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Overview of Plasma Cell Disorders

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

By James R. Berenson, MD, President and Chief Medical Officer, Institute for Myeloma and Bone Cancer Research

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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


(For structural features and classification of the immunoglobulins, see Molecular Components of the Immune System : 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 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.

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

  • Autoimmune damage of organs (particularly the kidneys): Some M-proteins show antibody activity

  • Impaired immunity: Decreased production of other immunoglobulins

  • Bleeding tendency: M-protein may coat platelets, inactivate clotting factors, increase blood viscosity, and cause bleeding by other mechanisms

  • Secondary amyloidosis: M-protein can be deposited within organs

  • 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 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 (sulfonamide, phenytoin, and penicillin), with presumed viral infections, and after heart or transplant surgery.

Classification of Plasma Cell Disorders




Monoclonal gammopathy of undetermined significance*

Asymptomatic, usually nonprogressive

Occurring in apparently healthy people or in those with other conditions

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 disease, Kaposi sarcoma, lichen myxedematosus, liver disorders, myasthenia gravis, pernicious anemia, thyrotoxicosis

Malignant plasma cell disorders

Asymptomatic, progressive

Usually light chains (Bence Jones) only, but occasionally intact immunoglobulin molecules (IgG, IgA, IgM, IgD)

Early multiple myeloma

Symptomatic, progressive

Excess production of IgM

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

Usually light chains (Bence Jones) only, but occasionally intact immunoglobulin molecules (IgG, IgA, IgM, IgD)

Heavy chain diseases

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

*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.

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