Plasma cell disorders are a diverse group of disorders of unknown etiology characterized by the disproportionate proliferation of one clone of B cells and the presence of a structurally and electrophoretically homogeneous (monoclonal) immunoglobulin or polypeptide subunit in serum, urine, or both.

Pathophysiology

(For structural features and classification of the immunoglobulins, see Biology of the Immune System: Antibodies.)

After developing in the bone marrow, undifferentiated B cells enter peripheral lymphoid tissues, such as lymph nodes, spleen, gut, and Peyer's patches. Here, they begin to differentiate into 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 h) is normal.

Plasma cell disorders are of unknown etiology and are characterized by the disproportionate proliferation of one clone. The result is 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. Some show antibody activity, which may cause autoimmune damage of organs, particularly the kidneys. When M-proteins are produced, production of other immunoglobulins is commonly reduced, and immunity may become impaired. M-protein may coat platelets, inactivate clotting factors, increase blood viscosity, and cause bleeding by other mechanisms. M-proteins may also produce secondary amyloidosis. The clonal cells can infiltrate bone matrix or marrow, with resultant osteoporosis, hypercalcemia, anemia, or pancytopenia.

Plasma cell disorders can vary from asymptomatic, stable conditions (in which only the protein is present) to progressive cancers (eg, multiple myeloma—for classification, see Table 1: Plasma Cell Disorders: Classification of Plasma Cell Disorders). Rarely, transient plasma cell disorders occur in patients with drug hypersensitivity (sulfonamide, phenytoin, and penicillin), with presumed viral infections, and after heart or transplant surgery.

Table 1
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Classification of Plasma Cell Disorders Symptoms Description Examples Monoclonal gammopathy of undetermined significance* Asymptomatic, usually nonprogressive Occurring in apparently healthy people Associated with nonlymphoreticular tumors Carcinomas of the breasts, biliary tree, GI tract, kidneys, and prostate Associated with chronic inflammatory and infectious conditions Chronic cholecystitis, osteomyelitis, pyelonephritis, RA, TB Associated with various other disorders Familial hypercholesterolemia, Gaucher's disease, Kaposi's sarcoma, lichen myxedematosus, liver disorder, myasthenia gravis, pernicious anemia, thyrotoxicosis Malignant plasma cell disorders Symptomatic, progressive Excess production of IgM Macroglobulinemia Most often IgG, IgA, or light chains (Bence Jones) only Multiple myeloma Usually light chains (Bence Jones) only, but occasionally intact immunoglobulin molecules (IgG, IgA, IgM, IgD) Nonhereditary primary systemic amyloidosis Heavy chain diseases IgG heavy chain (γ-chain) disease (sometimes benign) IgA heavy chain (α-chain) disease IgM heavy chain (μ-chain) disease IgD heavy chain (δ-chain) disease Transient plasma cell disorders — Associated with drug hypersensitivity, viral infections, and heart or transplant surgery Hypersensitivity to sulfonamide, phenytoin, or penicillin *Age-related incidence.

Plasma cell disorders may be suspected because of clinical manifestations, findings during evaluation of anemia, or an incidental finding of elevated serum protein or proteinuria that leads to further evaluation with serum or urine protein electrophoresis. Electrophoresis detects M-protein, which is further evaluated with immunofixation electrophoresis for identification of heavy and light chain classes.

Last full review/revision July 2008 by James R. Berenson, MD