A 72-year-old man presents with leukocytosis (30 × 10⁹/L-40 × 10⁹/L) with lymphocytosis (80%), monocytopenia, and anemia for 10 years. Peripheral smear revealed cells with cytoplasmic projections and atypical lymphocytes (panel A [Giemsa stain; original magnification ×1000]). A bone marrow biopsy showed areas of trilineage hematopoiesis and an interstitial infiltrate of lymphoid cells (panel B [hematoxylin and eosin (H&E) stain]) with irregular nuclei and ample cytoplasm (panel C [H&E stain]). Immunohistochemistry revealed cells double positive for PAX5 (brown) and tartrate-resistant acid phosphatase (red; panel D), PAX5 (brown) and CD103 (red; panel E), annexin (panel F), and BRAF^V600E (panel G) diagnostic of hairy cell leukemia (HCL). A second distinct population dual positive for PAX5 (brown) and CD5 (red; panel H) in combination with LEF-1 (panel I), and negative for cyclin D1/SOX11, indicated synchronous involvement by CD5⁺ lymphoproliferative disorder (LPD). Flow cytometry of marrow confirmed 2 clonal B-cell populations: the first (red) was CD19⁺CD5⁻ (panel J), CD22⁺CD11c⁺ (panel K), CD20⁺CD25⁺CD103⁺CD123⁺CD23⁻ (not shown), and λ light chain–positive (panel L), diagnostic of HCL. A second population (magenta) was CD19⁺CD5⁺ (panel J), CD22⁺CD11c⁻ (panel K), CD20⁺ (moderate) CD23⁺ (spectrum) CD43⁻CD200⁻CD103⁻ (not shown), and κ light chain–positive (panel L), representing atypical chronic lymphocytic leukemia. B-cell clonality testing by immunoglobulin heavy chain polymerase chain reaction showed 3 significant peaks (panel M) consistent with 2 distinct clonal B-cell populations. The patient was initially treated with splenectomy, and later with trametinib (MEK inhibitor) and dabrafenib (BRAF inhibitor).

This case highlights the indolent course of HCL and its recognized association with other B-cell LPD.