A 70-year-old woman presented with a 4-month history of severe back pain, generalized weakness, and 12-kg weight loss. A spine MRI revealed multiple lytic lesions and collapses of T5 and T7. She had mid-thoracic tenderness and hepatosplenomegaly, but no lymphadenopathy. Hemoglobin was 10.2 g/dL, leukocytes 50.3 × 109/L (88% lymphocytes), and platelets 130 × 109/L. Peripheral smear showed many smudge-cells with an immunophenotype consistent with chronic lymphocytic leukemia (CLL). Serum protein electrophoresis was unremarkable. A bone marrow examination showed marked infiltration with lymphocytes, and increased numbers of plasma cells (18%). Many plasma cells contained 1 to 3 large, clear, PAS-negative cytoplasmic vacuoles (see figure panels). These clinical and morphologic findings raised the suspicion of μ-heavy-chain disease (μ-HCD). Serum immunofixation revealed an M-band typed as IgM without corresponding light chain, thus confirming the diagnosis. A 24-hour urine collection contained 2.84 g of protein consisting of free κ-light chains. The patient received chemotherapy and local radiotherapy with substantial improvement.
μ-HCD is a rare B-cell neoplasm resembling CLL, but differing clinically by lytic bone lesions, hepatosplenomegaly, and the absence of lymphadenopathy. This heavy-chain disorder is characterized by synthesis of monoclonal μ-chain fragments lacking VH region and in part CH1, with an inability to bind light-chain. Associated light-chain proteinuria and skeletal involvement may occur. The absence of M-component on routine electrophoresis may preclude recognition of the disorder. The morphologic clues in this case were the plasma cells with striking vacuoles.
