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Key Features

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

  • Clonal plasma cells in the bone marrow < 10% (if performed)

  • No symptoms and no organ damage from the paraprotein

  • MGUS is present in

    • 1% of all adults

    • 3% of those over age 50 years

    • > 5% of those over age 70 years

  • Among all patients with paraproteins, MGUS is far more common than plasma cell myeloma

Clinical Findings

  • Defined as bone marrow clonal plasma cells < 10% in the setting of a paraprotein (serum M-protein < 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 (otherwise, this is diagnostic of plasma cell myeloma)

  • 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 ~ 1% per year

  • Twelve percent of patients with MGUS will convert to amyloidosis in a median of 9 years

  • Plasma cell myeloma, smoldering plasma cell myeloma, and MGUS must be distinguished from reactive (benign) polyclonal hypergammaglobulinemia (which is commonly seen in cirrhosis or chronic inflammation)

Diagnosis

  • To establish the diagnosis,

    • Serum and urine should be sent for protein electrophoresis (PEP) and immunofixation electrophoresis (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 abnormality is otherwise explained), then a bone marrow biopsy is usually deferred provided the serum M-protein is < 3 g/dL (< 30 g/L)

  • Radiographs are obtained in asymptomatic individuals

  • MRI or PET-CT imaging is preferred if there are some bone complaints or a question regarding bone disease

  • MGUS is diagnosed if patients do not meet the criteria for smoldering plasma cell myeloma or plasma cell myeloma

Treatment

  • None; patients are observed

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