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Updated: Dec 27 2021

Multiple Myeloma


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  • Snapshot
    • A 65-year-old man presents to his primary care physician with generalized fatigue and lower back bone pain. He reports an unexpected 20-pound weight loss over the course of 3 months. Physical examination is notable for conjunctival pallor and tenderness upon palpation of the lower spine. Laboratory studies are notable for a normocytic, normochromic anemia, hypercalcemia, and renal insufficiency. Urine electrophoresis is notable for Bence Jones proteins.
  • Introduction
    • Overview
      • neoplastic proliferation of plasma cells within the bone marrow
        • leads to the production of monoclonal immunoglobulin (Ig)
          • mostly IgG (52%) and IgA (21%)
        • results in skeletal destruction
  • Epidemiology
    • Demographics
      • older adults
        • median age is 66 years of age
    • Risk factors
      • monoclonal gammopathy of undetermined significance (MGUS)
    • Pathophysiology
      • clonal malignant plasma cell proliferation
    • Associated conditions
      • Fanconi syndrome
      • renal tubular acidosis type 2
      • ↑ susceptibility to infection
      • primary amyloidosis
  • Presentation
    • Symptoms
      • fatigue
        • secondary to anemia
      • bone pain
        • especially in the back and chest
      • radiculopathy
        • especially in the thoracic or lumbosacral area
        • it's the most common neurological complication of multiple myeloma
        • secondary to
          • paravertebral plasmacytoma
          • bone collapse
      • peripheral neuropathy
        • rare and usually secondary to amyloidosis
      • sequelae associated with hypercalcemia
        • e.g., constipation, abdominal pain, muscle pain, and frequent urination
      • edema
        • secondary to effects of amyloidosis on kidneys
  • Imaging
    • Radiography
      • indication
        • can be used as an initial imaging study when evaluating bone pain
          • it is the least sensitive method for detecting skeletal lesions
      • findings
        • lytic bone lesions
    • Whole body low-dose CT scan
      • indication
        • used in most cases to have a baseline assessment of how much the bone is involved
    • MRI whole body (or spine and pelvis)
      • indication
        • when CT scan does not demonstrate bone lesions but there is a high suspicion of multiple myeloma
          • most sensitive in evaluating bone involvement
        • when there is concern for cord compression
    • PET scan
      • indication
        • suspected extramedullary disease
          • most sensitive in evaluating extramedullary involvement
  • Studies
    • Serum labs
      • normocytic, normochromic anemia
        • secondary to
          • bone marrow replacement
          • renal damage
          • hemodilution with large M protein
      • elevated serum creatinine
        • secondary to
          • light chain cast nephropathy (myeloma kidney)
            • Bence Jones protein on urine electrophoresis
          • hypercalcemia
      • hypercalcemia
        • from osteolytic bone lesions
      • protein electrophoresis of the serum (SPEP)
        • monoclonal immunoglobulin spike (M protein)
      • peripheral blood smear
        • rouleaux formation of red blood cells
          • "stack of coins" appearance
    • Invasive studies
      • bone marrow aspiration
        • ≥ 10% clonal plasma cells
        • multiple plasma cells with a "clock-face" chromatin pattern
      • renal biopsy
        • amyloid desposits will show apple-green birefringence under polarized light with Congo red stain
    • Imaging
      • punched-out lytic bone lesions on radiograph
  • Differential
    • MGUS
      • differentiating factors
        • < 10% clonal plasma cells
        • absence of lytic lesions
        • serum M protein is low
    • Waldenstrom macroglobulinemia
      • differentiating factors
        • IgM gammopathy
        • absence of hypercalcemia, renal involvement, anemia, and bone lytic lesions
  • Treatment
    • Medical
      • chemotherapy
        • indication
          • treatment of choice
            • optimal treatment has not been established yet
  • Complications
    • May lead to
      • ↑ susceptibility to infection
      • anemia
      • primary amyloidosis (AL)
        • cast nephropathy
          • due to excess light chain production
        • peripheral neuropathy
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