M-spike on serum protein electrophoresis indicates which type of disease?

• A. Iron deficiency anemia
• B. Plasma cell dyscrasia such as multiple myeloma, MGUS, or Waldenström macroglobulinemia
• C. Non-Hodgkin lymphoma
• D. Aplastic anemia

Answer: (B)

An M-spike on serum protein electrophoresis signals a monoclonal gammopathy caused by a clonal population of plasma cells or B cells producing one type of immunoglobulin. This appears as a sharp, narrow spike in the gamma region (or sometimes the beta region) on SPEP, reflecting a single immunoglobulin band rather than a broad, polyclonal increase.

The classic conditions associated with an M-spike are plasma cell dyscrasias, such as multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström macroglobulinemia. In these disorders, a single clone of cells overproduces a specific immunoglobulin (for example, IgG kappa, IgM, etc.), leading to the detectable M-spike.

Iron deficiency anemia does not involve excess production of a single immunoglobulin, so it does not create an M-spike. Non-Hodgkin lymphoma can have various immunoglobulin abnormalities but is not defined by a prominent monoclonal spike on SPEP. Aplastic anemia is a marrow failure with pancytopenia and likewise lacks a monoclonal immunoglobulin spike. If an M-spike is seen, it prompts evaluation for a monoclonal gammopathy and related plasma cell–related disorders, with follow-up testing to define the exact condition.