Plasma cell leukemia presenting as “lymphocytosis”

A 70-year-old man presented with anemia and “lymphocytosis” (panel A; Wright-Giemsa stain, original magnification ×1000). Bone marrow biopsy revealed diffuse small neoplastic cells (panel B; hematoxylin and eosin stain, original magnification ×200) morphologically similar to the “lymphocytes” in peripheral blood and resembling low-grade B-cell lymphoma. These cells strongly expressed CD20, PAX5, cyclin D1, CD138, and λ (panels C-G; [C] CD20 stain, [D] cyclin D1 stain, [E] CD138 stain, [F] λ stain, [G] κ stain, [C-G] original magnification ×400), but were negative for CD5, SOX11, and κ. Flow cytometry showed they expressed bright CD38, CD138, CD20, CD56, and monotypic cytoplasmic λ, but lacked CD19, CD45 (panel H), and surface light chain expression. Immunostains on the blood clot showed the circulating “lymphocytes” had a similar immunophenotype: strongly positive for CD138 and λ (panels I-K; [I] hematoxylin and eosin stain, original magnification ×200, insert, ×1000; [J] CD138 stain, original magnification ×400; [K] λ stain, original magnification ×400). Fluorescence in situ hybridization detected IGH/CCND1 translocation and 17p/p53 deletion. Serum protein electrophoresis showed free λ paraproteinemia. Positron emission tomography/computed tomography showed skeletal lytic lesions. He was diagnosed with plasma cell leukemia (PCL), small cell variant.

Although the morphology and CD20, PAX5, and cyclin D1 expression raised the possibility of mantle cell lymphoma, the strong CD138 expression but lack of CD45 expression confirmed a diagnosis of PCL. The small cell variant of PCL is rare and may cause diagnostic challenge by mimicking low-grade B-cell lymphoma, especially when cells express CD20 and cyclin D1, as seen in this case. A thorough workup is critical in reaching the correct diagnosis.