Synovial sarcoma (SS) is typically an aggressive malignant soft tissue tumor that mostly affects adolescents and young adults. It is extremely rare in orbit and carries a high risk of recurrence and metastasis, posing a challenge to ophthalmologists in diagnosing and managing. We present two primary orbital synovial sarcoma cases with unilateral exophthalmos and limited motility. Both male patients underwent reoperation in our hospital since tumor recurrence; the pathologic diagnoses were biphasic type and occult type, respectively. Both cases were positive for EMA and CK, and SOX-9 and INI-1 were newly discovered immune markers.
Synovial sarcoma (SS) is a highly malignant soft tissue sarcoma that differentiates into mesenchymal tissue and epithelium. It accounts for approximately 10% of all soft tissue tumors and has an unknown source and cell of origin, variable clinical behavior, and unique genetic features [
Two cases of orbital SS have been reviewed, which were accessioned in the database of the Ophthalmology Department and Pathology Department of West China Hospital of Sichuan University from 2009 to 2021.
A 56-year-old man presented with a 2-year history of proptosis of the right eye (
A 28-year-old man sought treatment for tumor recurrence of the right orbit. Three years and eight months ago, he underwent two operations and adjuvant radiation in another hospital. The pathologic diagnosis was mesenchymal chondrosarcoma. His best corrected visual acuity was 20/20 in both eyes, and the right eye showed an obvious proptosis with limited motility in horizontal directions. The remainders of the ophthalmic examination results were normal. An orbital CT scan revealed a right retrobulbar soft mass near the lateral wall with calcification and bone involvement (
Orbital SS is a very rare malignant entity. Among the 13 current reports of orbital SS (including our cases), 11 were primary SS (
SS is categorized into 3 main types: the monophasic type contains only spindle cells, the biphasic type contains epithelial and spindle cell components in varying proportions, and the poorly differentiated type contains monophasic and biphasic regions as well as poorly differentiated areas [
As observed in case 2, SS is commonly missed or misdiagnosed; the patient was initially considered to have mesenchymal chondrosarcoma. The pathologic differential diagnosis of SS includes malignant peripheral nerve sheath tumor, fibrosarcoma, leiomyosarcoma, mesenchymal chondrosarcoma and other small round blue cell tumors. Traditionally, the diagnosis of biphasic SS depends on its unique histological morphology, but other types need to be supported by immunohistochemical and molecular genetic studies.
Positivity for EMA, CK, and Vimentin is the most valuable and sensitive marker for the diagnosis of SS. TLE-1 is highly sensitive but not specific to SS [
SS carries a high risk of local recurrence and distant metastasis that most often occur in the lungs, brain, lymph, and bone marrow [
Surgical resection with a negative margin remains the standard initial treatment for SS; however, it is difficult to obtain negative surgical margins due to the poorly defined form of the tumor and its adherence to critical issues such as the extraocular muscles or optic nerve. Exenteration could be considered if the tumor is large or if tumor-free margins are difficult to identify. Postoperative radiotherapy is recommended for patients with positive margins to prevent tumor relapse or metastasis. Palmerini et al. [
Orbital SS is extremely rare and easily misdiagnosed. The diagnosis should be made by combining histopathology, immunohistochemistry, and molecular genetics. SS18-SSX fusion gene testing is the golden standard of diagnosis, however, due to the current high cost, high equipment requirements and failure to detect SS18-SSX in a few SS cases, exploring more economical and effective methods for SS identification is still necessary. Patients with orbital SS need to be treated with free-marginal surgery combined with adjuvant radiotherapy or chemotherapy, the latter should be added for high-risk SS or metastasis SS. However, we also need further studies to explore new immunotherapy and gene therapy to improve the survival rate.
The authors thank the patients who agreed to be included in this study.
YW: Conceptualization, methodology, data collection, writing original draft and review and editing, YJW: Investigation, review and editing, WMH: Surgery, conceptualization, supervision, review and editing.
Informed written consent has been obtained from the patients in this case report to publish this paper. The present study involved human participants, and it was conducted considering ethical responsibilities according to the World Medical Association and the Declaration of Helsinki.
There is no additional data regarding this study and all available data and materials have been shared within the case report.
The authors received no specific funding for this study.
The authors declare that they have no conflicts of interest to report regarding the present study.
