Multiple Myeloma and Other Plasma Cell Neoplasms

Monoclonal expansion of plasma cells and their precursors gives rise to a spectrum of plasma cell neoplasms (PCNs) ranging from indolent to aggressive. The indolent diseases such as monoclonal gammopathy of undetermined significance (MGUS), which constitutes a vast majority of cases of PCNs, are usually diagnosed incidentally, while the most aggressive forms such as advanced stage (or refractory) multiple myeloma or plasma cell leukemia are associated with significant mortality and morbidity. Complications of abnormal proteins produced by the neoplastic cells include immunoglobulin (Ig)-related amyloidosis or Ig deposition diseases, as well as several paraneoplastic syndromes which can be more debilitating than the direct infiltrate of neoplastic cells. Virtually all myelomas arise from precursor lesions such as MGUS, through accumulation of genetic lesions and an altered tumor microenvironment. Genomics, including single-cell sequencing and proteomics, have revealed intra-clonal heterogeneity in myeloma and how clonal evolution and selection affect therapeutic efficacy. Highly sensitive multicolor flow cytometry immunophenotyping and deep sequencing allow more robust measurement of residual disease than before, redefining criteria for complete remission. Novel therapies have drastically improved patient outcomes. These advances have changed the paradigm of the disease model, reshaping the standard of practice and survival outlook. This chapter focuses first on an update in myeloma, the prototype of PCN, and its variants, followed by a description of other types of related neoplasms. The fifth edition WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues and International Consensus Classification are both referenced, and their differences are specified.