Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor
(Refer to the PDQ summary on Ewing Sarcoma Treatment for more information.)
Synovial sarcoma is one of the most common nonrhabdomyosarcomatous STSs in children and adolescents. In a Surveillance Epidemiology and End Results review from 1973 to 2005, 1,268 patients with synovial sarcoma were identified. Approximately 17% of these patients were children and adolescents and the median age at diagnosis was 34 years. The most common location is the extremities, followed by trunk and head and neck. Patients younger than 10 years have more favorable outcomes and clinical features, including extremity primaries, smaller tumors, and localized disease, than do older patients.
Synovial sarcoma can be subclassified as the following types:
- Monophasic fibrous type.
- Biphasic type with distinct epithelial and spindle cell components.
- Poorly differentiated. Poorly differentiated synovial sarcoma has features of monophasic or biphasic synovial sarcoma but also has a variable proportion of poorly differentiated areas characterized by high cellularity, pleomorphism, and polygonal or small round-cell morphology, numerous mitoses, and often necrosis.
The diagnosis of synovial sarcoma is made by immunohistochemical analysis, ultrastructural findings, and demonstration of the specific chromosomal translocation t(x;18)(p11.2;q11.2). This abnormality is specific for synovial sarcoma and is found in all morphologic subtypes. Synovial sarcoma results in rearrangement of the SYT gene on chromosome 18 with one of the subtypes (1, 2, or 4) of the SSX gene on chromosome X.[123,124] It is thought that the SYT/SSX18 transcript promotes epigenetic silencing of key tumor suppressor genes.
The most common site of metastasis is the lung.[126,127] The risk of metastases is highly influenced by tumor size; it is estimated that patients with tumors that measure greater than 5 cm have a 32-fold risk of developing metastases when compared with other patients.
In a retrospective analysis of synovial sarcoma in children and adolescents who were treated in Germany and Italy, tumor size (>5 cm or ≤5 cm in greatest dimension) was an important predictor of EFS. In this analysis, local invasiveness conferred an inferior probability of EFS, but surgical margins were not associated with clinical outcome. A multicenter analysis of 219 children from various treating centers including Germany, SJCRH, Instituto Tumori, and MD Anderson Cancer Center reported an estimated 5-year OS of 80% and EFS rate of 72%. In this analysis, an interaction between tumor size and invasiveness was observed; in multivariate analysis, patients with large or invasive tumors or with Intergroup Rhabdomyosarcoma Study (IRS) Clinical Group III and IV disease had decreased OS. Treatment with radiation therapy was related to improved OS (hazard ratio, 0.4; 95% confidence interval, 0.2–0.7). In IRS Group III patients, objective response to chemotherapy (18 of 30 [60%]) correlated with improved survival. In adults, factors such as International Union Against Cancer/American Joint Committee on Cancer stage III and stage IVA, tumor necrosis, truncal location, elevated mitotic rate, age, and histologic grade have been associated with a worse prognosis.[129,130,131]