Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a monoclonal protein (M-protein) without evidence of multiple myeloma (MM), Waldenström's macroglobulinemia (WM), amyloidosis (AL), or a related plasma cell proliferative disorder. Agarose gel electrophoresis followed by immunofixation is recommended for recognition of an M-protein. Monoclonal gammopathy of undetermined significance is found in approximately 3% of persons > 70 years of age and in about 1% of those > 50 years old. In a series of 1384 patients from Southeastern Minnesota in whom MGUS was diagnosed at Mayo Clinic from 1960 through 1994, the risk of progression was 1% per year. This risk of progression continued even after ≥ 25 years of a stable M-protein. The risk for developing MM, WM, or AL was increased 25-fold, 46-fold, and 8.4-fold, respectively. The concentration of the serum M-protein, abnormal serum free lightchain ratio, and the presence an immunoglobulin (Ig)M or an IgA M-protein were risk factors for progression. The presence of a urine M-protein or the reduction of ≥ 1 uninvolved immunoglobulins was not a risk factor for diease progression. Patients must be monitored for progressive disease throughout their lives. Variants of MGUS consist of IgM MGUS, biclonal gammopathies, triclonal gammopathies, idiopathic Bence Jones (light-chain) proteinuria, and IgD MGUS. Monoclonal gammopathy of undetermined significance may be associated with many disorders, including lymphoproliferative diseases, leukemia, von Willebrand's disease, connective tissue diseases, and neurologic disorders. Epidemiologic and statistical methods must be used to evaluate these associations.