Medicine & USMLE

Multiple Myeloma

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Plasma Cell Dyscrasias
  1. Waldenstrom Macroglobulinemia
  2. 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