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Overview of Plasma Cell Disorders

(Dysproteinemias; Monoclonal Gammopathies; Paraproteinemias; Plasma Cell Dyscrasias)

By

James R. Berenson

, MD, Institute for Myeloma and Bone Cancer Research

Last full review/revision Oct 2021| Content last modified Nov 2021
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Topic Resources

Plasma cell disorders are a diverse group of disorders of unknown etiology characterized by

  • Disproportionate proliferation of a single clone of B cells

  • Presence of a structurally and electrophoretically homogeneous (monoclonal) immunoglobulin or polypeptide subunit in serum, urine, or both

Pathophysiology

After developing in the bone marrow, undifferentiated B cells enter peripheral lymphoid tissues, such as the lymph nodes, spleen, and gut (eg, Peyer patches). Here, they begin to differentiate into mature cells, each of which can respond to a limited number of antigens. After encountering the appropriate antigen, some B cells undergo clonal proliferation into plasma cells. Each clonal plasma cell line is committed to synthesizing one specific immunoglobulin antibody that consists of 2 identical heavy chains (gamma [γ], mu [μ], alpha [α], delta [δ], or epsilon [ε]) and 2 identical light chains (kappa [κ] or lambda [λ]). A slight excess of light chains is normally produced, and urinary excretion of small amounts of free polyclonal light chains ( 40 mg/24 hours) is normal.

In plasma cell disorders, disproportionate proliferation of one clone results in a corresponding increase in the serum level of its product, the monoclonal immunoglobulin protein (M-protein). M-proteins may consist of both heavy and light chains or of only one type of chain.

Complications of plasma cell proliferation and M-protein production include the following:

Plasma cell disorders can vary from asymptomatic, stable conditions (in which only the monoclonal protein is present) to progressive cancers (eg, multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more Multiple Myeloma —for classification, see table Classification of Plasma Cell Disorders Classification of Plasma Cell Disorders Plasma cell disorders are a diverse group of disorders of unknown etiology characterized by Disproportionate proliferation of a single clone of B cells Presence of a structurally and electrophoretically... read more ). Rarely, transient plasma cell disorders occur in patients with drug hypersensitivity (eg, sulfonamides, phenytoin, penicillin), with presumed viral infections, and after heart or transplant surgery.

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Diagnosis

Plasma cell disorders may be suspected because of clinical manifestations most often bone disease, renal failure, and low blood counts, or an incidental finding of elevated serum protein or proteinuria that leads to further evaluation with serum or urine protein electrophoresis. Electrophoresis often detects an M-protein and/or elevated serum free light chains. These findings are further evaluated with immunofixation electrophoresis for identification of heavy and light chain classes.

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