Multiple Myeloma and Other Plasma Cell Neoplasms

Monoclonal expansion of plasma cells and their precursors give rise to a spectrum of plasma cell neoplasms ranging from indolent to aggressive. These include monoclonal gammopathy of undetermined significance (MGUS; 67%), multiple myeloma (14%), solitary plasmacytoma of bone or extraosseous tissue (3%), primary amyloidosis (AA; 9%) and immunoglobulin (Ig) chain deposition diseases (<1%), POEMS (polyneuropathy, organomegaly, endocrinopathy, M component, and skin changes) syndrome, and more recently recognized TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting).The past decade saw remarkable advances in understanding the biology of myeloma and improved patient survival. Virtually all myelomas arise from precursor lesions such as MGUS and smoldering stage through stepwise accumulation of genetic lesions and altered bone marrow microenvironment. Genomic and single cell sequencing have revealed intra-clonal heterogeneity in myeloma and how clonal selection affects therapeutic efficacy. Highly sensitive multicolor flow cytometry immunophenotyping and deep sequencing now afford a more robust measurement of minimal residual diseases than before, allowing more stringent criteria for complete remission. Newer generation and categories of therapeutics have dramatically improved patient survival. These advances have changed the paradigm of the disease model, reshaping the standard of practice in terms of diagnosis and management of patients. This chapter focuses first on an update in myeloma, the prototype of plasma cell neoplasm, and its variants and second with a description of other types of related neoplasms.