Rhabdomyosarcoma
Basics
DESCRIPTION
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.
EPIDEMIOLOGY
- 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)
INCIDENCE
- 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.
RISK-FACTORS
GENETICS
- 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)
GENERAL-PREVENTION
- No standard approach because usually sporadic
- Avoidance of radiation in patients with known predisposing syndromes (e.g., Li-Fraumeni syndrome)
PATHOPHYSIOLOGY
- 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.
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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Citation
Cabana, Michael D., editor. "Rhabdomyosarcoma." Select 5-Minute Pediatrics Topics, 7th ed., Wolters Kluwer Health, 2015. Medicine Central, im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14106/all/Rhabdomyosarcoma.
Rhabdomyosarcoma. In: Cabana MDM, ed. Select 5-Minute Pediatrics Topics. Wolters Kluwer Health; 2015. https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14106/all/Rhabdomyosarcoma. Accessed December 2, 2024.
Rhabdomyosarcoma. (2015). In Cabana, M. D. (Ed.), Select 5-Minute Pediatrics Topics (7th ed.). Wolters Kluwer Health. https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14106/all/Rhabdomyosarcoma
Rhabdomyosarcoma [Internet]. In: Cabana MDM, editors. Select 5-Minute Pediatrics Topics. Wolters Kluwer Health; 2015. [cited 2024 December 02]. Available from: https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14106/all/Rhabdomyosarcoma.
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