Chapter 106. Plasma Cell Disorders (Part 3)

Incidence and Prevalence About 19,900 cases of myeloma were diagnosed in 2007, and 10,790 people died from the disease in the United States. Myeloma increases in incidence with age. The median age at diagnosis is 68 years; it is uncommon under age 40. The yearly incidence is around 4 per 100,000 and remarkably similar throughout the world. Males are more commonly affected than females, and blacks have nearly twice the incidence of whites. Myeloma accounts for ~1% of all malignancies in whites and 2% in blacks; 13% of all hematologic cancers in whites and 33% in blacks.The incidence of...
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Chapter 106. Plasma Cell Disorders (Part 3) Chapter 106. Plasma Cell Disorders (Part 3) Incidence and Prevalence About 19,900 cases of myeloma were diagnosed in 2007, and 10,790people died from the disease in the United States. Myeloma increases in incidencewith age. The median age at diagnosis is 68 years; it is uncommon under age 40.The yearly incidence is around 4 per 100,000 and remarkably similar throughoutthe world. Males are more commonly affected than females, and blacks havenearly twice the incidence of whites. Myeloma accounts for ~1% of allmalignancies in whites and 2% in blacks; 13% of all hematologic cancers inwhites and 33% in blacks. The incidence of myeloma is highest in African-American and Pacificislanders; intermediate in Europeans and North American Caucasians; and lowestin developing countries including Asia. The higher incidence in more developedcountries may result from the combination of a longer life expectancy and morefrequent medical surveillance. Incidence of multiple myeloma in other ethnicgroups including native Hawaiians, female Hispanics, American Indians fromNew Mexico, and Alaskan natives is higher relative to U.S. Caucasians in thesame geographic area. Chinese and Japanese populations have a lower incidencethan Caucasians. Immunoproliferative small intestinal disease with alpha heavychain disease is most prevalent in the Mediterranean area. Despite thesedifferences in prevalence, the characteristics, response to therapy, and prognosis ofmyeloma are similar worldwide. Pathogenesis and Clinical Manifestations (Table 106-1) Multiple myeloma (MM) cells bind via cell-surface adhesionmolecules to bone marrow stromal cells (BMSCs) and extracellular matrix (ECM),which triggers MM cell growth, survival, drug resistance, and migration in thebone marrow milieu (Fig. 106-3). These effects are due both to direct MM cell–BMSC binding and to induction of various cytokines including IL-6, insulin-likegrowth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and stromalcell–derived growth factor (SDF)-1α. Growth, drug resistance, and migration aremediated via Ras/Raf/mitogen-activated protein kinase, PI3-K/Akt, and proteinkinase C signaling cascades, respectively. Figure 106-3 Pathogenesis of multiple myeloma. Multiple myeloma cells interact withbone marrow stromal cells and extracellular matrix proteins via adhesionmolecules, triggering adhesion-mediated signaling as well as cytokine production.This triggers cytokine-mediated signaling that provides growth, survival, and anti-apoptotic effects as well as development of drug resistance. HSP, heparin sulfateproteoglycan. Table 106-1 Clinical Features of Multiple Myeloma Clinical Finding Underlying Cause and Pathogenetic Mechanism Hypercalcemia, Tumor expansion, production of osteoclastosteoporosis, pathologic activating factor by tumor cells, osteoblastfractures, lytic bone lesions, inhibitory factorsbone pain Renal failure Hypercalcemia, light chain deposition, amyloidosis, urate nephropathy, drug toxicity (nonsteroidal anti-inflammatory agents, bisphosphonates), contrast dye Easy fatigue—anemia Bone marrow infiltration, production of inhibitory factors, hemolysis, decreased red cell production, decreased erythropoietin levels Recurrent infections Hypogammaglobulinemia, low CD4 count, decreased neutrophil migration Neurologic symptoms Hyperviscosity, cryoglobulinemia, amyloid deposits, hypercalcemia, nerve compression, anti- neuronal antibody, POEMS syndrome, therapy- related toxicity Nausea and vomiting Renal failure, hypercalcemia Bleeding/clotting Interference with clotting factors, antibodydisorder to clotting factors, amyloid damage of endothelium, platelet dysfunction, antibody coating of platelet, therapy-related hypercoagulable defects Note: POEMS, polyneuropathy, organomegaly, endocrinopathy, multiplemyeloma, and skin changes.