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Monoclonal Gammopathy of Undetermined Significance (MGUS)

By James R. Berenson, MD, President and Chief Medical Officer, Institute for Myeloma and Bone Cancer Research

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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 MGUS increases with age, from 1% of people aged 25 yr to > 5% of people > 70 yr. MGUS may occur in association with other disorders (see Table: Classification of Plasma Cell Disorders), in which case M-proteins may be antibodies produced in large amounts in response to protracted antigenic stimuli.

MGUS usually is asymptomatic, but peripheral neuropathy can occur, and patients are at higher risk of enhanced bone loss and fractures. Although most cases are initially benign, up to 25% (1%/yr) progress to myeloma or a related B-cell disorder, such as macroglobulinemia, amyloidosis, or lymphoma.

Diagnosis 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 (< 300 mg/24 h). MGUS is differentiated from other plasma cell disorders because M-protein levels remain relatively stable over time 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) may benefit from treatment with bisphosphonates. Every 6 to 12 mo, patients should undergo clinical examination and serum and urine protein electrophoresis to evaluate for disease progression.