Monoclonal Gammopathies of Undetermined Significance (MGUS) Workup

Updated: Sep 23, 2021
  • 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 kidney 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 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.

To diagnose monoclonal gammopathy of renal significance, Castillo et al propose an algorithm that includes urinalysis in addition to kidney function and metabolic testing, and advises kidney biopsy if any of the following are presen [47] t:

  • Stage 3 acute kidney injury
  • Estimated glomerular filtration rate < 60 mL/min, with annual decline > 2 mL/min
  • Proteinuria > 1 g/24 h
  • Albumin:creatinine ratio > 30 mg/mmol
  • Fanconi syndrome