Monoclonal Protein on Serum Protein Electrophoresis (M Component)

Differential Diagnosis

Multiple myeloma

Waldenstrom macroglobulinemia

Monoclonal gammopathy of unknown significance (MGUS)

Low concentration of monoclonal immunoglobulins (LCMI)

Heavy chain disease

Suggested Additional Lab Testing

For multiple myeloma:

  • In addition to SPEP followed by immunofixation, quantitative serum immunoglobulin should be performed, because the M component must be greater than3 g/dL in the serum.

  • Bone marrow aspirate may be useful to show that at least 10% of the nucleated blood cells are plasma cells.

  • Bone marrow biopsy may be useful to show aggregates of plasma cells in focal or diffuse patterns.

  • CBC often reveals a normochromic normocytic anemia.

  • Peripheral blood smear often shows RBCs in a stacked or rouleaux formation.

For Waldenstrom macroglobulinemia:

  • Immunofixation to identify the M component as an IgM immunoglobulin with a quantitative IgM level greater than 3 g/dL

  • Serum viscosity is usually increased.

  • Peripheral blood smear often shows RBC aggregates in a rouleaux formation.

For heavy chain disease:

  • Immunofixation reveals the heavy chain as alpha, gamma, or mu.

  • Bone marrow examination may be informative.


  • Quantitative determination of the serum M component to demonstrate that an IgG or IgM monoclonal protein is less than 3.0 g/dL or an IgA monoclonal protein is less than 2.0 g/dL, or that a Bence-Jones protein is less than or equal to 1.0 g in a 24-hour urine specimen

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