutations are uncommon in this disease.