A monoclonal antibody spike on serum protein electrophoresis is most characteristic of which plasma cell malignancy?

• A. Waldenström Macroglobulinemia
• B. Multiple Myeloma
• C. MGUS
• D. Amyloidosis

Answer: (B)

A monoclonal spike on serum protein electrophoresis signals production of a single type of immunoglobulin by a clone of cells. In multiple myeloma, malignant plasma cells overproduce one immunoglobulin (often IgG or IgA, sometimes light chains only), creating a sharp, narrow M-spike on SPEP. This pattern is the most characteristic feature of a malignant plasma cell disorder.

Waldenström macroglobulinemia can also show an M-spike, but it’s typically IgM and arises from lymphoplasmacytic lymphoma rather than true plasma cell myeloma. MGUS shows a small M-spike without end-organ damage and is not a malignant condition. Amyloidosis involves deposition of light chains rather than a prominent discrete M-spike on SPEP.