A patient with bone pain, anemia, and renal impairment has an M-protein spike on SPEP. What is the most likely diagnosis?

• A. Waldenström macroglobulinemia
• B. Multiple myeloma
• C. Chronic lymphocytic leukemia
• D. Acute lymphoblastic leukemia

Answer: (B)

A monoclonal plasma cell neoplasm that secretes a single type of immunoglobulin (an M-protein) with bone-related damage and organ dysfunction is the underlying idea here. The presence of an M-spike on SPEP points to a monoclonal gammopathy produced by malignant plasma cells. In multiple myeloma, these malignant cells accumulate in the bone marrow and drive bone destruction, leading to bone pain from lytic lesions. They also crowd out normal blood cell production, causing anemia, and they release light chains that can overwhelm the kidneys, causing renal impairment.

Understanding the other possibilities helps reinforce why this fits best. Waldenström macroglobulinemia also involves an M-protein, but it is usually IgM and tends to cause hyperviscosity symptoms such as vision changes or mucosal bleeding rather than prominent bone lesions and marked CRAB features. Chronic lymphocytic leukemia and acute lymphoblastic leukemia involve malignant lymphocytes and have different hallmark presentations (lymphadenopathy with smear findings or lymphoblasts, respectively) and do not typically present with an M-spike as the central clue.

So the combination of bone pain, anemia, renal impairment, and an M-spike strongly points to multiple myeloma.