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Chapter 30. The Lymphoid System: III. Plasma Cell Neoplasms; Spleen & Thymus

Monoclonal Gammopathy

As described elsewhere (Chapter 29: The Lymphoid System: II. Malignant Lymphomas), neoplastic proliferations of B lymphocytes are demonstrably monoclonal; if plasmacytoid differentiation occurs, the neoplastic cells may secrete immunoglobulin that will accumulate in the serum and produce a monoclonal spike on electrophoresis, or M protein. The terms monoclonal gammopathy and plasma cell dyscrasia are employed synonymously for disorders in which a monoclonal spike is present in serum. Most conditions associated with monoclonal gammopathy (Table 30-1) show evidence of proliferation of plasma cells or plasmacytoid cells—hence the term plasma cell dyscrasia. It is important to distinguish the forms of monoclonal gammopathy that are malignant because they require treatment.

Table 30–1. Causes of Monoclonal Gammopathy*.
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Table 30–1. Causes of Monoclonal Gammopathy*.
Monoclonal Spike
Neoplastic
Multiple myeloma Multiple plasma cell neoplasms in bone IgG, IgA, IgM, IgD, or free light chains
Plasmacytoid lymphocytic lymphoma 1 Lymph node or tissue mass containing neoplastic plasmacytoid lymphocytes Usually IgM (macroglobulinemia)
Alpha heavy chain disease 2 Plasmacytoid cell neoplasm especially involving gut wall Alpha chain only
Amyloidosis Usually associated with an underlying plasmacytic neoplasm IgG or light chain
Nonneoplastic
Benign monoclonal gammopathy Mild reactive plasmacytosis in marrow: by definition not malignant 3 Usually low–level stable IgG
Transient gammopathies Probably a phase of florid immune response when one clonal product (antibody type) dominates; seen in some infections and with some cancers Usually IgG, low–level
Autoimmune gammopathy Monoclonal immunoglobulins are found as part of mixed cryoglobulinemia and cold agglutinin disease (see text); rare Usually IgM, low–level

*ie, the presence of a monoclonal or M spike in serum.

1 Other B cell neoplasms (chronic lymphocytic leukemia follicular center cell lymphomas and immunoblastic sarcoma of B cell type) may also produce detectable spikes if very sensitive techniques are utilized.

2 Gamma and mu chain diseases also occur but are very rare (see text).

3 It is not known whether the condition represents a benign neoplasm or a reactive clone that becomes predominant and persists.

Diagnosis

Serum Protein Electrophoresis

The serum contains numerous proteins that may be separated by electrophoresis according to differences in size and charge. Protein molecules are allowed to migrate on special paper or in a gel under the influence of an electrical field. Identical molecules migrate to an identical point within the field, and each different protein accumulates at a characteristic point under specified conditions (Figure 30-1). Protein accumulations, or bands, may be visualized by staining and quantitated by densitometry: The higher the density of the band, the more protein is present.

Figure 30–1.
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Serum protein electrophoresis. In normal individuals, all molecules of albumin are identical in charge and molecular weight and therefore accumulate in one narrow band on electrophoresis. Because the serum contains ...

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