Multiple Myeloma

• Pathogenesis of monoclonal gammopathy: proliferation of single clone of plasma cells with production of immnologically homogenous protein (M protein)
  • Protein can be intact immunoglobulin (heavy and light chain), light chain only, or heavy chain only
  • Pathologic consequences of such protein:
    • Cold agglutinins
    • Cryoglobulinemia
    • Increased serum viscosity
    • Amyloidosis
    • Neuropathy
• Detection of monoclonal proteins
  • Diagnostic modalities
    • Serum protein immunoelectrophoresis (electrophoresis + immunofixation)
      • Can yield false negatives in light chain disease, as Bence Jones proteins are rapidly cleared by kidney
    • Serum free light chains: looks at ratio between kappa and lambda light chains
      • More sensitive that 24h urine in detecting light chain disease
      • Can miss heavy chain or intact immunoglobulin disease
      • Does not quantify amount of M protein burden
    • Spot protein:creatinine: rough quantitation of protein, but does not classify subtype
    • Urine dipstick: does not detect Bence Jones protein
    • Urine protein immunoelectrophoresis: can be cumbersome to obtain
  • Recommended approach is to send SPIE and serum free light chains on initial evaluation
• Differential diagnosis of monoclonal gammopathy
  • Plasma cell dyscrasias: MGUS, AL amyloid, solitary plasmacytoma, multiple myeloma
  • Lymphoma
  • Hepatitis C
  • Rheumatologic disorders (RA, SLE)
• Spectrum of disorders:
  • MGUS: M protein < 3g/dL, <10% clonal plasma cells in BM, no end-organ damage
  • Smoldering myeloma: M protein >3g/dL or >10% clonal plasma cells in BM, no end-organ damage
  • Symptomatic myeloma: M protein, >10% clonal plasma cells (or plasmacytoma), end-organ damage (CRAB: hyperCalcemia, Renal disease, Anemia, Bony lesions)

(Christopher Woo MD, 1/6/11)