Childhood Soft Tissue Sarcoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information

Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, pediatric radiation oncologist, pediatric hematologist/oncologist, rehabilitation specialist, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[1] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.


Pediatric soft tissue sarcomas (STSs) are a heterogenous group of malignant tumors that originate from primitive mesenchymal tissue and account for 7% of all childhood tumors.[3] Multidisciplinary evaluation in centers that have surgical and radiotherapeutic expertise is of critical importance to ensure the best clinical outcome for these patients. Although surgery with or without radiation therapy can be curative for a significant proportion of patients, the addition of chemotherapy might benefit subsets of children with the disease; therefore, enrollment into clinical trials is encouraged.


Rhabdomyosarcoma, a tumor of striated muscle, is the most common STS in children aged 0 to 14 years and accounts for 50% of tumors in this age group.[4] (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.) The remaining STSs are commonly referred to as nonrhabdomyosarcomatous STSs and account for about 3% of all childhood tumors.[5] This heterogeneous group of tumors includes neoplasms of:[6]

  • Connective tissue (e.g., desmoid fibromatosis, liposarcoma).
  • Peripheral nervous system (e.g., malignant peripheral nerve sheath tumor).
  • Smooth muscle (e.g., leiomyosarcoma).
  • Vascular tissue (blood and lymphatic vessels, e.g., angiosarcoma).

In children, synovial sarcoma, fibrosarcoma, fibrohistiocytic tumors, and malignant peripheral nerve sheath tumors predominate.[7,8] The distribution of STSs by histology and age, based on the Surveillance Epidemiology and End Results (SEER) information from 1975 to 2008, is depicted in Table 1. The distribution of histologic types by age is shown in Figure 1.

Table 1. Age Distribution of Soft Tissue Sarcomas (STSs) in Children Aged 0 to 19 Years (SEER 1975-2008)

Age <5 y Age 5-9 y Age 10-14 y Age 15-19 y % of the Total Number of STS Cases <20 y
pPNET = peripheral primitive neuroectodermal tumors; SEER = Surveillance Epidemiology and End Results.
a Dermatofibrosarcoma accounts for 75% of these cases.
All soft tissue and other extraosseous sarcomas 1,130 810 1,144 1,573 100
Rhabdomyosarcomas 710 466 364 350 41
Fibrosarcomas, peripheral nerve, and other fibrous neoplasms 151 64 132 192 12
Fibroblastic and myofibroblastic tumors 131 31 57 86 6.5
Nerve sheath tumors 19 32 74 104 5
Other fibromatous neoplasms 1 1 1 2 0.1
Kaposi sarcoma 1 2 0 12 0.3
Other specified soft tissue sarcomas 198 220 512 856 38
Ewing tumor and Askin tumor of soft tissue 22 28 57 81 4
pPNET of soft tissue 21 19 29 42 2.4
Extrarenal rhabdoid tumor 37 3 8 3 1
Liposarcomas 5 6 22 66 2
Fibrohistiocytic tumors a 53 69 171 293 12
Leiomyosarcomas 13 19 22 57 2.4
Synovial sarcomas 12 39 133 204 8.3
Blood vessel tumors 15 7 11 33 1.4
Osseous and chondromatous neoplasms of soft tissue 1 5 9 16 0.6
Alveolar soft parts sarcoma 3 7 19 26 1
Miscellaneous soft tissue sarcomas 16 18 31 35 2
Unspecified soft tissue sarcomas 70 58 136 163 9



Figure 1. The distribution of nonrhabdomyosarcomatous soft tissue sarcomas in children aged 0 to 19 years, as reported by the Surveillance Epidemiology and End Results program from 1975 to 2008.

Nonrhabdomyosarcomatous STSs are more common in adolescents and adults,[6] and most of the information regarding treatment and natural history of the disease in younger patients has been based on adult studies.

