GI Synovial Sarcomas

Synovial sarcoma accounts for about 10% of adult soft tissue sarcomas, with 80–90% located in the limbs. Gastrointestinal tract involvement is rare. Synovial sarcoma has a propensity for local recurrence and lung metastases, which can be delayed beyond 5 years. The t(X;18) translocation resulting in the expression of a SYT–SSX fusion protein is commonly seen. Demonstration of this type of genetic rearrangement by fluorescence in situ hybridization or PCR is fundamental to the diagnosis of synovial sarcoma in unusual sites. Owing to the rarity of this tumor in the gastrointestinal tract, the appropriate method and extent of surgical resection is uncertain.

We encountered a 44-year-old woman who underwent a gastroscopy for the diagnosis of melaena and epigastric pain. A 2-cm ulcerated polypoidal lesion on the proximal lesser curve was found, and a computerized tomographic scan of the abdomen and pelvis confirmed an ulcerated polypoidal mass in the proximal stomach with a maximum diameter of 4.7 cm. A computerized tomographic abdomen and pelvis done 14 months prior was reported as normal, however, in retrospect a 2.2-cm mass was noticeable. A laparoscopic wedge excision of the lesion was undertaken for presumed gastrointestinal stromal tumor (GIST). Histology showed a malignant spindle cell tumor arising in the stomach wall involving the muscularis propria, with extension into the mucosa and subserosal connective tissue, but not breaching the serosal mesothelium. The tumor had an extensive infiltrative nature, extending beyond the macroscopically defined tumor. The tumor was positive for CD99 and focal keratin (AE1/AE3 and CK7) but there was no KIT immunoreactivity detected. Re-arrangement in the SYT region was detected by fluorescence in situ hybridization, consistent with monophasic synovial sarcoma. Subsequently a wider excision of the tumor site was performed via an upper midline laparotomy. The patient remains well 40 months after the second operation. Upper endoscopy at 24 months, and computerized tomographic scan of the chest and abdomen 5 years after surgery show no evidence of recurrence.

In all, 10–20% of synovial sarcomas involve the head, neck, chest, or abdomen. Most abdominal tumors involve the body wall or retroperitoneum. Visceral involvement is rare but has been described in the gastrointestinal tract as well as the head and neck, mediastinum, heart, kidney, prostate, and vulva. Most case reports for gastrointestinal synovial sarcomas focus on pathological aspects. Follow-up was usually limited, and little detail was given regarding nature of the surgery or patterns of recurrence. This makes conclusions about the most appropriate form of treatment difficult. The behavior of synovial sarcomas of other sites may be relevant.

The overall survival for patients with localized primary synovial sarcoma is 61% at 5 years and 42% at 10 years in large series of predominantly limb tumors.¹ Late presentation of local and distant metastases is well recognized. Tumor size has consistently been shown to be an important prognostic feature with tumors <5 cm having improved survival. Patient age, tumor location, grade, mitotic activity, bone, or neurovascular invasion and SYT–SSX fusion type have variably been shown to be independent predictors of survival. A total of 12 synovial sarcomas of the stomach have been reported, 10 of which had follow-up of varying length.^{2, 3} One 16 cm tumor had multiple liver metastases at presentation. Recurrence was reported in one of the five cases <4 cm in size, with this tumor having a poorly differentiated component. Recurrence was seen in three of four tumors 4 cm or greater in size. Synovial sarcoma has a propensity to local recurrence particularly when excised without a margin of macroscopically normal tissue. In a series of synovial sarcomas assessed at the Royal Marsden Hospital Sarcoma Unit, a local recurrence rate of 74% was seen following marginal excision or enucleation without description of margins, 55% following excision with microscopically involved margins, and 18% following excision with microscopic margins free of tumor.⁴ In the series described by Bergh et al.⁵, the majority of patients who developed local recurrence had marginal or intralesional excisions in hospitals, which were not musculoskeletal tumor centers.

