Chapter 67: Essential Monoclonal Gammopathy

DEFINITION

• Essential monoclonal gammopathy is 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 (eg, 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 67–1).

• Synonyms for essential monoclonal gammopathy include (1) monoclonal gammopathy; (2) benign monoclonal gammopathy; and (3) 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 (eg, adenomatous colonic polyp), making its significance apparent.

EPIDEMIOLOGY

• Essential monoclonal gammopathy may occur at any age, but it is very unusual before puberty and increases in frequency with age. Frequency approximately is 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.

ETIOLOGY AND PATHOGENESIS

• The gammopathy results from the growth of a single mutated 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 and IgG monoclonal gammopathy 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 ...