A 63-year-old woman being followed for splenomegaly presented with lymphocytosis (hemoglobin, 14 g/dL; neutrophils, 2.5 × 109/L; lymphocytes, 8.5 × 109/L; monocytes, 0.7 × 109/L; platelets, 200 × 109/L). A blood smear showed 40% medium-sized lymphocytes with abundant cytoplasm with circumferential projections, similar to those of classic hairy cells. The nucleus had condensed chromatin with a conspicuous nucleolus (panels A-F). Flow cytometry revealed 45% clonal B lymphocytes that expressed CD19/CD20/CD22/CD103/CD11c and a lack of CD5/CD10/CD123/CD25/CD200. The BRAFV600E mutation was negative, confirming the diagnosis of hairy cell leukemia-variant (HCL-v).
Despite morphologic similarities, HCL-v is not biologically related to classic HCL (cHCL). HCL-v should be suspected in cases with splenomegaly associated with cytopenias, a normal monocyte count, and lymphocytosis characterized by hairy cells with prominent nucleoli. The immunophenotype CD103pos/CD11cbright/CD123neg/CD25neg supports the diagnosis. CD200 is also useful as it is highly expressed in cHCL and negative in HCL-v. The distinction from splenic diffuse red pulp lymphoma is important and relies on the presence of lymphocytosis with prominent nucleoli observed in HCL-v. The BRAFV600E mutation is found in almost all cases of cHCL but not in HCL-v. TP53 abnormalities and MAP2K1 mutations are found in nearly half of the cases of HCL-v.