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The World Health Organization divides soft tissue tumors into 4 categories based on clinical behavior: benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant. Benign soft tissue tumors such as lipoma, nodular fasciitis, and hemangioma predominate in pediatric patients. Certain intermediate-behavior soft tissue tumors, including desmoid-type fibromatosis and dermatofibrosarcoma protuberans, occur frequently in childhood. The more than 30 histologic subtypes of malignant soft tissue tumors comprise approximately 7% of all cancers among children and adolescents. In children, rhabdomyosarcoma (RMS) is by far the most common soft tissue sarcoma, accounting for about 40% of cases. Because RMS predominates, the remaining malignant soft tissue tumors are often referred to as non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).
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PATHOGENESIS AND EPIDEMIOLOGY
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The incidence of soft tissue sarcoma (STS) rises with age across the entire lifespan. However, the distribution of tumor types differs by age. Certain entities such as infantile fibrosarcoma occur exclusively in infants and young children, whereas other tumor types such as intimal sarcoma virtually never occur in pediatric patients. In childhood, the most common entities are RMS, synovial sarcoma, malignant peripheral nerve sheath tumor, and undifferentiated sarcoma. Rhabdomyosarcoma predominates in children under 10 years of age, whereas NRSTS is more common in older children and adolescents. A slight male predominance has been consistently observed in childhood RMS.
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In most cases of childhood STS, no predisposing condition or exogenous exposures can be identified. Radiation-induced sarcomas have been seen in survivors of the Hiroshima atomic bomb blast and in childhood cancer survivors treated with radiotherapy. Exposure to chlorophenols and dioxin is associated with a greater risk of STS. Chronic lymphedema has been identified as a risk factor for lymphangiosarcoma. In children with acquired immunodeficiency syndrome (AIDS), leiomyosarcoma occurs at greater than background levels; Epstein-Barr viral infection is thought to play a causal role in the development of this cancer in immunocompromised patients.
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Rarely, STS occurs as part of recognizable genetic syndromes, either as an inherited gene in an affected family or as a new germline mutation. Li-Fraumeni syndrome is characterized by susceptibility to many cancers, including soft tissue and bone sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, and is associated with germline TP53 mutations. Soft tissue sarcoma occurs as a secondary tumor in patients with germline RB1 mutation, often presenting in or near the radiation field following treatment of a primary retinoblastoma. The lifetime risk of malignant peripheral nerve sheath tumor in patients with neurofibromatosis type 1 is approximately 10%; these patients also develop other STS including RMS. Desmoid fibromatosis has been reported to develop in about 10% of patients with familial adenomatous polyposis. Rhabdomyosarcoma occurs at a high rate in children with Costello syndrome, where it appears to be caused by germline HRAS mutations. Various STSs have also been reported in Beckwith-Wiedemann, Gorlin, hereditary multiple osteochondroma, Werner, and Rubinstein-Taybi syndromes.
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CLINICAL MANIFESTATIONS
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