Risk Factors

Some genetic and environmental factors have been associated with the development of nonrhabdomyosarcomatous STS:

  • Genetic factors:
    • Li-Fraumeni syndrome: Patients with Li-Fraumeni syndrome (usually due to heritable cancer-associated changes of the p53 tumor suppressor gene) have an increased risk of developing soft tissue tumors (mostly nonrhabdomyosarcomatous STSs), bone sarcomas, breast cancer, brain tumors, and acute leukemia.[5,9]
    • Neurofibromatosis type 1: Approximately 4% of patients with neurofibromatosis type 1 develop malignant peripheral nerve sheath tumors, which usually develop after a long latency; some patients develop multiple lesions.[10,11,12]
    • Familial adenomatous polyposis: Patients with familial adenomatous polyposis are at increased risk of developing desmoid tumors.[13]
    • Werner syndrome: Werner syndrome is characterized by spontaneous chromosomal instability, resulting in increased susceptibility to cancer and premature aging. An excess of STSs has been reported in patients with Werner syndrome.[14]
    • Retinoblastoma gene: Germline mutations of the retinoblastoma gene have been associated with an increased risk of developing STSs, particularly leiomyosarcoma.[15]
  • Environmental factors:
    • Radiation: Some nonrhabdomyosarcomatous STSs (particularly malignant fibrous histiocytoma) can develop within a previously irradiated site.[5,16]
    • Epstein-Barr virus infection in patients with AIDS: Some nonrhabdomyosarcomatous STSs (e.g., leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients with AIDS.[5,17]

Clinical Presentation

Although nonrhabdomyosarcomatous STSs can develop in any part of the body, they arise most commonly in the trunk and extremities.[7,18,19] These neoplasms can present initially as an asymptomatic solid mass, or they may be symptomatic because of local invasion of adjacent anatomical structures.

Systemic symptoms (e.g., fever, weight loss, and night sweats) are rare. Hypoglycemia and hypophosphatemic rickets have been reported in cases of hemangiopericytoma, whereas hyperglycemia has been noted in patients with fibrosarcoma of the lung.[20]



When a suspicious lesion is identified, it is crucial that a complete workup, followed by adequate biopsy be performed. Generally, it is better to image the lesion before any interventions. Plain films can be used to rule out bone involvement and detect calcifications that may be seen in soft tissue tumors such as extraskeletal osteosarcoma or synovial sarcoma. Chest radiography and computed tomography (CT) of chest are essential to assess the presence of metastases. CT can be used to image intra-abdominal tumors, such as liposarcoma, and magnetic resonance imaging (MRI) can be used for extremity lesions.

Nonrhabdomyosarcomatous soft tissue tumors are fairly readily distinguished pathologically from rhabdomyosarcoma and Ewing sarcoma; however, classification of childhood nonrhabdomyosarcomatous STS type is often difficult. A core-needle biopsy or small incisional biopsy that obtains adequate tumor tissue is crucial to allow for conventional histology, immunocytochemical analysis, and other studies such as light and electron microscopy, cytogenetics, fluorescence in situ hybridization, and molecular pathology,[21,22] given the diagnostic importance of translocations. Needle biopsy techniques must obtain an adequate tissue sample and usually require obtaining multiple cores of tissue. Image guidance using ultrasound, CT scan, or MRI may be necessary to ensure a representative biopsy.[23] Incisional biopsies are acceptable but should not compromise subsequent wide local excision, and excisional biopsy of the lesion must be avoided. Transverse extremity incisions should be avoided to reduce skin loss, as should extensive surgical procedures before definitive diagnosis. For these reasons, open biopsy or multiple core-needle biopsies are strongly encouraged so that adequate tumor tissue can be obtained to allow for crucial studies to be performed and to avoid limiting future treatment options.

A single-institution analysis of adolescents and adults compared patients with unplanned excision of STS to stage-matched controls. In this retrospective analysis, unplanned initial excision of STS resulted in increased risk for local recurrence, metastasis, and death, and this increase was greatest for high-grade tumors.[24][Level of evidence: 3iiA]

Many nonrhabdomyosarcomatous STSs are characterized by chromosomal abnormalities. Some of these chromosomal translocations lead to a fusion of two disparate genes. The resulting fusion transcript can be readily detected by using polymerase chain reaction-based techniques, thus facilitating the diagnosis of those neoplasms that have translocations. Some of the most frequent aberrations seen in nonrhabdomyosarcomatous soft tissue tumors are listed in Table 2.


