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Multiple Myeloma

Multiple Myeloma is a topic covered in the 5-Minute Clinical Consult.

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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 progresses to MM at rate of ~1% per year.
  • MGUS progresses to smouldering or asymptomatic MM and eventually to symptomatic MM.
  • Synonym(s): plasma cell myeloma; plasma cell leukemia


  • Accounts for ~1% 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

4 to 5 new cases/100,000 annually

In 2012, there were 89, 658 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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Stephens, Mark B., et al., editors. "Multiple Myeloma." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116392/all/Multiple_Myeloma.
Multiple Myeloma. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116392/all/Multiple_Myeloma. Accessed April 24, 2019.
Multiple Myeloma. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116392/all/Multiple_Myeloma
Multiple Myeloma [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 24]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116392/all/Multiple_Myeloma.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Multiple Myeloma ID - 116392 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116392/all/Multiple_Myeloma PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -