Multiple Myeloma

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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.

Risk Factors

  • 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

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