Table 2. Frequent Chromosomal Aberrations Seen in Nonrhabdomyosarcomatous STSa

Histology Chromosomal Aberrations Genes Involved
STS = soft tissue sarcoma.
a Adapted from Sandberg,[25]Slater et al.,[26]Mertens et al.,[27]and Romeo.[28]
Alveolar soft part sarcoma t(x;17)(p11.2;q25) ASPL/TFE3[29,30,31]
Angiomatoid fibrous histiocytoma t(12;16)(q13;p11), t(2;22)(q33;q12), t(12;22)(q13;q12) FUS/ATF1,EWSR1/CREB1,[32]EWS/ATF1
Clear cell sarcoma t(12;22)(q13;q12), t(2;22)(q33;q12) ATF1/EWS,EWSR1/CREB1
Congenital (infantile) fibrosarcoma/mesoblastic nephroma t(12;15)(p13,q25) ETV-NTRK3
Dermatofibrosarcoma protuberans t(17;22)(q22;q13) COL1A1/PDGFB
Desmoid fibromatosis Trisomy 8 or 20, loss of 5q21 CTNNB1orAPCmutations
Desmoplastic small round cell tumors t(11;22)(p13;q12) EWS/WT1[33]
Epithelioid hemangioendothelioma t(1;3)(p36;q25)[34] WWTR1/CAMTA1
Epithelioid sarcoma Inactivation SMARCB1 SMARCB1
Extraskeletal myxoid chondrosarcoma t(9;22)(q22;q12), t(9:17)(q22;q11), t(9;15)(q22;q21), t(3;9)(q11;q22) EWSR1/NR4A3,TAF2N/NR4A3,TCF12/NR4A3,TGF/NR4A3
Hemangiopericytoma t(12;19)(q13;q13.3) and t(13;22)(q22;q13.3)
Inflammatory myofibroblastic tumor t(1;2)(q23;q23), t(2;19)(q23;q13), t(2;17)(q23;q23), t(2;2)(p23;q13), t(2;11)(p23;p15)[35] TPM3/ALK,TPM4/ALK,CLTC/ALK,RANBP2/ALK,CARS/ALK
Low-grade fibromyxoid sarcoma t(7;16)(q33;p11), t(11;16)(p11;p11) FUS/CREB3L2,FUS/CREB3L1
Malignant peripheral nerve sheath tumor 17q11.2, loss or rearrangement 10p, 11q, 17q, 22q NF1
Myxoid/round cell liposarcoma t(12;16)(q13;p11), t(12;22)(q13;q12) FUS/DD1T3,EWSR/DD1T3
Rhabdoid tumor Inactivation SMARCB1 SMARCB1
Synovial sarcoma t(x;18)(p11.2;q11.2) SYT/SSX
Tenosynovial giant cell tumor t(1;2)(p13;q35) CSF1


The prognosis of nonrhabdomyosarcomatous STS tumors varies greatly depending on the histologic grade, invasiveness, tumor size, resectability, use of radiation therapy, site of primary tumor, and presence of metastases.[36,37,38] Some pediatric nonrhabdomyosarcomatous STSs are associated with a better outcome. For instance, infantile fibrosarcoma, presenting in infants and children younger than 4 years, has an excellent prognosis given that the tumor is highly chemosensitive and surgery alone can cure a significant number of these patients.[5]


Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients.[5,21]

Pediatric patients with unresected localized nonrhabdomyosarcomatous STSs have a poor outcome. Only about one-third of patients treated with multimodality therapy remain disease free.[36,39]; [40,41][Level of evidence: 3iiiA]

In a pooled analysis from U.S. and European pediatric centers, outcome was better for patients who received radiation therapy than for patients who did not, and outcome was better for patients whose tumor-removal procedure was deemed complete than for patients whose tumor removal was incomplete.[40][Level of evidence: 3iiiA]

Because long-term related morbidity must be minimized while disease-free survival is maximized, the ideal therapy for each patient must be carefully and individually determined utilizing these prognostic factors before initiating therapy for these patients.[18,42,43,44,45,46]

Related Disease Summaries

Refer to the following PDQ summaries for information about other types of sarcoma:

  • Childhood Rhabdomyosarcoma Treatment.
  • Ewing Sarcoma Treatment (extraosseous Ewing, peripheral neuroepithelioma, and Askin tumors).
  • Unusual Cancers of Childhood Treatment (gastrointestinal stromal tumors).
  • Adult Soft Tissue Sarcoma Treatment.


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