Rhabdomyosarcoma is the third most common solid cancer outside the central nervous system in children (after Wilms tumor Wilms Tumor Wilms tumor is an embryonal cancer of the kidney composed of blastemal, stromal, and epithelial elements. Genetic abnormalities have been implicated in the pathogenesis, but familial inheritance... read more and neuroblastoma Neuroblastoma Neuroblastoma is a cancer arising in the adrenal gland or less often from the extra-adrenal sympathetic chain, including in the retroperitoneum, chest, and neck. Diagnosis is confirmed by biopsy... read more ). About 400 to 500 cases occur in the US each year, and rhabdomyosarcoma accounts for 3% of all childhood cancers (1 References Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more ). Rhabdomyosarcoma belongs to a group of tumors known as soft-tissue sarcomas and is the most common cancer in this group.
Two thirds of rhabdomyosarcomas are diagnosed in children < 7 years of age. The disease is more common among White children than Black children (largely because frequency is lower in Black girls) and is slightly more common among boys than girls.
Even though rhabdomyosarcomas can occur in both children and adults, they differ significantly in terms of histologic type, site of disease, and overall outcome (2 References Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more ).
Histology
There are 2 major histologic subtypes of rhabdomyosarcoma:
Embryonal: Characterized by loss of heterozygosity on chromosome 11p15.5
Alveolar: Associated with translocation t(2;13), which fuses the PAX3 gene with the FOXO1 (FKHR) gene, and t(1;13), which fuses the PAX7 gene with the FOXO1 (FKHR) gene
Location
Although rhabdomyosarcoma can occur almost anywhere in the body, the cancer has a predilection for several sites (3 References Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more ):
Head and neck region (about 35%), usually in the orbit or nasopharyngeal passages: Most common among school-aged children
Genitourinary system (about 25%), usually in the bladder, prostate, or vagina: Usually occurring in infants and toddlers
Extremities (about 20%): Most common among adolescents
Trunk/miscellaneous sites (about 20%)
Approximately 15 to 25% of children present with metastatic disease. The lung is the most common site of metastasis; bone, bone marrow, and lymph nodes are other possible sites.
References
1. Siegel RL, Miller KD, Fuchs HE, et al: Cancer Statistics, 2022. CA Cancer J Clin 72(1):7–33, 2022. doi: 10.3322/caac.21708
2. Sultan I, Qaddoumi I, Yaser S, et al: Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: An analysis of 2,600 patients. J Clin Oncol 27(20):3391–3397, 2009. doi: 10.1200/JCO.2008.19.7483
3. Linardic CM, Wexler LH: Rhabdomyosarcoma: Epidemiology and Genetic Susceptibilty. In Pizzo and Poplack's Pediatric Oncology, 8th ed., edited by SM Blaney, LJ Helman, PC Adamson. Philadelphia, Wolters Kluwer, 2021, p. 693.
Symptoms and Signs of Rhabdomyosarcoma
Children do not typically have systemic symptoms such as fever, night sweats, or weight loss. Usually, children present with a firm, palpable mass or with organ dysfunction due to impingement on the organ by the cancer.
Orbital and nasopharyngeal cancers may cause tearing, eye pain, or proptosis. Nasopharyngeal cavity cancers may cause nasal congestion, a change in voice, or mucopurulent discharge.
Genitourinary cancers cause abdominal pain, a palpable abdominal mass, difficulty urinating, and hematuria. Vaginal tumors can manifest with mucosanguineous discharge with a polypoid mass protruding from the vagina.
Extremity cancers appear as firm, indiscrete masses anywhere on the arms or legs. Regional lymph node spread occurs frequently, and metastases in the lungs, bone marrow, and lymph nodes can occur and usually do not cause symptoms.
Diagnosis of Rhabdomyosarcoma
CT or MRI
Biopsy or excision
Masses are evaluated by CT, although head and neck lesions are often better defined by MRI. Diagnosis of rhabdomyosarcoma is confirmed by biopsy or excision of the mass.
The standard metastatic evaluation includes chest CT, positron emission tomography (PET)–CT, bone scan, and bilateral bone marrow aspiration and biopsy.
Treatment of Rhabdomyosarcoma
Surgery and chemotherapy
Radiation therapy for residual bulk or microscopic disease
The treatment approach for rhabdomyosarcoma is multimodal, consisting of chemotherapy in combination with surgery, radiation therapy, or both.
Complete excision of the primary cancer is recommended when it can be done safely. Because the cancer is responsive to chemotherapy and radiation therapy, aggressive resection is discouraged if it may result in organ damage or dysfunction.
Children in all risk categories are treated with chemotherapy; the most commonly used drugs are vincristine, actinomycin D (dactinomycin), cyclophosphamide, doxorubicin, ifosfamide, and etoposide. Topotecan and irinotecan are other drugs that have activity against this cancer.
Radiation therapy is generally recommended for children with residual bulk disease or microscopic residual tumor after surgery and for children with intermediate-risk or high-risk disease.
Prognosis for Rhabdomyosarcoma
Prognosis is based on
Cancer location (eg, prognosis is better with nonparameningeal head/neck and nonbladder/nonprostate genitourinary cancers)
Completeness of resection
Presence of metastasis
Age (prognosis is worse for children < 1 year of age or > 10 years of age
Histology (embryonal histology is associated with a better outcome than alveolar histology)
Combinations of these prognostic factors place children in a low-risk, intermediate-risk, or high-risk category. A complex risk stratification system exists (see the National Cancer Institute's stage information for childhood rhabdomyosarcoma). Treatment intensifies with each risk category, and overall survival ranges from > 90% in children with low-risk disease to < 50% in children with high-risk disease (1 Prognosis references Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more , 2 Prognosis references Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more , 3 Prognosis references Rhabdomyosarcoma is a cancer arising from embryonal mesenchymal cells that have potential to differentiate into skeletal muscle cells. It can arise from almost any type of muscle tissue in any... read more ).
Prognosis references
1. Walterhouse DO, Pappo AS, Meza JL, et al: Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 32(31):3547–3552, 2014. doi: 10.1200/JCO.2014.55.6787. Clarification and additional information. J Clin Oncol 36(14):1459, 2018.
2. Raney RB, Walterhouse DO, Meza JL, et al: Results of the Intergroup Rhabdomyosarcoma Study Group D9602 protocol, using vincristine and dactinomycin with or without cyclophosphamide and radiation therapy, for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 29(10):1312–1318, 2011. doi: 10.1200/JCO.2010.30.4469
3. Oberlin O, Rey A, Lyden E, et al: Prognostic factors in metastatic rhabdomyosarcomas: Results of a pooled analysis from United States and European cooperative groups. J Clin Oncol 26(14):2384–2389, 2008. doi: 10.1200/JCO.2007.14.7207
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
National Cancer Institute: Stage information for childhood rhabdomyosarcoma
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
vincristine |
Oncovin, Vincasar PFS |
dactinomycin |
Cosmegen |
cyclophosphamide |
Cyclophosphamide, Cytoxan, Neosar |
doxorubicin |
Adriamycin, Adriamycin PFS, Adriamycin RDF, Rubex |
ifosfamide |
Ifex |
irinotecan |
Camptosar |
