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  • Essential monoclonal gammopathy is the presence of a serum monoclonal immunoglobulin (Ig) or a serum and urine monoclonal Ig light chain in the absence of evidence for a B-cell tumor (eg, B-cell lymphoma, macroglobulinemia, myeloma, plasmacytoma, amyloidosis) over a period of observation.

  • The monoclonal Ig may be of any isotype and may occasionally be of multiple isotypes (Table 68–1).

  • Synonyms for essential monoclonal gammopathy include (1) monoclonal gammopathy; (2) benign monoclonal gammopathy; and (3) monoclonal gammopathy of unknown significance (MGUS). The latter seems less appropriate now that the significance of this diagnosis is precisely known, and it is one of many examples of stable clonal disorders with a predisposition to undergo clonal evolution to a malignant disorder (eg, adenomatous colonic polyp), making its significance apparent. In keeping with modern terminology, monoclonal gammopathy of indeterminate progression (M-GIP) would be more appropriate for the aficionados of acronyms.

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Serum IgG, IgA, IgM, IgE, IgD
Serum IgG + IgA, IgG + IgM, IgG + IgA + IgM
Serum monoclonal κ or λ light chain

aUrinary monoclonal immunoglobulin (Ig) light-chain excretion (Bence Jones proteinuria) may accompany the presence of serum monoclonal light chain.


  • Essential monoclonal gammopathy may occur at any age, but it is very unusual before puberty and increases in frequency with age. Frequency is approximately 1% in those over 25 years, 3% in those over 70 years, and 10% in those over 80 years of age based on zonal electrophoresis studies.

  • Frequency is higher with more sensitive immunologic techniques (eg, isoelectric focusing or immunoblotting).

  • Frequency is significantly greater among Americans of African descent than those of European descent in comparative age groups.

  • Frequency is greater in males than females.

  • Familial aggregation of persons with essential monoclonal gammopathy occurs.

  • Essential monoclonal gammopathy may harbinger the future development of a B-cell neoplasm (eg, myeloma). Most, and perhaps all, patients with myeloma evolve from a preceding essential monoclonal gammopathy.


  • The gammopathy results from the growth of a single mutated B lymphocyte into a clone of cells that produce a monoclonal Ig and or monoclonal light chains. Cessation of expansion of the clone occurs, and the size of the clone remains stable, at a steady-state of approximately 1 to 5 × 1010 cells, indefinitely.

  • At this clone size, organ pathology such as osteolysis, hypercalcemia, renal disease, or hematopoietic suppression does not occur. Polyclonal Ig synthesis is usually normal, and thus, increased frequency of infections is not a feature.

  • IgA and IgG monoclonal gammopathies arise from a somatically mutated postswitch preplasma cell, and IgM monoclonal gammopathy arises from a mutated germinal center B lymphocyte without evidence of isotype switching. This feature influences the result of clonal progression: IgA and ...

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