Differential Diagnosis

Multiple myeloma

Waldenstrom macroglobulinemia

Monoclonal gammopathy of unknown significance (MGUS)

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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