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INTRODUCTION

SUMMARY

Essential monoclonal gammopathy is defined by two key features: (1) the presence of a monoclonal immunoglobulin or a monoclonal immunoglobulin light chain in the serum and (2) the absence of evidence for an overt malignancy of B lymphocytes or plasma cells (e.g., lymphoma, myeloma, or amyloidosis). The prevalence of essential monoclonal gammopathy depends on the demographic features in the population under study. In Americans of European descent, the prevalence increases from approximately 2 percent in individuals 50 years of age to approximately 7 percent in octogenarians. It is two to three times as prevalent in persons of African descent. The condition has been reported in association with a large variety of disorders, especially nonlymphocytic cancers. These coincidences are thought, in most cases, to be the chance concurrence of conditions that have a high prevalence in older persons. Some cases of essential monoclonal gammopathy are symptomatic because in those cases the immunoglobulin can interact with plasma proteins, blood cells, kidney, ocular structures, or neural tissue and cause serious dysfunction, for example, an acquired bleeding disorder, renal insufficiency, or an incapacitating neuropathy. In such cases, disability may be so great that attempts to remove the immunoglobulin by plasmapheresis and to suppress its production using immune or cytotoxic therapy can be warranted. Because myeloma or lymphoma may emerge at the time the monoclonal immunoglobulin is first detected, periodic evaluation of the patient is required to ascertain if essential monoclonal gammopathy is the appropriate diagnosis. Long-term followup at appropriate intervals is prudent to detect conversion from a stable, asymptomatic condition to a progressive lymphoma or myeloma, which occurs in approximately 0.5 to 1.0 percent of cases per year. In the absence of a symptomatic gammopathy or evolution to a progressive clonal gammopathy, periodic followup is all that is required.

Acronyms and Abbreviations

CD, cluster of differentiation; HLA, human leukocyte antigen; Ig, immunoglobulin; IL, interleukin.

DEFINITION AND HISTORY

The syndrome of essential monoclonal gammopathy has two important characteristics. The first feature is a plasma immunoglobulin (Ig) or Ig light chain that has the molecular features of the product of a single clone of B lymphocytes or plasma cells: homogeneous electrophoretic migration and a single light-chain type. The second feature is the absence of evidence of an overt neoplastic disorder of B lymphocytes or plasma cells, such as lymphoma, myeloma, macroglobulinemia, or amyloidosis.

The observations that Bence Jones proteinuria could precede the clinical signs of multiple myeloma by many years1 and that hyperglobulinemia without evidence of multiple myeloma could occur in some patients2 antedated the concept of monoclonal gammopathy as a syndrome. With the more frequent clinical application of zonal electrophoresis of plasma proteins during the 1950s and 1960s, patients were discovered who had a monoclonal Ig, either without an associated disease or with diseases such as nonlymphoid cancers, infections, and inflammatory disorders, which typically are not associated with a ...

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