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Tumor biology and incidence

  • Most common primary malignant tumor of bone (approximately 50% of malignant bone tumors)
  • Malignant tumor of plasma cells, characterized by widespread osteolytic bone destruction
  • Often associated with refractory anemia, hypercalcemia, renal dysfunction, and decreased resistance to infection
  • Less common features: amyloid deposition, derangement of coagulation, cryoglobulinemia, and elevated serum viscosity


  1. Solitary plasmacytoma (single lesion)
  2. Multiple sites in bone (myeloma)
  3. Multiple sites in bone and organs (myelomatosis)


  • Age range: 20 to 80 years
  • Average age: 60 years


M:F = 1:1


  • Pain is cardinal early symptom
  • Pain classically worse during day and with activity
  • Patients often treated for other causes of skeletal pain before diagnosis
  • Pathologic fracture occurs in 20% of patients
  • Fatigue and weakness usually present

Physical findings

Weight loss often evident

Blood work

  • Elevation of BUN and creatinine common; poor prognosis
  • Anemia and elevated ESR common
  • Hypercalcemia frequently present at some stage of disease
  • Serum phosphate and alkaline phosphatase generally normal
  • Perform serum immune electrophoresis to make diagnosis (monoclonal elevation of IgG, IgA and Bence Jones light chains most common finding)
  • Perform peripheral blood smear to detect rouleaux formation
  • Check coagulation if surgery is planned

Plain films

  • Vertebral bodies, ribs, skull, pelvis, and sternum more commonly affected than femur, tibia, radius, and humerus
  • Small bone involvement rare

Variable: Surrounding disease and changes of osteoporosis may be extensive

Tumor effect on bone
  • Pure osteolytic destruction of the bone common
  • Rarely, focal, or diffuse sclerotic lesions may be seen
Bone response to tumor

No surrounding sclerosis or periosteal reaction



  • Slight cortical thinning; can have endosteal scalloping
  • Severe osteoporosis often present
Soft tissue mass


Bone scan

Often cold in myeloma, but can be hot

Differential diagnosis

  • Osteoporosis
    • May be indistinguishable from osteoporosis in spine; multiple compression fractures
  • Metastasis
  • Brown tumor
  • Giant cell tumor
  • Fibrosarcoma
  • Malignant fibrous histiocytoma
  • Lymphoma
  • Osteomyelitis
  • Chordoma (in the sacrum)
  • Low-grade chondrosarcoma (especially in pelvis)


  • Gross: Grey-tan or "fish-flesh" type tissue
  • Microscopic: Infiltration by atypical plasma cells
  • Immunostaining shows monoclonal staining for kappa or lambda light chains

Diagnosis and treatment

  • Serum immune electrophoresis generally diagnostic
    • If electrophoresis negative, consider biopsy of remote bone marrow
  • Staging system for myeloma used to predict survival by attempting to estimate total body tumor burden
    • Staging based on the values for serum hemoglobin, serum calcium, serum M component, and the extent of skeletal involvement as determined in the radiographic work-up
    • Tumor burden categorized as low (Stage I), intermediate (Stage II), or high (Stage III).
  • Patients further divided based on renal function (serum creatinine < 2mg/dl = A, and serum creatinine > 2mg/dl = B).
  • Stage and renal function are combined to predict survival.
  • Chemotherapy mainstay of treatment
    • Recent randomized trials suggest intensive chemotherapy with autogenous bone marrow transplant will increase length of event-free survival
    • With standard chemotherapy, 15% of patients die within the first 6 months of diagnosis; thereafter, mortality rate approximately 15% per year
    • Results are likely improved with intensive chemotherapy supported by autogenous marrow transplantation
  • Pamidronate demonstrated effective in management of hypercalcemia and (in long-term use) in controlling bone symptoms
  • Radiation can effectively control localized lesions causing pain or limiting activity
  • If radiation not successful, surgery may be required for impending pathologic fracture or spinal compression

Solitary myeloma (plasmacytoma)

  • Rare lesion
  • Criteria for diagnosis
    • Solitary lesion on skeletal survey
    • Histologic confirmation of plasmacytoma after biopsy of lesion
    • Bone marrow plasmacytosis of 10% or less
    • Negative screening MRI of spine
    • Negative serum immunoelectrophoresis
  • May be the sole manifestation of already disseminated process
  • Disease may remain localized or progress with time
  • Solitary myeloma may be resected or (more commonly) treated locally with irradiation

Sclerosing myeloma

  • More common in younger males
  • Lesions osteolytic, with reactive sclerosis (as opposed to usual, non-sclerosing myeloma)
  • Use the mnemonic POEMS
    • Polyneuropathy (in 30-50 %)
    • Organomegaly (liver and spleen)
    • Endocrine (gynecomastia, amenorrhea)
    • Monoclonal Gammopathy
    • Skin hyperpigmentation and hirsutism

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