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ESSENTIALS OF DIAGNOSIS

  • Monoclonal immunoglobulin (ie, paraprotein) in the serum (less than 3 g/dL [less than 30 g/L]) or urine.

  • Clonal plasma cells in the bone marrow less than 10% (if performed).

  • No symptoms and no organ damage from the paraprotein.

GENERAL CONSIDERATIONS

MGUS is present in 1% of all adults (3% of those over age 50 years and more than 5% of those over age 70 years). Among all patients with paraproteins, MGUS is far more common than plasma cell myeloma. MGUS is defined as bone marrow monoclonal plasma cells less than 10% in the setting of a paraprotein (serum M-protein less than 3 g/dL [30 g/L]) and the absence of plasma cell–related end-organ damage. If an excess of serum free light chains (kappa or lambda) is established, the kappa to lambda ratio is 100 or less or 0.01 or greater. In approximately one-quarter of cases, MGUS progresses to overt malignant disease in a median of one decade. The transformation of MGUS to plasma cell myeloma is approximately 1% per year. Two adverse risk factors for progression of MGUS to a plasma cell or lymphoid malignancy are an abnormal serum kappa to lambda free light chain ratio and a serum monoclonal protein (M-protein) level 1.5 g/dL or greater. Patients with MGUS have shortened survival (median 8.1 years vs 12.4 years for age- and sex-matched controls). In addition, 12% of patients with MGUS will convert to primary amyloidosis in a median of 9 years. Plasma cell myeloma, smoldering plasma cell myeloma, and MGUS must be distinguished from reactive (benign) polyclonal hypergammaglobulinemia (common in cirrhosis or chronic inflammation).

LABORATORY FINDINGS

To establish the diagnosis, serum and urine should be sent for PEP and IFE to search for a monoclonal protein; serum should be sent for free light chain analysis and quantitative immunoglobulins. Additional tests include a hemoglobin and serum albumin, calcium, and creatinine. If these additional tests are normal (or if abnormal but otherwise explained), then a bone marrow biopsy is usually deferred provided the serum M-protein is less than 3 g/dL (less than 30 g/L). In asymptomatic individuals, a skeletal survey (radiographs) is performed, but if there are some bone complaints or a question regarding bone disease, MRI or PET/CT imaging is preferred. MGUS is diagnosed if patients do not meet the criteria for smoldering plasma cell myeloma or plasma cell myeloma.

TREATMENT

Patients with MGUS are observed without treatment.

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Atkin  C  et al. What is the significance of monoclonal gammopathy of undetermined significance? Clin Med (Lond). 2018 Oct;18(5):391–6.
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Kyle  RA  et al. Long-term follow up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018 Jan 18;378(3):241–9.
[PubMed: 29342381]  
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Willrich  MAV  et al. Laboratory testing for monoclonal gammopathies: focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. ...

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