Germline Abnormalities

Monoclonal gammopathy is an uncommon finding, accounting for 1.2% of randomly selected hospitalized patients, 3% in patients older than 70 years and 10% of patients over 80 years. Significance is determined by the magnitude of serum monoclonal protein and associated findings of M-protein in the urine, lytic lesions, anemia, hypercalcemia, renal failure and disease progression. Bernett reported a retrospective study of 534 cases in which the referring diagnosis was plasmacytoma. Twenty-two patients lacked associated findings of a neoplasm and over a 10-year period 36% converted to a malignancy [14]. Kyle [15] reported a larger series of 13,022 patients with monoclonal gam-mopathies. Approximately 62% of the patients with dysproteinemia had monoclonal gammopathies of undetermined significance and solitary plasmacytoma. The significant disease associations with paraproteinemias were, in decreasing order, multiple myeloma (MM), amyloidosis, lymphoproliferative disease, solitary or extramedullary plasmocytoma, Waldenstrom's macroglobulinemia, lymphoma and chronic lymphocytic leukemia. Approximately 15-20% of the M-proteins were of the IgM type. Long-term (>20 year) follow-up of monoclonal gammopathy of undetermined significance in 241 patients revealed the heavy-chain type to be IgG 73%, IgM 14%, IgA

11% and biclonal 2%. In this group of patients the etiology for 75% of the cases was related to nonneoplastic inflammatory conditions. However, in 26% of patients multiple myeloma, macroglobulinemia, amyloidosis or a malignant lymphoproliferative disorder developed.

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