PDQ® Treatment Health Professionals
This treatment information summary on childhood soft tissue sarcoma is an overview of prognosis, diagnosis, classification, and treatment. The National Cancer Institute created the PDQ database to increase the availability of new treatment information and its use in treating patients. Information and references from the most recently published literature are included after review by pediatric oncology specialists.
Cancer in children and adolescents is rare. A team approach, incorporating the skills of the primary care physician, surgical specialists, radiation oncologist, pediatric hematologist/oncologist, rehabilitation specialist, pediatric nurse specialists, and social worker is imperative to ensure that patients receive treatment that will ensure optimal survival results. For advances to be made in treating these patients, therapy is best delivered in the context of a clinical trial at a major medical center with expertise in treating children. Only through entry of all eligible children into appropriate, well-designed clinical trials will progress be made against these diseases. 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.
Pediatric soft tissue sarcomas are a group of malignant tumors that originate from primitive mesenchymal tissue and account for 7% of all childhood tumors. Rhabdomyosarcomas, tumors of striated muscle, account for more than one half of all cases of soft tissue sarcomas in children. (See PDQ Rhabdomyosarcoma information summary) The remaining nonrhabdomyosarcomatous soft tissue sarcomas account for approximately 3% of all childhood tumors. This heterogeneous group of tumors includes neoplasms of smooth muscle (leiomyosarcoma), connective tissue (fibrous and adipose), vascular tissue (blood and lymphatic vessels), and the peripheral nervous system. These tumors are histologically classified according to the adult tissue they most resemble, and synovial sarcomas, fibrosarcomas, and neurofibrosarcomas predominate in pediatric patients.[5,6]
Nonrhabdomyosarcomatous soft tissue sarcomas are more common in adults (approximately 5,700 new cases each year) than in children; therefore, much of the information regarding the treatment and natural history of children with these lesions has been on the basis of findings from adult studies. However, pediatric nonrhabdomyosarcomatous soft tissue sarcomas are often associated with a better outcome. This difference is most pronounced for infants and young children (<4 years of age) with fibrosarcoma, whose tumors are locally aggressive but not metastatic; these patients have an excellent prognosis when treated with surgery only.[3,4,7] Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients.[3,4]
Although they can develop in any part of the body, nonrhabdomyosarcomatous soft tissue sarcomas arise most commonly in the trunk and extremities.[5,6] 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.
Genetic and environmental factors influence the development of nonrhabdomyosarcomatous soft tissue sarcomas. Heritable cancer-associated changes of the p53 tumor suppressor gene can occur in families with Li-Fraumeni syndrome. Members of these families have an increased risk of developing soft tissue tumors, bone sarcomas, breast cancer, brain tumors, and acute leukemia. 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.[4,9] Some nonrhabdomyosarcomatous soft tissue sarcomas (particularly malignant fibrous histiocytoma) can develop within a previously irradiated site; others (e.g., leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients with acquired immune deficiency syndrome.[3,4,10]
The treatment of rhabdomyosarcoma is covered in the treatment information summary on rhabdomyosarcoma. Extraosseous Ewing's, peripheral neuroepithelioma, and Askin's tumor are discussed in the treatment information summary on Ewing's sarcoma. Because the prognosis and biology of these tumors vary greatly depending on the age of the patient, the specific histology, the primary site, and the extent of disease, and because the 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. Studies have shown that tumor size, tumor invasiveness, histologic grade, and extent of disease at diagnosis influence outcome in pediatric patients with nonrhabdomyosarcomatous soft tissue sarcomas, and these prognostic factors should be weighed before initiating therapy for these patients.[6,11-13]
Pediatric soft tissue sarcomas are classified histologically according to the soft tissue cell they resemble and include the following.
tumors of fibrous tissue:
Table 1. Frequent aberrations seen in nonrhabdomyosarcomatous soft tissue tumors ------------------------------------------------------------------------------- Histology Chromosomal aberrations Genes involved ------------------------------------------------------------------------------- Infantile fibrosarcoma Trisomy 11; also +8, +17, +20 Neurofibrosarcoma Deletion 17q11.2 Malignant fibrous histiocytoma 19p+, ring chromosome Hemangiopericytoma t(12;19)(q13;q13.3) and t(13;22)(q22;q13.3) Alveolar soft part sarcoma 17q25 abnormalities Leiomyosarcoma t(12;14) Synovial sarcoma t(X;18)(p11.2;q11.2) SYT/SSX Clear cell sarcoma t(12;22)(q13-14;q12-13) ATF1/EWS Myxoid liposarcoma t(12;16)(q13;p11) FUS/CHOP
In the majority of cases, accurate histopathologic classification of soft tissue sarcomas does not yield optimal information about their clinical behavior. Therefore, several histologic parameters including degree of cellularity, cellular pleomorphism, mitotic activity, degree of necrosis, and invasive growth are evaluated in the process known as "grading." This process is used to improve the correlation between histologic findings and clinical outcome. In children, grading of soft tissue sarcomas is compromised by the good prognosis of certain tumors such as infantile fibrosarcoma. In addition, testing of a grading system within the pediatric population is difficult due to the rarity of these neoplasms. In March 1986, the Pediatric Oncology Group (POG) conducted a prospective study for pediatric soft tissue sarcomas other than rhabdomyosarcoma and devised the grading system that is shown below. Analysis of outcome for patients with localized soft tissue sarcomas other than rhabdomyosarcoma demonstrated that patients with grade 3 tumors fared significantly worse than did those with grade 1 or grade 2 lesions. This finding suggests that this system can accurately predict the clinical behavior of nonrhabdomyosarcomatous soft tissue tumors in children.[2,6]
Grade 1 lesions:
Clinical staging has an important role in predicting the clinical outcome and determining the most effective therapy for pediatric soft tissue sarcomas. As yet, there is no well-accepted staging system that is applicable to all childhood sarcomas; the system from the American Joint Commission for Cancer that is used for adults has not been validated in pediatric studies. Two systems are currently in use for staging pediatric nonrhabdomyosarcomatous soft tissue tumors. The surgicopathologic staging system used by the Intergroup Rhabdomyosarcoma Study (see below) is based on the amount of tumor that remains after initial surgery and on whether the disease has metastasized.
