Monoclonal Gammopathy of Undetermined Significance (MGUS)

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.

(See also Overview of Plasma Cell Disorders.)

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 (1). MGUS may occur in association with other disorders (see table 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.

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%/year) progress to myeloma or a related B-cell disorder, such as macroglobulinemia, amyloidosis, or lymphoma (2). Patients with IgM type disease have a higher risk of developing a serious B-cell lymphoproliferative disorder.

The diagnosis of MGUS is usually suspected when the M-protein is incidentally detected in blood or urine during a routine examination or as part of the evaluation for an unexplained peripheral neuropathy. On laboratory evaluation, M-protein is present in lower levels in serum (< 3 g/dL [< 30 g/L]) or urine (< 200 mg/24 hours) than among patients with multiple myeloma. MGUS is differentiated from malignant plasma cell disorders because M-protein levels are lower, clonal plasma cells in bone marrow are lower, and lytic bone lesions, anemia, and renal dysfunction are absent.

Because of fracture risk, baseline evaluation with a skeletal survey (ie, plain radiographs of the skull, long bones, spine, pelvis, and ribs) and bone densitometry should be done.

No antineoplastic treatment is recommended. However, patients with MGUS and associated bone loss (osteopenia or osteoporosis) may benefit from treatment with intravenous bisphosphonates but less frequently than the monthly treatments usually required to treat patients with multiple myeloma.

Every 6 to 12 months, patients should undergo clinical examination and serum and urine protein electrophoresis to evaluate for disease progression.