A soft tissue cancer with features of skeletal muscle differentiation. Prognostic classification of rhabdomyosarcoma (RMS) currently depends on:
- Anatomic site of disease (stage)
- Extent of resection and spread (group)
- Presence of a FOXO1 gene fusion (either PAX3-FOXO1 or PAX7-FOXO1). This has supplanted histologic subtype (alveolar vs. embryonal) in North America.
- 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)
- 4.5 cases per 1 million children per year
- U.S. annual incidence is approximately 350 cases per year.
- Age distribution
- Peaks in children <7 years, with another smaller peak in late adolescence
- Median age at diagnosis is 5 years.
- About 90% of cases are sporadic.
- Several predisposing conditions:
- Li-Fraumeni (autosomal dominant)
- TP53 mutation leads to cancer predisposition due to inadequate response to DNA damage.
- 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.
- Li-Fraumeni (autosomal dominant)
- No standard approach because usually sporadic
- Avoidance of radiation in patients with known predisposing syndromes (e.g., Li-Fraumeni syndrome)
- Chromsomal translocations (most commonly t[2;13] or t[1;13]) create fusion transcription factors PAX3-FOXO1 and PAX7-FOXO1.
- Fusions are usually found in alveolar histology tumors, but fusion-negative alveolar cases have a superior prognosis.
- Animal models combining expression of PAX3-FOXO1 and loss of either TP53 or CDKN2A recapitulate RMS.
- Fusion-negative RMS (~60% of cases) commonly carry mutations in the RAS pathway, as well as loss of heterozygosity at 11p15.
- Animal models of fusion-negative RMS target activating RAS mutations to myogenic progenitor cells.
- Distinct histologies include pleomorphic or anaplastic RMS, which harbor poor prognoses.
Commonly Associated Conditions
- Syndromes listed in “Genetics” section have the highest association.
- Radiation exposure, including a possible connection to in utero exposure.
- Single studies showed an association with high birth weight or incomplete childhood vaccination, respectively.
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Cabana, Michael D., editor. "Rhabdomyosarcoma." 5-Minute Pediatric Consult, 8th ed., Wolters Kluwer, 2019. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617335/all/Rhabdomyosarcoma.
Rhabdomyosarcoma. In: Cabana MDM, ed. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617335/all/Rhabdomyosarcoma. Accessed June 4, 2023.
Rhabdomyosarcoma. (2019). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult (8th ed.). Wolters Kluwer. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617335/all/Rhabdomyosarcoma
Rhabdomyosarcoma [Internet]. In: Cabana MDM, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. [cited 2023 June 04]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617335/all/Rhabdomyosarcoma.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Rhabdomyosarcoma ID - 617335 ED - Cabana,Michael D, BT - 5-Minute Pediatric Consult UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617335/all/Rhabdomyosarcoma PB - Wolters Kluwer ET - 8 DB - Pediatrics Central DP - Unbound Medicine ER -