Multiple Myeloma

Summary

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Key Points

• Multiple Myeloma
  • Cause
    • Malignancy of plasma cells
      • Leads to overproduction of IgG (50% of cases) or IgA (20% of cases)
  • Presentation
    • Usually affects older adults (~70 years)
    • Mnemonic: CRAB
      • Calcium, Renal, Anemia, Bone
    • Anemia
      • Plasma cell overgrowth in bone marrow crowds out normal hematopoiesis
      • Normocytic, normochromic anemia (no change in iron or globin, but less production)
      • Usually presents with pallor and fatigue
    • Bone lytic lesions
      • Cytokine production (IL-1 and IL-6) activates RANK receptor on osteoclasts, leading to bone resorption
      • Appears as “punched out” appearance on X-ray
      • May manifest as back pain
    • Hypercalcemia
      • Calcium is released from osteolytic bone lesions
    • Renal failure
      • Elevated BUN and creatinine
      • Due to infiltration by malignant plasma cells, deposition of AL amyloid, and light chain cast nephropathy (Ig light chain deposition) and hypercalcemia (calcification of kidney)
    • Immunosuppression
      • Malignant plasma cells produce monoclonal antibodies that do not have any antigenic diversity (do not protect against various threats)
      • Patients may present with frequent infections
    • Primary amyloidosis (AL)
      • Ig light chain aggregates to produce AL amyloid, which can deposit in various tissues
      • Renal biopsy may show apple-green birefringence on Congo red stain
  • Diagnosis
    • Rouleaux formation on peripheral blood smear
      • RBCs stacked like “poker chips” or “coin pile”
    • M-spike in serum
      • Detected via serum protein electrophoresis (SPEP)
      • Represents overproduction of monoclonal Ig fragment
    • Bence-Jones protein in urine
      • Ig light chain accumulation is known as Bence-Jones protein
      • Detected via 24-hour urine collection and protein electrophoresis
      • Note: rapid urine dipstick is negative (only detects albumin)
    • >10% monoclonal plasma cells on bone marrow biopsy
      • “Clock face” (or “wagon wheel”) chromatin (see: Plasma Cells)
      • Intracytoplasmic inclusions containing IgG
      • Confirms bone marrow infiltration of malignant cells
  • Treatment
    • Chemotherapy
      • Optimal treatment regimen still area of active research
      • Proteasome inhibitors (e.g. bortezomib) may be particularly potent due to high protein production by plasma cells
      • Rituximab is also used