• A soft tissue cancer with features of skeletal muscle differentiation. Prognostic classification of rhabdomyosarcoma (RMS) currently depends on the following:
    • Anatomic site of disease (stage)
    • Extent of resection and spread (group)
    • Underlying histology (alveolar vs. embryonal or other variants, e.g., botryoid)


  • The most common pediatric soft tissue sarcomas (tumors of mesenchymal origin)
  • Accounts for ∼5% of childhood cancer
  • Boys at slightly increased risk compared to girls (incidence by gender of 1.5:1)
  • Peaks in children <7 years of age, with another smaller peak in late adolescence
  • Median age at diagnosis is 5 years.


  • 4.5 cases per 1 million children per year
  • U.S. annual incidence of about 350 cases per year

Risk Factors

  • Radiation exposure, including a possible connection to in utero exposure
  • High birth weight associated with embryonal rhabdomyosarcoma in one study.


  • About 90% of cases are sporadic.
  • Several predisposing conditions:
    • Li-Fraumeni (autosomal dominant)
      • TP53 mutation leads to cancer predisposition through loss of DNA damage signaling.
      • Increased risk for soft tissue sarcomas, osteosarcoma, adrenocortical carcinoma, choroid plexus carcinoma, leukemias, breast cancer, and other cancers
    • Beckwith-Wiedemann syndrome (sporadic)
      • Improper epigenetic regulation of 11p15 leads to an overgrowth syndrome.
      • Increased risk of a range of embryonal cancers early in life, including Wilms tumor, hepatoblastoma, and RMS
    • Neurofibromatosis type I and Costello syndrome (autosomal dominant)
      • Mutational activation of HRAS (Costello) or loss of the RAS-negative regulator NF1 (neurofibromatosis) leads to unchecked RAS signaling and increased risk for RMS.

General Prevention

  • No standard approach because most cases are sporadic
  • Avoidance of radiation in patients with known predisposing syndromes (e.g., Li-Fraumeni syndrome)


  • Alveolar rhabdomyosarcomas (ARMS; about 20% of cases) carry translocations t(2;13) or t(1;13) resulting in the fusion transcription factors PAX3-FOXO1 or PAX7-FOXO1.
    • Alveolar histology and presence of PAX3-FOXO1 is a poor prognostic factor.
    • Animal models combining expression of PAX3-FOXO1 and loss of either TP53 or CDKN2A recapitulate ARMS.
  • Embryonal rhabdomyosarcomas (ERMS; about 60% of cases) commonly carry mutations in the RAS pathway as well as loss of heterozygosity at 11p15.
    • Animal models of ERMS target activating Ras mutations to myogenic progenitor cells.
    • The botryoid subtype of ERMS includes submucosal tumors with a favorable prognosis.
  • The remainder of cases include pleomorphic or anaplastic histologies and also harbor a poor prognosis.

Commonly Associated Conditions

  • Syndromes listed in “Genetics” have the highest association.
  • CNS and genitourinary (GU) anomalies (Chiari malformations, horseshoe kidneys, etc.) in one autopsy-based report

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