A CBC shows anemia with rouleaux on smear, M-spike on electrophoresis, and hypercalcemia. What is the presumptive diagnosis?

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Rouleaux on a smear reflect high serum protein, typically from a monoclonal immunoglobulin, and a monoclonal spike on serum protein electrophoresis confirms a single clone producing that protein. When this is paired with anemia and hypercalcemia, it points to end-organ damage from malignant plasma cells—bone destruction driving the calcium rise and decreased red cell production causing anemia. This combination is classic for multiple myeloma, where a monoclonal immunoglobulin is produced by clonal plasma cells that infiltrate bone marrow and disrupt normal bone remodeling.

Waldenström macroglobulinemia can also show rouleaux and a monoclonal protein, but hypercalcemia and bone-destructive features are not typical. MGUS has an M-spike but lacks CRAB features like anemia or hypercalcemia. Acute lymphoblastic leukemia doesn’t usually present with a monoclonal spike on electrophoresis.