Multiple Myeloma
Table of Contents

Pathogenesis

  • A germinal center-derived tumor
  • Mostly B-cell phenotype
  • Ig gene hypermutation in a pattern suggesting antigen selection
    • Reflected in IgM myeloma
  • Anemia in Multiple Myeloma:
    • Tumor cell involvement of the marrow
    • Inadequate erythropoietin responsiveness
      • Suppressive effects of various cytokines on erythropoiesis
      • Effect of renal dysfunction on erythropoietin production
    • High immunoglobulin levels exacerbate the anemia by dilutional effects
    • Symptoms of Anemia:
      • Fatigue, weakness, and occasionally shortness of breath
    • Erythropoietin administration
  • Renal Failure
    • Etiology is multifactorial
    • Development of light chain tubular casts ==> interstitial nephritis (myeloma kidney)
    • Hypercalcemia ==>
      • Osmotic diuresis
      • Volume depletion
      • Prerenal azotemia
      • Calcium deposition and kidney stones
    • Light chain deposition disease
      • More commonly associated with kappa light chain proteins
      • Impaired glomerular filtration
    • Amyloidosis
      • Associated with lambda light chain (especially lambda light chain subtype VI)
      • Nephrotic range proteinuria
    • Renal calcium deposition ==> interstitial nephritis
    • Bence Jones proteins bind to a glycoprotein ==> heterotypic aggregation & deposition in the kidney
    • Use of NSAID
    • Hyperuricemia
    • Nephrotoxic chemotherapeutic agents
    • IV contrast for radiographic studies
    • Bisphosphonate therapy
  • Hypercalcemia and Bone Disease
    • Increase in osteoclast-activating factors produced by the BM microenvironment but also by myeloma cells
      • Increased osteoclast activity
      • Suppressed osteoblast activity
    • Lytic lesions