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- Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells.
- This clonal proliferation in the bone marrow (BM) can cause extensive skeletal destruction with osteolytic lesions and pathologic fractures.
- The malignant plasma cells produce monoclonal protein in the blood and urine.
- MM is also characterized by hypercalcemia, increased susceptibility to infections, renal impairment, and end-organ damage.
- Monoclonal gammopathy of undetermined significance (MGUS) is a common disorder with limited monoclonal plasma cell proliferation that can progress to MM at rate of ~1% per year.
- MGUS can progress to smoldering or asymptomatic MM and eventually to symptomatic MM.
- Synonym(s): plasma cell myeloma; plasma cell leukemia
- Accounts for 1.8% of all cancers and slightly >10% of hematologic malignancies in the United States
- Median age of diagnosis is 66 years.
- Slight male predominance. Blacks about 2 to 3 times more commonly affected than whites; less common in Asians
6 to 7 new cases per 100,000 annually in the United States
In 2015, there were ~124,733 cases in the United States.
Etiology and Pathophysiology
- Clonal proliferation of plasma cells derived from postgerminal center B cells
- Plasma cells undergo multiple chromosomal mutations to progress to MM.
- Genetic damage in developing B lymphocytes at time of isotype switching, transforming normal plasma cells into malignant cells, arising from single clone
- Earliest chromosomal translocations involve immunoglobulin (Ig) heavy chains on chromosome 14q32, with the translocation at t(4;14), t(14;16), t(14;20), and deletion, del(17p) having a poorer prognosis.
- Malignant cells multiply in BM, suppressing normal BM cells and producing large quantities of monoclonal Ig (M) protein.
- Malignant cells stimulate osteoclasts that cause bone resorption and inhibit osteoblasts that form new bone, causing lytic bone lesions.
Rare family clusters; the hyperphosphorylated form of paratarg-7, a protein of unknown significance, is inherited as an autosomal dominant trait in familial cases of MM and MGUS, suggesting a potential pathogenic role.
- Most cases have no known risks associated.
- Older age; immunosuppression; and chemicals like dioxin, herbicides, insecticides, petroleum, heavy metals, plastics, and ionizing radiation increase the risk of MM.
- MGUS stage consistently precedes MM.
Commonly Associated Conditions
Secondary amyloidosis commonly due to MM