Sarcoma Etiology and Genetic Conditions


  • No evident, clearly defined etiologic factor

Genetic Conditions

  • Neurofibromastosis type 1 (von Recklinghausen's Disease)
    • an autosomal dominant disorder
    • affecting 1 in 3000 individuals
    • causes intracranial optic pathway glioma
    • causes extracranial malignant Schwann cell tumors.
  • Retinoblastoma
    • osteosarcoma
    • Genetic mutations (Suppressor genes Rb-1 and p53); MDM2gene
  • Familial polyposis (Gardner’s Syndrome )
    • desmoid tumor
  • Li Fraumeni Syndrome (p53 defect) is characterized by familial cluster of
    • Sarcoma 12% (of sarcoma, osteosarcoma is common)
    • breast cancer 25%
    • leukemia
    • adrenal carcinoma
    • brain tumors
    • lung cancer
    • skin cancer
    • and pancreatic cancer.

Enviromental Factors

  • Chronic lymphedema (Stewart-Treves Syndrome) - angiosarcoma
  • Trauma (not a etiological factor)
  • Chronic irritation/foreign body reaction
  • Chemical exposure
  • Radiation (see below)

Radiation Induced Sarcoma (RIS)


  • Malignant Fibrous Histiocytoma may be the most frequent secondary sarcoma
  • Angiosarcoma is most common after breast radiation
  • Overall incidence of RIS at 10 year is 0.03%


  • osteosarcoma risk is linear to radiation dose.
  • Both radiation and chemotherapy have excess risk of secondary sarcoma
  • Risk of RIS is 111 fold with neutron radiation.
  • The RR with photons is ~ 3
  • Median latency is 10.5 yrs.

Tumor Markers

Histology Cells of Origin markers
Leiomyosarcoma Smooth muscle smooth muscle-specific-actin
Angiosarcoma Vascular endothelial factor VIII, CD34
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