Description

• 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

Epidemiology

• Accounts for nearly 2% of all cancers and 17% 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

Incidence
4 to 5 new cases per 100,000 annually in the United States

Prevalence
In 2018, there were nearly ~160,000 recognized cases worldwide (1)[A].

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 (2)[C].
• 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.

Genetics
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