Monoclonal gammopathies of clinical significance

Abstract

"Monoclonal gammopathy of clinical significance" (MGCS) is the term used to describe nonmalignant monoclonal gammopathies causing important disease. MGCS is the differential diagnosis for any patient presenting with what appears to be a monoclonal gammopathy of undetermined significance but is also experiencing other unexplained symptoms. Broadly, these conditions can be separated into symptoms and signs referable to the nerves, the kidneys, and the skin. The first step in making these diagnoses is to consider them. With a particular condition in mind, the next step is to order those tests that can help confirm or dismiss a particular diagnosis. Nearly all of the renal and dermatologic conditions are diagnosed by renal and skin biopsies, respectively. The importance of a highly competent renal pathologist and dermatopathologist cannot be underestimated. Biopsy is less specific for the neuropathic conditions. Because several of the MGCSs are syndromes, recognizing other manifestations is also key. Treatment recommendations for many of these conditions are anecdotal because of their rarity, but for several of the conditions, IV immunoglobulin, rituximab, and plasma cell-directed therapy are the best options.

Graphical abstract

Figure 1.

Part of the monoclonal gammopathy of clinical significance spectrum. (A) Bone marrow plasma cells (original magnification, 100×). (B) Osteosclerotic lesions of POEMS syndrome (polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes). (C) Schnitzler syndrome. (D and E) Scleromyxedema. (F) Necrobiotic xanthogranuloma. (G) Cryoglobulinemia vasculitis.

Figure 2.

Monoclonal gammopathy of clinical significance and organ system involvement. CANOMAD, chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M paraprotein, cold agglutinins, and disialosyl antibodies; DADS-M-PN, distal acquired demyelinating symmetric neuropathy with M protein; GN, glomerulonephritis; LC, light chain; NXG, necrobiotic xanthogranuloma; PGMID, proliferative glomerulonephritis with monoclonal immune deposition; POEMS, polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes.