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Monoclonal Gammopathy of Undetermined Significance (MGUS)


James R. Berenson

, MD, Institute for Myeloma and Bone Cancer Research

Reviewed/Revised Oct 2021 | Modified Sep 2022
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Monoclonal gammopathy of undetermined significance (MGUS) is the production of M-protein by noncancerous plasma cells in the absence of other manifestations typical of multiple myeloma.

The incidence of monoclonal gammopathy of undetermined significance (MGUS) increases with age, from 1% of people aged 25 years to > 5% of people > 70 years. MGUS may occur in association with other disorders (see table Classification of Plasma Cell Disorders Classification of Plasma Cell Disorders Classification of Plasma Cell Disorders ), in which case M-proteins (monoclonal immunoglobulin proteins, which may consist of both heavy and light chains or of only a light chain) may be antibodies produced in large amounts in response to protracted antigenic stimuli.

Diagnosis of MGUS is usually suspected when M-protein is incidentally detected in blood or urine during a routine examination. On laboratory evaluation, M-protein is present in low levels in serum (< 3 g/dL) or urine (< 200 mg/24 hours). MGUS is differentiated from malignant plasma cell disorders because M-protein levels are lower and lytic bone lesions, anemia, and renal dysfunction are absent. Because of fracture risk, baseline evaluation with a skeletal survey (ie, plain x-rays of skull, long bones, spine, pelvis, and ribs) and bone densitometry should be done. Bone marrow shows only mild plasmacytosis (< 10% of nucleated cells).

No antineoplastic treatment is recommended. However, recent studies suggest that MGUS patients with associated bone loss (osteopenia or osteoporosis Osteoporosis Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more Osteoporosis ) may benefit from treatment with intravenous bisphosphonates but less frequently than the monthly treatments usually required to treat patients with multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more Multiple Myeloma . Every 6 to 12 months, patients should undergo clinical examination and serum and urine protein electrophoresis to evaluate for disease progression.

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