Multiple myeloma


  • Malignant proliferation of plasma cells overproduction of abnormal antibodies (paraproteins or light-chain protein)
    • Osteoclasts are activated through the RANK pathway by the abnormal antibodies leading to osteolytic lesions
  • Symptoms result from accumulation of plasma cells and paraproteins
  • Most common primary bone malignancy
  • More commonly seen in African Americans and males

Clinical Features

  • Percentages below correspond to clinical presentations in newly diagnosed disease
  • Bone (plasma cell proliferation in marrow) lesions in ~80%
    • Pathologic fractures
      • Due to lytic lesions and osteopenia
      • ”Punched-out” lytic lesion on x-ray
      • Frequently involve spine, as well as ribs, skull, extremities
    • Bone pain (even in absence of fracture) in ~60%[1]
      • Commonly in back, ribs, extremities, often worse with movement
  • Renal impairment in 20-40%[2]
    • Ranges from mild creatinine elevation to ESRD
    • Due to light-chain deposition, myeloma cast nephropathy and/or amyloidosis
    • Hypercalcemia exacerbates
    • Vulnerable to further damage from nephrotoxic mediations/contrast
  • Hematologic
    • Anemia in ~70%[3]
    • Due to plasma cell infiltration in marrow +/- renal failure
    • Hyperviscosity syndrome
      • Increase serum viscosity due to paraproteins poor capillary flow and organ congestion
      • Cryoglobulinemic vasculitis
        • Altered mental status, syncope, stroke
    • Rouleaux formation on peripheral smear
  • Neuro
    • Spinal cord compression due to vertebral fracture or collapse or plasmacytoma
    • Intracranial plasmacytoma (rare)
    • Peripheral neuropathy, radiculopathy
  • Hypercalcemia
    • Due to local osteolysis
    • Though overall uncommon as first presentation finding
  • Infection
    • Most common cause of death in patients with multiple myeloma
    • Impaired plasma cell function decreased effective antibody production
    • Often on immunosuppressive chemotherapy or bone marrow transplant meds
    • Splinting due to rib pain/fractures increased pneumonia risk
  • Coagulopathy can occur due to dysfibrinogenemia
Pathological fracture from lytic lesion

Differential Diagnosis


RBC Loss

RBC consumption (Destruction/hemolytic)

Impaired Production (Hypochromic/microcytic)

  • Iron deficiency
  • Anemia of chronic disease
  • Thalassemia
  • Sideroblastic anemia

Aplastic/myelodysplastic (normocytic)

  • Marrow failure
  • Chemicals (e.g. ETOH)
  • Radiation
  • Infection (HIV, parvo)

Megaloblastic (macrocytic)

Bone tumors and their mimics





X-ray of the forearm, with lytic lesions
  • Definitive diagnosis is by biopsy of marrow or plasmacytoma
  • CBC
  • Peripheral smear- may see Rouleaux formation of RBCs, atypical plasma cells
Roleaux formation on peripheral smear
  • BMP, ionized Ca, Mg, phos
    • Paraproteins bind calcium, so non-ionized Ca levels could be falsely elevated
    • Pseudohyponatremia from paraproteinemia
    • Hyperphosphatemia from increased bone turnover
  • Serum and urine testing for monoclonal protein (to aid in initial diagnosis if patient not already known to have MM)
    • SPEP and UPEP electrophoresis
    • Urine analysis will show large, waxy, laminated casts due to monoclonal proteins known as Bence Jones proteinuria
      • Urine dipstick will be negative for protein as it detects albumin rather than monoclonal proteins
  • Most common monoclonal proteins in order are as follows: IgG, IgA, Kappa > lambda light chains
  • Other work up contingent on presentation:
    • MRI spine: low threshold if any clinical evidence of cord compression
    • Plain films of suspected pathologic fractures
    • Infectious work up
    • ECG can show shortened QT interval secondary to hypercalcemia



  • Consideration for heme/onc consultation

See Also

External Links


  1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33.
  2. Eleutherakis-Papaiakovou V, Bamias A, Gika D, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma 2007;48:337-341.
  3. Birgegard G, Gascon P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European Cancer Anaemia Survey. Eur J Haematol 2006;77:378-386.
  • Multiple Myeloma. Antonio Palumbo, M.D., and Kenneth Anderson, M.D. N Engl J Med 2011; 364:1046-1060March 17, 2011. DOI: 10.1056/NEJMra1011442