• Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor presumed to originate from a mesenchymal cell line shared with striated skeletal muscle.
  • Occurs mainly as primary malignancy but can also be a component of heterogeneous neoplasms
    • WHO classification of soft tissue tumors describes four main RMS subtypes:
      • Embryonal RMS (ERMS): 60% of RMS cases
        • Early onset and the most common subtype in children
        • Commonly presents in the head, neck, and genitourinary areas
        • Subdivided into:
          • Classic
          • Botryoid (6% overall embryonal): seen in infants, although can happen in <4-year-old patients
          • Spindle cell: 3% of cases and affects young children
          • Both botryoid and spindle cell variants have better prognosis than the classic variant
      • Alveolar RMS (ARMS): 20% of pediatric cases
        • Aggressive subtype
        • More common in the trunk, perineum/perianal area, and extremities
      • Spindle/Sclerosing: approximately 10% of cases
        • Mostly found in the paratesticular region
      • Anaplastic (children)/pleomorphic (adults): <10% of cases
        • Typically seen in patients aged 30 to 50 years (rarely in pediatric population)
        • Associated with Li-Fraumeni symptoms
        • Demonstrates hyperchromatic enlarged nuclei
    • Pathologic and molecular studies have now delineated up to five or six distinct subfamilies of RMS.
    • Common primary sites:
      • Head and neck (25%) presentation (common in young children, usually embryonal type)
      • Genitourinary (31%, mostly embryonal type)
      • Musculoskeletal (13%, most common in extremities primary sites in adolescents and adults, alveolar subtype)


  • RMS is the most common soft tissue sarcoma in pediatric population.
  • Common metastatic sites: bone marrow, lung, lymph nodes


  • 4.5 cases of RMS per 1 million children per year
  • Accounts for 50% of all soft tissue sarcomas in children and adolescents
    • 50% of pediatric cases occur before the age of 10 years (often before age 6 years).


  • Represents 3% of all pediatric tumors and 1% of all adult tumors
  • Slight predilection for males (1.3:1 male-to-female ratio)
  • More common in the African-American population

Etiology and Pathophysiology

  • Originates from rhabdomyoblast cell
  • Tumor is often >5 cm in size with poorly circumscribed border, white coloration, and infiltrative features.

Genetic characteristics vary according to the RMS subtype:

  • Alveolar:
    • Linked to recurrent Forkhead box O1 (FOXO1) fusions (identified in 90% of cases)
    • t(1;13)(p36;q14), causing formation of the fusion oncogenes PAX7-FOXO1
    • t(2;13)(q35;q14), causing formation of the fusion oncogenes PAX3-FOXO1
  • Embryonal:
    • Multiple complex genetic aberrations, including MYOD1 mutations
    • Loss or uniparental disomy of 11p15.5 +2, +8, +11, +12, +13, +20 affecting genes IGF-2, H19, CDKN1C, and/or HOTS
  • Spindle cell/sclerosing:
    • 8q13 rearrangements involving SRF-NCOA2 and TEAD1-NCOA2

Risk Factors

Largely unknown; however, appears to be increased risk of RMS in setting of:

  • Rapid growth in utero
  • Radiation exposure in utero
  • Lower socioeconomic status
  • Recreational drug use during pregnancy

Commonly Associated Conditions

  • Beckwith-Wiedemann syndrome (11p15 mutations)
  • Costello syndrome (germline HRAS mutations)
  • Li-Fraumeni syndrome (germline TP53; known as p53 mutations)
  • Neurofibromatosis type I (NF1 mutations)
  • Noonan syndrome (PTPN11 mutations)

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