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

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

  • Synonyms for essential monoclonal gammopathy include (a) monoclonal gammopathy, (b) benign monoclonal gammopathy, (c) monoclonal gammopathy of unknown significance, with the acronym MGUS. The latter seems less appropriate now that the significance of this diagnosis is precisely known, and it is one of many examples of nonprogressive, clonal disorders with a predisposition to undergo clonal evolution to a malignant disorder (e.g., adenomatous colonic polyp).



  • May occur at any age but very unusual before puberty and increases in frequency with age. Frequency approximately 1 percent in those over 25 years, 3 percent in those over 70 years, and 10 percent in those over 80 years of age based on zonal electropheresis studies.

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

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

  • Frequency 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, notably myeloma. A large proportion of patients with myeloma evolve from a preceding essential monoclonal gammopathy.


  • Result from the growth of single B-lymphocyte into a clone of cells that elaborate a monoclonal immunoglobulin 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 immunoglobulin synthesis is usually normal and, thus, increased frequency of infections is not a feature.

  • IgA or IgG monoclonal gammopathy arise from a somatically mutated post-switch pre-plasma 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 IgG monoclonal gammopathy tends to evolve into myeloma or amyloidosis and IgM monoclonal gammopathy tends to progress to lymphoma or macroglobulinemia.

  • The monoclonal immunoglobulin may react against self-antigen(s), resulting in symptomatic disease (e.g., neuropathy) that depends on the self-antigen ...

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