Diagnostic and Monitoring Tests for Monoclonal Gammopathy of Undetermined Significance (MGUS)
For diagnosing and monitoring MGUS, a risk-stratified approach based on initial laboratory findings should be implemented, with bone marrow examination and imaging studies reserved for patients with higher risk features or abnormal laboratory results. 1
Initial Diagnostic Workup
Essential Laboratory Tests
- Complete blood count, serum calcium, and creatinine values to rule out end-organ damage 1
- Qualitative test for urine protein; if positive, perform urine protein electrophoresis and immunofixation 1
- Serum protein electrophoresis (SPEP) to detect and quantify M-protein 1
- Serum immunofixation electrophoresis (SIFE) to characterize the heavy and light chains of M-protein 1
- Quantitative immunoglobulin levels (IgG, IgA, and IgM) 1
- Serum free light chain (FLC) assay with kappa/lambda ratio assessment 1
Risk Stratification
After initial testing, patients should be stratified into risk categories:
Low-Risk MGUS
- Serum M-protein <15 g/L
- IgG type
- Normal FLC ratio 1
Intermediate/High-Risk MGUS
- Serum M-protein >15 g/L, and/or
- IgA or IgM protein type, and/or
- Abnormal FLC ratio 1
Additional Testing Based on Risk Category
For Low-Risk MGUS
- Baseline bone marrow examination or skeletal radiography is not routinely indicated if clinical evaluation and laboratory tests suggest MGUS 1
- Bone marrow examination is required only if the patient has unexplained anemia, renal insufficiency, hypercalcemia, or bone lesions 1
For Intermediate/High-Risk MGUS
- Bone marrow aspirate and biopsy should be performed at baseline to rule out underlying plasma cell malignancy 1
- Both conventional cytogenetics and fluorescence in situ hybridization (FISH) should be performed on bone marrow examination 1
- If available, plasma cell labeling index and search for circulating plasma cells using flow cytometry are useful 1
- For IgM MGUS, a computed tomography scan of the abdomen should be done to check for asymptomatic retroperitoneal lymph nodes 1
- Additional tests for patients with evidence of multiple myeloma or Waldenström's macroglobulinemia: lactate dehydrogenase, β-2-microglobulin, and C-reactive protein 1
Imaging Studies
- For non-IgM MGUS with higher risk features: skeletal survey 1
- For IgM MGUS: CT scan of chest, abdomen, and pelvis 1
- Low-dose whole-body CT may be a good alternative to conventional X-rays as suggested by the IMWG consensus panel 1
- Dual-energy X-ray absorptiometry (DXA) should be considered to evaluate bone mineral density, especially when other risk factors for osteoporosis are present 1
Monitoring Recommendations
Low-Risk MGUS
- Repeat SPEP in 6 months after diagnosis 1
- If stable, follow-up every 2-3 years or when symptoms suggestive of plasma cell malignancy arise 1
Intermediate/High-Risk MGUS
Important Considerations and Pitfalls
- MGUS must be distinguished from smoldering multiple myeloma (SMM), which has a higher risk of progression (10% per year for SMM versus 1% per year for MGUS) 1
- The risk of progression to malignancy does not diminish over time, necessitating lifelong follow-up 1
- Patients should be instructed to contact their physician if there is any change in their clinical condition 1
- Bone marrow examination is always required if a patient with presumed MGUS has unexplained anemia, renal insufficiency, hypercalcemia, bone lesions, or suspicion of AL amyloidosis 1
- Treatment is not indicated for MGUS unless it is part of a clinical trial 1
- In cases of significant proteinuria or renal insufficiency, kidney biopsy may be indicated to demonstrate monoclonal deposits 1
By following this risk-stratified approach to testing and monitoring, clinicians can appropriately manage MGUS patients while minimizing unnecessary invasive procedures and optimizing follow-up strategies.