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The term 'benign monoclonal gammopathy' indicates the presence of a monoclonal protein in persons without evidence of multiple myeloma, macroglobulinaemia, amyloidosis, lymphoproliferative disease, or other related disorders. The term 'monoclonal gammopathy of undetermined significance' (MGUS) is preferable because it is not known at diagnosis whether an M-protein will remain stable and benign or develop into symptomatic multiple myeloma or related disorders. Immunoelectrophoresis and immunofixation of the serum and urine are necessary to determine the presence and type of M-protein. At the Mayo Clinic, follow-up data have been gathered for more than 13 years on 241 patients with an initial benign monoclonal gammopathy. Nineteen per cent of these patients developed multiple myeloma, macroglobulinaemia, amyloidosis, or related diseases during the follow-up period. There is no reliable technique for differentiating a patient with a benign monoclonal gammopathy from one who will subsequently develop a serious disease. It is necessary to follow these patients indefinitely. Important in the complete understanding of the elderly patient with monoclonal gammopathy are the following: clinical manifestations, laboratory findings, and differential diagnosis of multiple myeloma; the course and prognosis and the induction therapy and treatment of multiple myeloma; newer therapeutic approaches; and the management of complications such as hypercalcaemia, hyperuricaemia, renal failure, bacterial infections, skeletal disease, and neurological problems.

Morphological characteristics of tumor cells have been employed in the prognosis of lymphomas and solid tumors. This report documents an attempt to predict survival from the known cytologic heterogeneity in multiple myeloma. Myeloma cells in bone marrow smears from patients at diagnosis were evaluated by assigning them to morphologically defined categories. Cox's multivariate regression model for censored survival data was used to generate optimal weights, which served as coefficients in two regression equations to estimate death risk from cellular morphology. Step-wise procedures excluded redundant parameters. "Myeloma morphology score" (MMS) discriminates significantly (p less than 0.0001) among 3 stages, with median survival times of 42.5, 30.7, and 9.1 mo. For clinical routine application, "myeloma progression score" (MPS), the weight sum of the proportion of plasmablasts and the extent of bone marrow plasma cell infiltration, is suggested as a simple prognostic tool. Its discriminative power is very high [p less than 10(-9)]. Median survival times of greater than 71.5, 23.4, and 6.1 mo were found for good, moderate, and poor risk groups, respectively. However, staging is not confined to three subgroups, grouping is flexible, and pairs of data can be matched. This fact may prove to be valuable in designing prognosis-controlled clinical trials or theoretical studies on cellular differentiation. Preliminary results suggest changes in morphology due to disease progression and/or the effect of therapy on tumor kinetics. Most importantly, staging according to MPS or MMS may facilitate the adaption of therapy to the current state of the disease in patients with multiple myeloma.

The demonstration of monoclonal, homogeneous immunoglobulin or its subunit is the hallmark of plasma-cell dyscrasia. Plasma-cell dyscrasia can be classified into two main groups: "primary" and "secondary". The increasing use of protein electrophoresis and immunoelectrophoresis has contributed to the increased frequency of secondary monoclonal gammopathy and to the better recognition of its clinical significance. Secondary monoclonal gammopathy usually stems from the reactive unbalanced proliferation of B cells resulting from chronic inflammatory diseases or from other malignancies. Only in some cases its cause is difficult to assert. A case of secondary plasma-cell dyscrasia of undetermined cause is presented. The patient had IgG kappa monoclonal gammopathy of 3580 mg/dl, and multiple osteolytic bone lesions. However the histopathological picture showed a chronic inflammatory process, and the diagnosis of multiple myeloma could not be established. The diagnostic problems in this case are discussed, with the recommendation that more strict and accurate immunochemical terms concerning monoclonal gammopathy be used.

This study evaluated the utility of the immunoperoxidase method as applied to bone marrow sections in the diagnosis of patients with monoclonal gammopathies. Intracellular immunoglobulin light chains were identified in fixed, decalcified bone marrow biopsy sections from 66 patients with monoclonal proteins, using an avidin-biotin-peroxidase complex immunoperoxidase method. In all cases the predominant light chain identified in the bone marrow biopsy correlated with the monoclonal light chain identified in the serum. In addition, a light chain ratio was defined that correlated with the clinical diagnoses. The light chain ratios were highest in patients with multiple myeloma and were significantly different from those with monoclonal gammopathy of undetermined significance. There was no correlation between level of serum monoclonal protein and light chain ratios. The ratios were also high in patients with macroglobulinemia, primary amyloidosis, and renal disease secondary to monoclonal proteins but without overt myeloma. Determination of light chain ratios differentiated patients with multiple myeloma from those with monoclonal gammopathy of undetermined significance and helped identify patients with end organ damage secondary to monoclonal proteins but without overt myeloma.