ABSTRACT
Plasma cell neoplasms are distinguished by an idiotypic rearrangement of the immunoglobulin gene, which occurs prior to the malignant transformation of an early plasma cell precursor. The clone that develops must increase to about 5 109 cells before it produces enough of the idiotypic immunoglobulin to be recognized as a monoclonal ‘spike’ (M-protein or paraprotein) in a serum electrophoresis pattern. Most subjects with a serum M-protein are asymptomatic; if other causes of an M-protein can be ruled out, they are labeled as monoclonal gammopathies of undetermined significance (MGUS). By definition, the monoclone in MGUS is stable and the serum M-protein concentration remains level for many years. However, prolonged follow-up of a large group of MGUS subjects at the Mayo Clinic has shown that about 2% of these patients progress per year to develop symptomatic multiple myeloma (MM), macroglobulinemia, malignant lymphoma, chronic lymphocytic leukemia or amyloidosis (Chapter 24).1 MGUS is considered to be a premalignant lesion because the clone does not grow progressively but is stable and asymptomatic. Almost all of the genetic aberrations identified in MM (aneuploidy, monosomy 13, 14q32 chromosome translocations) are also present in MGUS.2 Additional neoplastic changes are required to convert this large stable clone into MM, a progressively expanding tumor with malignant characteristics.
