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Feedback Haematology

Multiple Myeloma

  • MM is characterised by a triad of abnormalities
    • Accumulation of plasma cells in the BM
    • Bone lesions – discrete or diffuse (see below)
    • Production of a Monoclonal Ig

Epidemiology

  • 2nd MC lymphoid malignancy in Caucasians after CLL
  • MC in older people and men
  • Increased incidence in people in petroleum, leather and asbestos industries

Clinical features

Bone lesions – caused by accumulation of plasma cells in the BM, with dissolution of the bone

  • Bone pain and pathologic fractures – MC presenting complaints
  • Sharp ‘punched out’ Osteolytic lesions – MC in vertebra, ribs, skull, pelvis, femur
  • Less common – diffuse osteoporosis without discrete osteolytic lesions
  • Bone is eroded due to increased osteoclast activity
    • Osteoclasts are stimulated by factors produced by plasma cells – OAFs (osteoclast activating factors)

Infections – MCC of death in MM pts

  • Normal Ig production is suppressed – pts susceptible to S.pneumoniae, S.aureus, E.coli
  • Pneumonitis and Pyelonephritis are common infections

Renal disease – 2nd MCC of death

  • Myeloma cast nephropathy
    • Large tubular casts in urine sediment (light chain + Tamm-Horsfall (THP))
    • The abnormal proteins (Ig) bind with THP >> form large tubular casts which are too big to pass >> blockage >> kidney disease
  • Malignant prolif of plasma cells in BM with prod of Ig
    • Ig light chains (AKA abnormal paraproteins) >> BJ proteins >> toxic to tubular system
    • Light chains are filtered at glomeruli and appear as BJ proteins
  • Hypercalcemia – causes inability to concentrate urine (polyuria)
    • Predisposes to dehydration and prerenal azotemia
  • Nephrotic syndrome – due to proteinuria
  • Renal amyloidosis – due to Ig fragments precipitating as a β-pleated sheet

Hypercalcemia

  • Due to excess bone resorption
  • Can lead to weakness, confusion, lethargy, loss of renal concentrating ability

Diagnosis

  • Dx depends on presence of 3 features
    • A monoclonal Ig protein in serum/urine – electrophoresis (IgG kappa is MC)
    • Bone lesions – CTI/MRI
    • Plasmacytosis in BM – >10% plasma cells on BM aspirate
  • Anemia is often the presenting feature in MM
  • Hypergammaglobulinemia
  • Hypercalcemia, azotemia
  • ALP levels normal as no activation of osteoblasts
  • M spike
  • FISH – chromosome abnormalities
  • Blood smear
    • Shows stacked lines of erythrocytes – rouleaux (see pic)

Staging – see table.  Tumour burden

Complications

  • Spinal cord compression
  • Amyloidosis – AL (light chain)
  • Hyperviscosity syndrome

Treatment

  • Standard chemo – melphalan + prednisone
  • Combo chemo – VDD
    • Vincristine, doxorubicin, dexamethasone
  • Eventually disease becomes resistant to chemo
  • Saline infusion and diuresis for hypercalcemia
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