Synovial Sarcoma (Orbit)

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Disease Entity

Histopathology

The name "synovial sarcoma" is due to the histopathological similarities of the tumor with the developing synovium. However, in addition to synovial sarcoma having undifferentiated mesenchymal origin, it has no anatomical relationship with synovial structures.

Synovial sarcoma may present three histological types. The monophasic type is the most common and consists of spindle cells whereas the biphasic type has spindle and epithelial cells. The poorly differentiated type is composed of both monophasic and biphasic areas and additionally by poorly differentiated cells.[1] On the 8 tumors reported in literature, 5 were biphasic, 1 was monophasic fibrous, and 2 cases were poorly differentiated.[2] [3] [4] [5] [1][6] [7]

Epidemiology

Seven percent of malignant neoplasms in children are soft tissue sarcomas.[8] Although synovial sarcoma (SS) is the second most common soft tissue sarcoma in childhood (after rhabdomyosarcoma), it accounts for only 10% of all soft tissue sarcomas.[9][2] Synovial sarcoma (in all body locations) is more frequent in children and young adults, between 10-35 years of age and has no sex predominance. The main site of synovial sarcoma manifestation are the extremities, followed by the head and neck.[9][2][3]

Rarely, the orbit is affected by a primary synovial sarcoma, with only 8 previously reported cases.[2] [3] [4] [5] [1] [6] [7] In 8 reported cases the mean age of patients was 25.6 ± 12.0 years (range from 18 months to 42 years) and tumors occurred more commonly in the left orbit (6 cases) with a 3:1 female preponderance.3-9[2] [3] [4] [5] [1] [6] [7]

Synovial sarcoma usually presents as a well-defined lesion with calcification. However, the metastasis development occurs in 50% of cases and the lungs are the most frequently reached site, followed by lymph node and bone marrow.[2] [3] [4] [5] [1] [6]

Diagnosis

Symptoms and Clinical evaluation

The most characteristic presentation for primary orbital SS is the progressive onset of unilateral proptosis and periorbital pain worse on movement. Further, patients may present with a history of worsening eyelid edema and erythema, chemosis, ophthalmoplegia, blepharoptosis, or a palpable mass. Posteriorly located tumors are more commonly associated with choroidal folds, retinal detachment, retinal vessel tortuosity, and optic disc edema with optic neuropathy. Larger tumors are more likely to cause extraocular motility restriction, severe proptosis, and optic nerve compression.

Diagnosis consists of a detailed history, ocular examination, imaging studies including CT (Computer tomography) or MRI, and biopsy. Imaging is of particular importance in the diagnosis of orbital SS and subsequent management including surgical planning. Commonly, the tumor shows a calcification on CT. The presence of calcifications in tumour lesions is rare in other sarcomas such as rhabdomyosarcoma and in non-vascular orbital tumours.[6][10]

Genetics

Synovial sarcoma is strongly associated with a characteristic chromosomal translocation (X; 18) (p11.2;q11.2). This translocation can be found in 90% of all synovial sarcomas and in addition, it is absent in other types of sarcoma.[1]

The translocation results in the fusion of the SS18 (SYT) gene on chromosome 18 to one of the SSX genes (either SSX1 and SSX2) located on two subregions of chromosome Xp11 (23 and 21). The gene fusion products are SYT-SSX1 in 2/3 of cases or SYT- SSX2 in 1/3 of cases.[6] [7] [10]

The type of gene fusion is correlated with the histological type and prognosis. Fusion of the SYT and SSX1 genes is related to the biphasic histological type whereas the monophasic type is associated with the fusion of the SYT and SSX2 genes. The first type of fusion is associated to a worse prognosis.[2][6]

Management

General treatment

Patients with SS should be followed in oncologic consultation and perform systemic evaluation, including exhaustive blood tests, lumbar puncture, chest and abdominal CT, Positron Emission Tomography of of the head/neck/ abdomen/pelvis and Bone Scintigraphy.

