Rhabdomyosarcoma (RMS) is a malignant tumor of soft tissue assumed to originate from the same pluripotent mesenchyme cell as striated skeletal muscle. It occurs mainly as primary malignancy but can also be a component of heterogeneous neoplasias, like malignant teratoma.

  • Common primary sites:
    • Head and neck 25% presentation (common in young children, almost always embryonal type)
    • Genitourinary 31% of cases (mostly embryonal type)
    • Musculoskeletal 13% of cases (most common in extremities primary sites in adolescents and adults, alveolar subtype)
  • The 4th edition of the WHO Classification of Tumours of Soft Tissue and Bone of RMS describes four major subtypes:
    • Embryonal RMS (ERMS): represents 60–70% among all RMS. Has early onset and is the most common subtype in children. Commonly presents in the head, neck, and genitourinary areas. ERMS is subdivided into:
      • Classic
      • Botryoid (6% overall embryonal): seen in infants, although can happen <4-year-old patients
      • Spindle cell: 3% of cases and affects young children
        • Both botryoid and spindle cell variants have better prognosis than the classical one.
    • Alveolar RMS (ARMS): represents 30% of pediatric cases, very aggressive subtype; more common in the trunk, perineum/perianal area, and extremities
    • Spindle cell/sclerosing: most frequently seen at the paratesticular site
    • Anaplastic (children)/pleomorphic (adults) seen in patients aged 30 to 50 years, rarely in children, represents 1% of all RMS, mostly associated with Li-Fraumeni symptoms
  • Clinicopathologic and molecular studies have now delineated five to six distinct subfamilies of RMSs (1).


It presents most commonly in children and young adults rather than adults. Male sex was directly associated with RMS. When diagnosed in adults, it is often found in more unfavorable sites and is associated with a more aggressive course.


  • 4.5 cases of RMS per 1 million children per year, in children, adolescents, and young adults.
  • RMS accounts for 60% of sarcomas in children and adolescents. 50% of pediatric cases occur before the age of 10 years.
  • In adults, RMS represents 3% of all soft tissue sarcomas in adults.
  • More common in the black population


  • RMS comprises 3.5% of childhood cancers overall.
  • The more frequent in males (male:female ratio, 1:5)

Etiology and Pathophysiology

Genetic characteristics vary according to the RMS subtype:

  • Alveolar:
    • Associated with recurrent Forkhead box O1 (FOXO1) fusions, (found in 90% of cases)
    • t(2;13)(q35;q14); causing PAX3-FOXO1 fusion
    • t(1;13)(p36;q14); causing PAX7-FOXO1 fusion
    • t(X:2)(q13;q35); causing PAX3-FOXO4 fusion
    • t(2;2)(q35;p23); causing PAX3-NCOA1 fusion
    • t(2;8)(q35;q13); causing PAX3-NCOA2 fusion
    • t(8;13)(p12;q13); causing FOXO1-FGFR1 fusion
  • Embryonal:
    • Multiple complex genetic aberrations, including MYOD1 mutations
    • Loss or uniparental disomy of 11p15.5 +2, +8, +11, +12, +13, +20 affecting the genes IGF-2, H19, CDKN1C, and/or HOTS
  • Spindle cell/sclerosing RMS:
    • 8q13 rearrangements involving SRF-NCOA2 and TEAD1-NCOA2

Risk Factors

Although not yet proven, RMS has been associated with high birth weight, large gestational size for age, exposure to recreational drugs and/or radiation while in utero, low socioeconomic status, and the genetic conditions as described below.

Commonly Associated Conditions

  • Beckwith-Wiedemann syndrome (11p15 mutations) presents as fetal overgrowth.
  • Costello syndrome (germline HRAS mutations) presents as postnatal growth delay and morphologic abnormalities (including macrocephaly).
  • Li-Fraumeni (germline TP53; known as p53 mutations)
  • Neurofibromatosis type I (NF1 mutations)
  • Noonan syndrome (PTPN11 mutations)
  • Pleuropulmonary blastoma (DICER1 mutations)

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