Clinical aspects of multiple myeloma and related disorders including amyloidosis.

Multiple myeloma is characterized by the presence of bone pain, weakness, and fatigue. Ninety-eight percent of patients have an M-protein in the serum or urine at the time of diagnosis. Skeletal roentgenograms are abnormal in nearly 80%. Renal insufficiency (creatinine > or = 2 mg/dL) is present in one-fourth. The major causes of renal insufficiency are "myeloma kidney" and hypercalcemia. The diagnosis of multiple myeloma depends upon the presence of more than 10% plasma cells or a plasmacytoma plus an M-protein in the serum or urine or lytic bone lesions. Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. The plasma cell labeling index and the presence of circulating plasma cells in the peripheral blood are helpful in the differential diagnosis. Plasma cell leukemia, osteosclerotic myeloma (POEMS syndrome), and plasmacytomas are discussed. The heavy-chain diseases consist of alpha, gamma, and mu heavy-chain disease. The fibrils of primary amyloidosis consist of kappa or lambda monoclonal light chains. Weakness, fatigue, and weight loss are the most frequent symptoms. Macroglossia occurs in 10%. An M-protein is found in the serum or urine in 90%. The presence of nephrotic syndrome, renal insufficiency, congestive heart failure, orthostatic hypotension, or sensorimotor peripheral neuropathy, and an M-protein in the serum or urine suggest the possibility of primary amyloidosis. The diagnosis depends upon the demonstration of amyloid in tissues. The subcutaneous fat aspirate is positive in 80% while the bone marrow is positive in 55%. If these tissues are negative, one should obtain tissue from an involved organ.