These two staging systems have proven to be of prognostic significance in pediatric and adult nonrhabdomyosarcomatous soft tissue sarcomas.[4-7] In a review of a large adult series of non-rhabdo sarcomas, superficial extremity sarcomas have a better prognosis than deep tumors. Thus, in addition to grade and size, the depth of invasion of the tumor should be considered.
Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas, all children, adolescents, and young adults with these tumors should have their treatment planned by a multidisciplinary team composed of pediatric oncologists, surgeons, and radiotherapists. To better define the natural history and response to therapy of these tumors, children with these rare neoplasms should be considered for entry into national or institutional treatment protocols.
Wide surgical resection of the primary tumor to yield negative margins remains the mainstay of therapy for pediatric soft tissue sarcomas other than rhabdomyosarcoma.[1,2] When there is concern about the adequacy of the surgical margin, radiation therapy is indicated  particularly in high grade tumors with tumor margins less than 1 cm. By using these two treatment modalities, local control of the primary tumor can be achieved in more than 80% of patients.
Therapeutic strategies for children and adolescents with soft tissue tumors are similar to those for adult patients, although there are important differences. For example, the biology of the pediatric form of the neoplasm may differ dramatically from that of the adult lesion. In addition, the morbidity of radiation therapy in young children may be much greater than that observed in adults, and limb-sparing procedures are more difficult to perform in pediatric patients. Further, the concern regarding potential long-term side effects of combined modality therapy (radiation, surgery, and chemotherapy) is greater for children, whose survival may be much longer than that of adults. Therefore, to maximize tumor control and minimize long-term morbidity, treatment must be individualized for children and adolescents with nonrhabdomyosarcomatous soft tissue tumors. These patients should be enrolled in prospective studies that accurately assess any potential complications.
The outcome for selected nonmetastatic pediatric soft tissue sarcomas is shown in Table 2.
Table 2. Outcome for selected nonmetastatic pediatric soft tissue sarcomas ------------------------------------------------------------------------------- Histologic Subtype Outcome ------------------------------------------------------------------------------- Infantile fibrosarcoma Excellent with surgery alone Adult-type fibrosarcoma Similar to that in adults (60%) Neurofibrosarcoma Stage-related: very good with complete excision; poor with incomplete excision Malignant fibrous histiocytoma Approximate survival 50% Angiomatoid variant Excellent with surgery alone Leiomyosarcoma Prognosis good for tumors arising outside the gastrointestinal tract but poor for those in the gastrointestinal tract Liposarcoma Good with complete resection Synovial sarcoma 80% survival for localized grossly or completely resected tumors Hemangiopericytoma Excellent in young children; 30% to 70% in older patients Alveolar soft part sarcoma 50% survival; late relapses are common Desmoid tumors Excellent survival; rarely metastasizes
A. Fibrosarcomas and hemangiopericytomas in infants and young children, desmoid tumors, and angiomatoid malignant fibrous histiocytomas typically are clinically less aggressive, rarely metastasize, and can be treated with surgery alone.
Desmoid tumors are well-differentiated fibrous lesions that rarely
metastasize but have a significant potential for local invasiveness and
recurrence. A surgical approach to clear margins is the treatment of
choice. When margins are positive, 70% of patients will have a recurrence
of disease. When complete surgical excision is not feasible and the tumor
poses significant potential for mortality or morbidity, preoperative
strategies that include external-beam radiation therapy, postoperative
interstitial iridium-192, nonsteroidal antiinflammatory agents,
antiestrogens, vinblastine, and methotrexate should be considered.
Partially excised or recurrent lesions that do not pose a significant danger
to vital organs may be monitored closely if other treatment alternatives are
The prognosis for children with metastatic soft tissue sarcomas is poor,[1-6] and these children should receive combined treatment with chemotherapy, radiation therapy, and surgical resection of pulmonary metastases. In a prospective randomized trial, chemotherapy with vincristine, dactinomycin, doxorubicin, and cyclophosphamide with or without dacarbazine led to tumor responses in one third of patients with unresectable or metastatic disease. However, the estimated 4-year survival rate was poor, with less than one third of children surviving.
With the possible exception of infants with congenital fibrosarcoma, the prognosis for patients with recurrent or progressive disease is poor. The selection of further treatment depends on many factors, including the site of recurrence, prior therapy, and individual patient considerations. Local recurrence or isolated pulmonary recurrence should be treated with complete surgical excision. All patients with recurrent tumors should be offered enrollment in current drug studies.