Monoclonal gammopathies of undetermined significance: a review

Monoclonal gammopathy of undetermined significance (MGUS) denotes the presence of a monoclonal protein (M-protein) in patients without evidence of multiple myeloma (MM), macroglobulinemia, amyloidosis (AL), or a related plasma cell proliferative disorder. MGUS is found in approximately 3% of persons older than 70 years and in about 1% of those older than 50 years. In a series of 1384 patients from south-eastern Minnesota in whom MGUS was diagnosed at Mayo Clinic from 1960 through 1994, the risk of progression was 1% per year. Patients were at risk of progression even after 25 years or more of a stable monoclonal gammopathy. The risk of development of MM was increased by 25-fold, the risk of macroglobulinemia was 46-fold, and the risk of primary AL was 8.4-fold when compared with a similar population (Surveillance, Epidemiology and End Results). The concentration of the serum M-protein was the major independent predictor of progression. Patients with an immunoglobulin M (IgM) or an IgA monoclonal gammopathy had a higher risk of progression than those with an IgG monoclonal gammopathy. The presence of a urine M-protein or the reduction of one or more uninvolved Igs was not a risk factor for progression. MGUS may be associated with many different disorders, including lymphoproliferative diseases, leukemia, connective tissue disorders, dermatologic diseases, and neurologic disorders.