Definition:
Multiple myeloma is a malignant neoplasm of plasma cells in the bone marrow, characterized by the clonal proliferation of abnormal plasma cells that produce monoclonal immunoglobulin (also called paraprotein), most commonly IgG or IgA, and rarely IgM or IgD.
Etiology:
- Exact cause unknown
- Associated risk factors:
- Advanced age (>60 years)
- Male sex
- African descent
- Prior exposure to radiation or carcinogens (e.g., benzene)
- Monoclonal gammopathy of undetermined significance (MGUS) can progress to MM
- Genetic alterations: chromosome 13 deletion, translocations involving IgH locus on 14q32
Pathogenesis & Symptoms:
1. Bone Destruction:
- Osteolytic lesions due to activation of osteoclasts and inhibition of osteoblasts
- Bone resorption → fractures (especially spine, skull, ribs, pelvis, long bones)
- Hypercalcemia from bone breakdown → fatigue, constipation, confusion
- Symptoms: Bone pain, especially in back and ribs; fractures
2. Bone Marrow Infiltration:
- Malignant plasma cells crowd out normal hematopoietic cells →
- Anemia (fatigue, pallor)
- Neutropenia (infections)
- Thrombocytopenia (bleeding risk)
- Paraprotein in blood → hyperviscosity syndrome (rare): headache, blurred vision, bleeding
3. Renal Impairment:
- Due to:
- Light chain cast nephropathy (Bence Jones proteins)
- Hypercalcemia
- Hyperuricemia
- NSAID use
- Amyloidosis (rarely)
- Results in renal failure (common in MM)
4. Immune Suppression:
- Immunoparesis: suppression of normal immunoglobulin synthesis
- Recurrent infections, especially respiratory tract