The most common site of metastases reported in series of synovial sarcomas from all sites is the lung. Previous retrospective studies have suggested that synovial sarcomas have a higher rate of nodal involvement than other sarcomas. However, large prospective databases report lymph node metastases in 0–3.3%. Interestingly in Deshmukh et al.¹ series, the only patients with metastastatic disease who survived for >10 years, were the two with nodal metastases. In Makhlouf et al.² series of gastric synovial sarcomas, five patients were treated by segmental or wedge resection and five had partial gastrectomy. About four of eight patients with follow-up developed recurrence (one wedge resection and three partial gastrectomies). In two cases this was peritoneal disease and in the other cases the pattern of recurrence is not documented. Billings et al.³ describes two cases of synovial sarcoma involving the stomach both of which were treated by gastrectomy. One patient had multiple liver metastases at presentation and the other patient was disease free after 21 months of follow-up.

We are aware of the reports of synovial sarcoma of the esophagus (10 cases), duodenum (3 cases), 4 small bowel (2 cases), small bowel mesentery, ascending colonic mesentery, liver, gastrocolic ligament, and omentum. Lymph node metastases are not described in any of these reports. There is also limited information about patterns of recurrence as most case reports do not have follow-up. A case report of a 5-cm synovial sarcoma of the distal duodenum describes local recurrence 8 months after resection with clear margins and negative nodes.⁶ Eriksen et al.⁷ described a 4-cm synovial sarcoma of the ileum had an initial resection of 8 cm of small bowel. A subsequent resection of 45 cm of small bowel with resection to the root of the mesentery was performed. A 1-cm deposit of synovial sarcoma was identified in the mesentery adjacent to the previous anastomotic site but no tumor was found in 31 lymph nodes. There was no recurrence at 24 months. In another case report, intra-abdominal hemorrhage was found at the time of resection of a 10-cm tumor of the gastrocolic ligament. This patient had resection of peritoneal and wound recurrences on four occasions but was alive 6 years after diagnosis.⁸ A 7-cm intraluminal synovial sarcoma of the proximal esophagus was treated by local excision via a right cervical oesophagotomy. After 10 months a recurrence developed in the right sternocleidomastoid muscle and subcutaneous tissue. Excision of the recurrence with right radical neck dissection found no tumor in the 39 lymph nodes examined.⁹

It is important to distinguish synovial sarcomas from GIST. The large majority of GIST are diagnosed on the basis of c-KIT expression. Multiple studies have found synovial sarcomas are c-KIT negative on immunohistochemical examination. There should be an index of suspicion for synovial sarcomas in lesions that are weak or negative for c-KIT and the diagnostic X;18 translocation should be sought. Gastrointestinal synovial sarcomas may previously have been diagnosed as leimyosarcoma or GIST. Increased awareness of the condition and testing for SYT–SSX gene fusion is likely to lead to increased numbers of reported cases.

There are no prospective trials of chemotherapy in treatment of synovial sarcoma. The objective response, including complete response, has been seen with anthracycline–ifosfamide chemotherapy.⁴ This combination was associated with improved early disease-specific survival in a multivariate analysis.^{9, 10} Randomized trials have shown a reduction in local recurrence of high-grade limb sarcomas treated with adjuvant radiotherapy. However, radiation of abdominal sarcomas is limited by tissue toxicity. The only reports of radiation of gastrointestinal synovial sarcoma are for tumors of the cervical esophagus.

Owing to the rarity of gastrointestinal synovial sarcomas it is difficult to make recommendations regarding optimal treatment. Our case and the review of the literature support surgical resection as a curative treatment, bearing in mind that late recurrence is well documented for synovial sarcoma. Gastric synovial sarcomas should have a wider margin of excision than would be accepted for a GIST, due to the propensity for local recurrence. However, nodal spread is uncommon in synovial sarcoma with only peritoneal recurrence described in gastric tumors. Therefore, function preserving local excision is probably preferable to formal gastrectomy with node dissection where possible.

The authors declare no conflict of interest.