A 60-year-old man presents with splenomegaly, leukocytosis, and peripheral blood showing villous lymphocytes with cytoplasmic projections that are shorter and less numerous than in hairy cell leukemia. Flow cytometry shows CD20+, CD11c+, CD25−, CD103−, CD123−. Which diagnosis is most likely?

• A B-cell prolymphocytic leukemia
• B Splenic marginal zone lymphoma (SMZL)
• C Splenic diffuse red pulp small B-cell lymphoma
• D Hairy cell leukemia variant (HCL-v) ✓

Explanation

Hairy cell leukemia variant (HCL-v) presents with splenomegaly and villous lymphocytes but typically shows higher WBC counts than classic HCL, and the cells lack the characteristic immunophenotype: HCL-v is CD25− and CD103 variable (often dim or negative), whereas classic HCL is strongly CD25+ and CD103+. This distinction is therapeutically important because HCL-v does not respond well to purine analogs (cladribine). SMZL is also CD25− but lacks the prominent cytoplasmic projections.

Reference: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th (2017) ed.

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Written and medically reviewed by the StethoPrep medical team.