Case | Author | Age sex | Clinical history | Location | Imaging | Histopathology | Immune markers | Molecular genetics | Treatment | Follow-up |
---|---|---|---|---|---|---|---|---|---|---|
1 | Thomas et al. [ |
54,M | 7-year-history of painless exophthalmia | Right orbit and posterosuperior | - | Biphasic | - | - | RT to decrease exophthalmia; |
No recurrences and metastasis after 4 years |
2 | Ratnatunga et al. [ |
21, F | 5-year-history of painless mass with the displacement of the eyeball and limited adduction | Left orbit: subconjunctival mass, adherent to the medial rectus muscle and extending posteriorly into the retrobulbar region | - | Biphasic | EMA, pankeratin | - | Incomplete excision | - |
3 | 42, F | 8-month-history of swelling | Left orbit: adherent to the tendon sheath of the superior oblique muscle | - | Biphasic | EMA, pankeratin | - | Incomplete excision | - | |
4 | Shukla et al. [ |
32, F | 5-year-history of recurrent swelling and pain, diplopia, and decreased vision, motility restriction | Left orbit: encroaching the cornea | CT: 4 × 2.5cm well-defined enhancing mass with calcifications, involving the globe, and the medial, lateral, and superior recti muscles | Biphasic | pan-cytokeratin, EMA, |
- | Incomplete excision; |
- |
5 | Hartstein et al. [ |
14,M | 1-month-history of painless proptosis | Left orbit | CT: well-circumscribed intraconal mass | Biphasic | vimentin, collagen IV, |
t (X; 18) | Exenteration | No recurrences after 18 months |
6 | Kusuma et al. [ |
18, F | 18-month-history of a slowly enlarging mass | Right medial canthus | CT: mass extended into the right lateral nasal dorsum | Monophasic | vimentin, EMA; |
- | Complete excision; |
No recurrences after 7 years |
7 | Liu et al. [ |
1.5, F | 1-month-history of painless swelling in left eyelid, proptosis, inflamed conjunctiva, and limited ocular motility | Left upper eyelid, nasal portion, adherent to the medial rectus muscle | CT: orbital mass with unclear border | Poorly differentiated | pan cytokeratin, EMA, |
t (X; 18) | Orbitotomy with |
No recurrences and metastasis after 1 year |
8 | Stagner et al. [ |
31, F | Fullness in her temporal left lower eyelid, left facial, orbital and periorbital pain for more than a decade; proptosis, upward displacement of the globe, and eyelid ptosis | Left inferior orbit, adherent to the inferior rectus and oblique muscles | CT and MRI:2.5 × 1.5 × 2.8 cm well-defined mass with calcifications, adherence to the inferior rectus and oblique muscles | Poorly differentiated | TLE1, CD99, EMA, |
t (X; 18) | Subtotal excision; |
No recurrences after 6 months |
9 | Xu et al. [ |
6, F | 1-week-history of painless proptosis, motility restriction | Right orbit | CT and MRI: 4 × 5.5 × 6.5 cm mass in the lateral orbital wall extending into the orbit, the intracranial, and the temporal fossa, with bone destruction | Monophasic | vimentin, CD99, |
- | Complete excision; |
No recurrences and metastasis after 1 year |
10 | Portelli et al. [ |
24, F | 1-year-history of painful cystic lesion | Left superonasal orbit | B ultrasound:1.4 × 0.75 cm hypoechogenic uniform roundish lesion | Monophasic | EMA, AE1/AE3, |
t (X; 18) | Complete excision | No recurrences and metastasis after 20 months |
11 | Gervasio et al. [ |
23, F | 1-year-history of right upper eyelid mass, pain, headache, eyelid swelling, right upper eyelid ptosis | right superomedial orbit | CT: 2 × 1.5 × 1 cm, well-circumscribed, extraconal, |
Monophasic | TLE-1,EMA,S-100,SOX10,Ki67 1%–15% | ss18 rearrangement | Complete excision; RT | under treatment |
1.Thomas, C., Guillemin, M. (1966). Typical primary synovial sarcoma of the orbit.
2.Ratnatunga, N., Goodlad, J. R., Sankarakumaran, N., Seimon, R., Nagendran, S. et al. (1992). Primary biphasic synovial sarcoma of the orbit.
3.Shukla, P. N., Pathy, S., Sen, S., Purohit, A., Julka, P. K. et al. (2003). Primary orbital calcified synovial sarcoma: A case report.
4.Hartstein, M. E., Silver, F. L., Ludwig, O. J., O’Connor, D. M. (2006). Primary synovial sarcoma.
5.Kusuma, S., Skarupa, D. J., Ely, K. A., Cmelak, A. J., Burkey, B. B. (2010). Synovial sarcoma of the head and neck: A review of its diagnosis and management and a report of a rare case of orbital involvement.
6.Liu, K., Duan, X., Yang, L., Yu, Y., Liu, B. (2012). Primary synovial sarcoma in the orbit.
7.Stagner, A. M., Jakobiec, F. A., Fay, A. (2017). Primary orbital synovial sarcoma: A clinicopathologic review with a differential diagnosis and discussion of molecular genetics.
8.Xu, P., Chen, J. (2017). Primary synovial sarcoma of the orbit.
9.Portelli, F., Pieretti, G., Santoro, N., Gorelli, G., de Giorgi, V. et al. (2019). Primary Orbital Synovial Sarcoma Mimicking a Periocular Cyst.
10.Gervasio, K. A., Ramesh, S., Sivalingam, M. D., Markovitz, M., Milman, T. (2021). Primary synovial sarcoma of the orbit: A case report and update on diagnostic techniques.