Dangerous small B-cell clones.

The detection of a monoclonal immunoglobulin in serum or urine usually raises concerns about the size of the underlying B-cell-derived clone and possible systemic effects caused by its expansion. However, a small clone can synthesize a very toxic protein, producing devastating systemic damage and protean clinical presentations. The resulting "monoclonal component-related diseases," although difficult to diagnose, may be progressive and even fatal. The monoclonal protein can aggregate and deposit systemically as occurs in light-chain amyloidosis, monoclonal immunoglobulin deposition disease, crystal-storing histiocytosis, and monoclonal cryoglobulinemia. Alternatively, some monoclonal proteins possess antibody activity toward autogenous antigens and cause chronic cold agglutinin disease, mixed cryoglobulinemia, and peripheral neuropathies. Other humoral mediators may contribute to neuropathy in variant disorders such as the POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. The clone synthesizing the noxious monoclonal proteins is often small, and sensitive techniques may be required to detect these immunoglobulins. A delay in diagnosis can allow irreversible organ damage and dramatically shorten survival. Prompt recognition of suggestive signs and symptoms should trigger a thorough diagnostic approach to reach the correct diagnosis quickly, because this is the key to effective therapy. Although the treatment of these conditions is not optimal, significant advances have been made, improving the duration and quality of life.