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SUMMARY
Plasma cell neoplasms are tumors derived from an expansion of mutated mature B-cells and their precursors. These neoplasms include essential monoclonal gammopathy (synonym: monoclonal gammopathy of unknown significance; Chap. 17), smoldering myeloma (Chap. 18), myeloma (Chap. 18), solitary and extramedullary plasmacytomas (Chap. 18), light-chain amyloidosis (Chap. 19), and Waldenström macroglobulinemia (Chap. 20). The prototype of a malignant plasma cell neoplasm is myeloma, which is characterized by complex genetic alterations, best assessed by metaphase cytogenetics, fluorescence in situ hybridization analysis, and gene-expression profiling. The genetic changes are more akin to solid tumors than to hematologic malignancies. Interactions between myeloma cells and the marrow microenvironment affect the survival, proliferation, and drug resistance of myeloma cells and the development of osteoporosis or osteolysis, which is a hallmark of myeloma. As in most malignancies, a cancer stem cell (e.g., myeloma stem cell) has been identified and is the most likely site of drug resistance, which almost invariably develops during treatment; such cells are not affected by the typical drugs one uses in patients with myeloma. The best prognostic markers in myeloma in order of importance are the presence of (1) specific cytogenetic abnormalities, (2) extent of the disease by appropriate imaging techniques, such as magnetic resonance imaging and/or combined positron emission and computed tomographic imaging, (3) the serum-free light-chain level and kappa-to-lambda ratio, and (4) the use of the International Staging System. The development of several classes of drugs over the past decade in combination with transplantation has improved therapeutic outcomes significantly in patients achieving an unequivocal complete remission. Thus, optimal techniques to assess minimal residual disease have also become important.
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DEFINITION AND HISTORY
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Plasma cell neoplasms (PCNs) are clonal B-cell tumors that range from stable disease without functional abnormalities (monoclonal gammopathy, synonym monoclonal gammopathy of unknown significance) to one of slowly proliferating plasma cells (smoldering myeloma [SMM]), to one resulting in end-organ compromise (myeloma). PCNs are accompanied by the synthesis and release into the plasma of a monoclonal (M) protein and, in the case of myeloma, either diffuse osteoporosis or osteolytic lesions. Myeloma accounts for approximately 1 percent of all malignant diseases and 10 percent of hematologic malignancies.
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Approximately two-thirds of patients presenting with an M protein have (1) monoclonal gammopathy (Chap. 17), whereas approximately 15 percent have (2) myeloma (Chap. 18). Other diseases associated with M-protein productions are (3) immunoglobulin light-chain amyloidosis (AL) (10 percent; Chap. 19) resulting from the deposition of immunoglobulin (Ig) fragments in visceral organs as a consequence of extensive misfolding of these Ig fragments; (4) SMM (3 percent; Chap. 18); (5) Waldenström macroglobulinemia (3 percent; Chap. 20); (6) lymphoproliferative disorders (2 percent; Chap. 1); (7) solitary or extramedullary plasmacytomas (1 percent; Chap. 18); and (8) miscellaneous other diseases (2 percent).1
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Acronyms and Abbreviations:...