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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 Sep 2019| Content last modified Sep 2019
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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

(For structural features and classification of the immunoglobulins, see Antibodies.)

After developing in the bone marrow, undifferentiated B cells enter peripheral lymphoid tissues, such as 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.

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.

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

  • Damage to organs (particularly the kidneys due to hypercalcemia or toxic light chains secreted by the malignant plasma cell): Some M-proteins show antibody activity against self-antigens.

  • Impaired immunity: There is decreased production of other immunoglobulins.

  • Bleeding tendency: M-protein may cause bleeding by coating platelets, inactivating clotting factors, increasing blood viscosity, and other mechanisms.

  • Amyloidosis: M-protein can form fibrillar deposits within organs, most commonly the heart and kidney.

  • Osteoporosis, hypercalcemia, anemia, or pancytopenia: Clonal cells can infiltrate bone matrix and/or marrow.

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

Table
icon

Classification of Plasma Cell Disorders

Symptoms

Description

Examples

Monoclonal gammopathy of undetermined significance

Asymptomatic, usually nonprogressive

Occurring in apparently healthy people or in those with other conditions

Associated with B-cell cancers but also nonlymphoreticular tumors

Multiple myeloma, B-cell lymphoma, chronic lymphocytic leukemia or, less commonly, carcinomas of the breasts, biliary tree, gastrointestinal tract, kidneys, and prostate

Associated with chronic inflammatory and infectious conditions

Associated with various other disorders

Familial hypercholesterolemia, Gaucher disease, Kaposi sarcoma, lichen myxedematosus, liver disorders, myasthenia gravis, pernicious anemia, hyperthyroidism

Malignant plasma cell disorders

Asymptomatic, progressive

Usually intact monoclonal immunoglobulin molecules (IgG, IgA, IgM, IgD) with or without monoclonal light chains (Bence Jones proteins) in urine and/or in serum)

Smoldering multiple myeloma

Symptomatic, progressive

Excess production of IgM

Most often IgG, IgA, or light chains (Bence Jones) only

Usually intact immunoglobulin molecules (IgG, IgA, IgM, IgD) with or without monoclonal light chains (Bence Jones proteins) in urine and/or serum)

Heavy chains

IgG heavy chain disease (sometimes benign)

IgD heavy chain disease

Transient plasma cell disorders

Not necessarily symptomatic

Associated with drug hypersensitivity, viral infections, and heart or transplant surgery

Hypersensitivity to sulfonamide, phenytoin, or penicillin

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.

Drugs Mentioned In This Article

Drug Name Select Trade
DILANTIN
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