In literature, two patients were treated solely with exenteration, three with total excision (with or without adjuvant RT or adjuvant chemotherapy) and three with sub-total excison (with or without adjuvant RT). Follow-up was available in only 4 cases (ranging from 6 mnonths-4 years) and none had a recurrence or metastasis emerged.[2] [3] [4] [5] [1] [6] [7]

The role of RT has not yet been fully established. On the one hand, it appears to increase overall survival and decrease recurrence rates in patients in whom total tumor excision (stage III of the Intergroup Rhabdomyosarcoma Study staging system) was not possible. On the other hand, it does not seem to play a role in the therapeutic approach if total excision of the tumor is possible.[2][6]

The role of systemic chemotherapy is well demonstrated in soft tissue sarcomas. Synovial sarcoma is more sensitive to chemotherapy than most childhood sarcomas, and therefore the therapeutic approach with Ifosfamide and Doxorubicin is the first treatment line.[6] [10] However, the role of chemotherapy as adjuvant therapy has not yet been established. It appears to be associated with better recurrence-free survival in adult soft tissue sarcomas (synovial and non-synovial sarcoma), but in the other hand, it has not shown benefit in children with grossly resected synovial sarcoma.[2]

In orbital synovial sarcoma, the surgical approach with exenteration may be a therapeutic option if the tumour is large or the tumour-free margins are difficult to delineate.[1]

Prognosis

The prognosis of synovial sarcoma seems to be better if the patient is younger than 10 years, the tumour is smaller than 5 cm and is located at the extremities, whereas a worse prognosis is associated with the occurrence of tumour necrosis and a location in the trunk or orofacial region.[6] The histological type is also related to the prognosis. The poorly differentiated type is associated with bigger rates of metastatic disease and is more aggressive.[5]

Synovial sarcoma (orbital and non-orbital location) presents a 5-year survival rate around 80% but decreases dramatically to 30% if relapse occurs.[6] [10]

Synovial sarcoma is a tumor whose orbital location is rare. Since there are only 8 cases described in the literature, the best therapeutic approach and the prognosis still remain to be clarified.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Liu K, Duan X, Yang L, Yu Y, Liu B. Primary synovial sarcoma in the orbit. J AAPOS. 2012;16:582-4.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Hartstein ME, Silver FL, Ludwig OJ, et al. Primary synovial sarcoma. Ophthalmology 2006;113:2093-6.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Thomas C, Guillermin M. Typical primary synovial sarcoma of the orbit [in French]. Doc Ophthalmol 1966;20:484-99.
  4. 4.0 4.1 4.2 4.3 4.4 5 Ratnatunga N, Goodlad JR, Sankarakumaran N, et al. Primary biphasic synovial sarcoma of the orbit. J Clin Pathol 1992;45:265-7.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 Shukla PN, Pathy S, Sen S, et al. Primary orbital calcified synovial sarcoma: A case report. Orbit 2003;22:299-303.
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 Stagner AM, Jakobiec FA, Fay A. Primary orbital synovial sarcoma: a clinicopathologic review with a differential diagnosis and discussion of molecular genetics. Surv Ophthalmol. 2016;62:227–236.
  7. 7.0 7.1 7.2 7.3 7.4 Votruba M, Hungerford J, Cornes PG, Mabey D, Luthert P. Primary monophasic synovial sarcoma of the conjunctiva. Br J Ophthalmol. 2002;86:1453-4.
  8. Kapoor G, Das K. Soft tissue sarcomas in children. Indian J Pediatr 2012; 79: 936-942.
  9. 9.0 9.1 Deshmukh R, Mankin HJ, Singer S. Synovial sarcoma: the importance of size and location for survival. Clin Orthop Relat Res 2004;419:155– 61.
  10. 10.0 10.1 10.2 10.3 10 Goldblum JR, Folpe AL, Weiss SW. Malignant soft tissue tumors of uncertain type: synovial sarcoma. In: Goldblum JR, Folpe AL, Weiss SW, eds. Enzinger & Weiss's soft tissue tumors. Philadelphia: Saunders Elsevier; 2014:1052-70.