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Updated: Sep 22 2017

Multiple Myeloma

Snapshot
  • A 65-year-old man presents with generalized "pain in his bones," and a recent fracture that occurred while he was walking.  He has also had multiple infections recently.  Recent lab work demonstrated hypercalcemia, an increased β2 microglobulin, an increase BUN and Cr as well as a peripheral smear that demonstrated an abnormal stacking of RBC's.
Introduction
  • Multiple myeloma is cancer of monoclonal plasma cells
    • produces large amounts of IgG (55% of cases) or IgA (25% of cases)
  • Epidemiology
    • most common primary tumor of the bone/ bone marrow in patients > 50 years of age
Presentation
  • Symptoms
    • bone pain
      • back pain can be the presenting symptom 
    • sequelae associated with hypercalcemia
    • sequelae associated with renal failure
Evaluation
  • Serum protein electrophoresis
    • monoclonal immunoglobulin spike (M protein)
  • Urinalysis
    • Ig light chains (Bence Jones protein)
  • Peripheral blood smear
    • RBC rouleaux formation
      • Igs coat RBC and neutralize the ionic charge than normally repells RBCs
  • Bone marrow aspiration
    • proliferation of large monoclonal plasma cells      
      • "fried-egg" appearance
  • Serology
    • hypercalcemia
      • result of bone degradation due to cytokine production that activates RANKL receptor on osteoclasts
    • prolonged bleeding time
  • Imaging 
    • punched-out lytic bone lesions on radiograph
Differential
  •  Waldenstrom's macroglobulinemia  
    • presentation
      • generalized lymphadenopathy
      • bleeding
        • IgM disrupts platelet aggregation
      • sequelae of blood hyperviscosity
        • retinal hemorrhage
        • stroke
    • evalutation
      • serum protein electrophoresis 
        • M spike = IgM 
        • unlike multiple myeloma which is IgA/G
      • imaging 
        • no lytic bone lesions
  • Monoclonal gammopathy of undetermined significance (MGUS)
    • increased gamma globulin on serum electrophoresis but no symptoms of multiple myeloma are present 
    • can progress to MM (1% per year)
Management
  • Multiple myeloma is a disease of plasma cells (thus the treatments below)
    • mephalan
      • chemotherapy drug - nitrogen mustard alkylating
    • steroids
      • reduce many side effects associated with chemotherapy
    • thalidomide, lenalidomide
      • immunomodulatory agent
    • bortezomib
      • proteasome inhibitor
    • bone marrow transplant
      • definitive therapy, preferable in young patients
Prognosis, Prevention, and Complications
  • May lead to
    • renal insufficiency
    • ↑ susceptibility to infection
    • anemia
    • primary amyloidosis (AL)
  • Poor prognosis
    • high urine levels of β2 microglobulin suggest severe myelomatous cell burden
    • β2 microglobulin can be used to track severity and response to treatment
Question
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