Practice Essentials
Synovial sarcoma (also referred to as synovial cell sarcoma) is one of the most common soft-tissue tumors in adolescents and young patients, with approximately one third of cases occurring in the first two decades of life. Mean age of patients at diagnosis is approximately 30 years.
Adjuvant chemotherapy and neoadjuvant chemotherapy have been proposed for patients with metastatic soft-tissue sarcomas, but chemotherapy in the treatment of synovial sarcoma has been controversial. Surgical excision is still the cornerstone of treatment. (See Treatment.) There are no contraindications for surgical treatment, which is potentially life-saving. There is, however, a relative contraindication for treating these patients in primary centers; early referral to tertiary centers for definitive treatment is preferred. Radiation therapy (RT) is usually required in addition to surgery.
Prognosis of this relatively rare tumor is related to initial care. Survival rates have improved in the past 20 years because of treatment with primary radical surgery, along with chemotherapy and RT. [1, 2, 3, 4]
Pathophysiology
The origin of synovial sarcoma is unclear. Its name notwithstanding, this sarcoma is not associated with synovial joints. The basis for the name synovial cell sarcoma was the similarity between cells of this tumor and primitive synoviocytes.
A neurologic origin for this sarcoma has been suggested. In fact, there is a histologic resemblance between the neural cells of malignant peripherical nerve sheath tumor (MPNST) and the cells of synovial sarcoma. [5] Typically, synovial sarcoma is associated with a history of a long-standing nodule, sometimes present for years, which increases rapidly in size over a few months; consequently, it is sometimes overlooked. The tumor spreads along fascial planes and thus can be much more widespread than it appears on initial evaluation.
The (X;18)(p11;q11) translocation fuses the SYT gene from chromosome 18 to a homologous gene at Xp11 (SSX1, SSX2, or SSX4). The fusion proteins SYT-SSX1 and SYT-SSX2 are believed to function as aberrant transcriptional regulators, resulting in either activation of proto-oncogenes or inhibition of tumor suppressor genes.
A correlation appears to exist between the histologic subtype of the tumor and either of these two fusion proteins. Biphasic tumors, containing both epithelial and spindle cell components, express the SYT-SSX1 transcript, whereas monophasic tumors with only a spindle cell component may express either transcript. [5, 6, 7, 8, 9]
Etiology
Synovial sarcoma is characterized by a specific chromosomal translocation, t(X;18)(p11;q11). [10] This defect appears to be the underlying cause of the tumor. This specific chromosomal translocation between chromosome X and chromosome 18 has been noted in more than 90% of cases. This fusion gene is called, in genetic terms, the SYT-SSX1, SYT-SSX2, or SYT-SSX4. These terms correspond to a fusion of the SYT gene (chromosome 18) with the SSX gene (chromosome X).
Females are more commonly affected than males in both SYT-SSX2 and SYT-SSX1 types. This association is stronger in SYT-SSX2. To our knowledge, the origin of this translocation has not been identified. [5, 6, 7, 8, 9, 11]
Epidemiology
The incidence of synovial sarcoma has been estimated to be 2.75 per 100,000. [12] The majority of cases involve the lower extremities. Approximately 800 new cases occur in the United States each year, and this tumor represents around 5-10% of all soft-tissue sarcomas. Synovial sarcoma is the third most common soft-tissue tumor in adolescents and young adults. [13]
Prognosis
Synovial sarcoma has been reported to be particularly likely to metastasize. [14] Many factors modify patient outcome, [8, 15, 16, 17] such as tumor size, [18] anatomic localization, and histologic grade. Nevertheless, histologic criteria such as nuclear grade, measures of mitotic count, and amount of necrosis are subjective and sometimes difficult to compare.
Survival analysis is correlated with the location of the tumor in three anatomic regions:
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Trunk - Head, [19] neck, thorax, abdomen, and pelvis
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Distal extremity - Hands, feet, and ankles
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Proximal extremity - Arms, forearms, thighs, and legs
Distal-extremity tumors have a better prognosis than proximal-extremity or truncal tumors do. [12] Nevertheless, this malignancy can affect any part of the appendicular skeleton.
Synovial sarcoma has survival rates of 50-60% at 5 years and 40-50% at 10 years. However, advances in oncologic therapy, particularly the development of monoclonal antibodies, may improve survival rates.
A slight improvement in survival rate has been reported with the use of chemotherapy as adjuvant therapy. [13, 2, 3] Recurrence has been reported up to 69 months after treatment and suggests a worse prognosis with low survival rates. Distant metastases at presentation suggests a bad prognosis (2-year survival rate, 25%).
A study of 130 cases of synovial sarcoma treated by a single surgeon reported a global survival rate of 82% at the latest follow-up. [20] The local recurrence rate was 19%. In all, 28% of patients were diagnosed with at least a metastasis during follow-up; those with tumors larger than 5 cm were at significantly higher risk for metastasis.
Campbell et al described prognostic factors that correlated with a better prognosis, including the following [21] :
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Biphasic histologic pattern
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Patients with SYT/SSX2 fusion genes
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Location in the hand or foot
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Size < 5 cm
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Female sex
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Age < 50 years
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Negative resection margins
Crowson et al conducted a retrospective review of medical records to determine clinical and pathologic factors affecting survival in primary synovial cell sarcoma of the head and neck. [22] The study included 28 patients who underwent surgery for the removal of the primary lesion, of whom nine received adjuvant RT, two received chemotherapy, and 14 received postoperative chemoradiation therapy. The presence of metastases on initial presentation and tumor size exceeding 4 cm were found to be factors associated with decreased survival. [22] The addition of chemotherapy to postoperative RT was not found to improve survival or disease control.
In a study using data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute (NCI), Aytekin et al found that in a study group of 3228 patients (mean age, 39.3 ± 18.8 y; 47.1% female, 52.9% male) factors associated with a poorer prognosis were male sex, being a person of color, age greater than 35 years at the time of diagnosis, epithelioid type, and localization outside the head and neck region. [23] RT improved survival, but the benefit of chemotherapy was unclear.
The French Sarcoma Group (FSG) assessed outcomes in 417 patients with metastatic synovial sarcoma, either synchronous (n = 79; cohort 1) or metachronous (n = 338; cohort 2). [24] In cohort 1, independent favorable prognostic factors for overall survival were young age, surgery of the primary tumor, and a single metastatic site; in cohort 2, independent favorable prognostic factors were surgery within an expert FSG center, absence of perioperative chemotherapy, the lungs as a single metastatic site, time to first metastasis greater than 12 months, local therapy, and ifosfamide in the first metastatic line.
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Lateral radiograph depicts a synovial sarcoma of the dorsum of the hand. A small nodule, present for 5 years, rapidly enlarged to the present size over 2 months.
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T1-weighted MRI depicts a synovial sarcoma of the dorsum of the hand. The tumor has low signal on T1 weighting.
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T2-weighted MRI depicts a synovial sarcoma of the dorsum of the hand. The tumor has a heterogeneous signal on T2 weighting, indicative of a variable growth pattern.
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Although synovial sarcoma typically has a biphasic histology, this disease is often monophasic (lacking glandular differentiation), which produces the picture of a small, round blue cell tumor.
