Monoclonal Gammopathies of Undetermined Significance (MGUS) Workup

Updated: Feb 11, 2020
  • Author: Suzanne R Fanning, DO; Chief Editor: Emmanuel C Besa, MD  more...
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Approach Considerations

The workup for monoclonal gammopathies of uncertain significance (MGUS) includes the following:

  • Complete metabolic panel - For example, to evaluate renal function, calcium, uric acid, and lactate dehydrogenase (LDH) [35]
  • Complete blood cell count (CBC) with differential - To evaluate for anemia, thrombocytopenia, and neutropenia
  • Tests for beta2 microglobulin and C-reactive protein - For prognostic information
  • Serum and urine electrophoresis with immunofixation - Diagnostic test of choice
  • Quantitative immunoglobulin measurements - To follow up the progress of the monoclonal gammopathy
  • Measurement of the proliferative rate of the plasma cells or plasma cell labeling index (value is low)
  • Serum electrophoresis
  • Serum free light chain (FLC) assay - Beneficial for prognostic purposes
  • Complete skeletal survey to assess for lytic lesions
  • Unilateral bone marrow aspiration and biopsy - To quantify the percentage of plasma cells and to assess for abnormal cytogenetics [36]

Bone marrow examination is recommended as part of the diagnostic workup for all patients with IgA and IgM M-proteins. In patients with apparent IgG MGUS, bone marrow examination is typically not recommended unless the serum M-protein level is greater than 1.5 g/dL or end-organ damage is evident. [3]

Ng et al reported improved quantification of marrow involvement through the use of CD138 immunostaining of bone marrow trephine specimens. [37] For the importance of immunophenotypic analysis, see Jerez et al. [38]

MGUS is characterized by the following:

  • Serum M-protein value less than 3 g/dL
  • Fewer than 10% plasma cells in the bone marrow
  • No or only small amounts of Bence-Jones protein in the urine
  • Absence of lytic bone lesions
  • No related anemia, hypercalcemia, renal failure, or any related end-organ damage

In patients with recently diagnosed MGUS, serum electrophoresis should be repeated after 3 months to exclude early myeloma. If the results are stable, the test should be repeated in 6 months. Patients should be aware that the evolution of MGUS to multiple myeloma can be abrupt; therefore, they should be reexamined promptly if their clinical condition deteriorates.