Multiple Myeloma

Description

• Multiple myeloma (MM) is a malignant proliferation of a single clone of plasma cells. These malignant cells produce monoclonal protein (immunoglobulin [Ig]) that can be detected in the blood and/or urine as it is filtered in the kidneys.
• MM is characterized by bony lytic lesions, hypercalcemia, increased susceptibility to infections, and renal impairment.
• Monoclonal gammopathy of undetermined significance (MGUS) is a common disorder with limited monoclonal plasma cell proliferation that can progress to smoldering MM or symptomatic MM at rate of ~1% per year.

Epidemiology

• Median age: 65 to 74 years.
• ~2% of all cancers and 17% of hematologic malignancies in the United States
• African Americans about 2 to 3 times more commonly affected than Caucasians; less common in Asians

Etiology and Pathophysiology

• Arises from uncontrolled growth of a single clone of plasma cells in the bone marrow (BM), leading to an excessive production of abnormal monoclonal Ig, also called M proteins.
• Chromosomal translocations involving the Ig heavy chain loci, like t(11;14), t(4;14), or mutations in oncogenes or tumor suppressor genes, contribute to tumorigenesis and disease progression.
• The malignant plasma cells interact with the bone marrow stroma, inhibiting osteoblast function and stimulating osteoclast activity, which results in bone destruction, lytic lesions, and hypercalcemia that are commonly seen in patients with MM.

Risk Factors

• Most cases have no known risks associated.
• Old age; immunosuppression; and exposure to chemicals, heavy metals, and ionizing radiation increase the risk of MM

Commonly Associated Conditions

Secondary amyloidosis with MM and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS).