Synovial Sarcoma (SS) accounts for approximately 5-10% of all soft tissue sarcomas and is the fourth most common type of sarcoma [1,2]. SS can occur anywhere in the body but it most often occurs in the para-articular areas of the lower extremities (68.7%). Monophasic epithelial synovial sarcoma is a rare tumor in younger age group with only a few cases reported.

A16 years male presented with mass in the anterior compartment of left thigh. Investigations were done. On USG well defined soft tissue mass lesion in vastus medialis region above the knee joint. On MRI, a large lobulated heterogeneously enhancing altered SI mass below the vastus medialis not involving the underlying bone. Excision biopsy was done by the department of Surgeryand sent to department of Pathology, IGMC Shimla. 

Here we received the specimen which was grossly single skin covered grey brown soft tissue mass measuring 15*12*7 cm. On cut section a well circumscribed and encapsulated greywhite grey brown to yellowish tumour with gelatinous appearance measuring 10*8*6.5cm. Few areas showed tan brown discolouration.

On microscopic examination tumour cells in sheets with plump to spindle cells having round to ovoid to elongated nuclei, evenly dispersed fine chromatin, inconspicuous nucleoli and scant to moderate amount of eosinophilic cytoplasm. Tumour cells show hemangiopericytomatous pattern. Frequent atypical mitotic figures (15/10HPF), extensive areas of necrosis, areas of mucoid/myxoid degeneration. Immunohistochemistry was done. The tumour cells were immunoreactive for Vimentin, CD99, TLE1, Bcl2. A diagnosis of Monophasic Epithelial Synovial Sarcoma was made (Figure 1-4).

Synovial sarcoma is a clinically and morphologically well-defined entity that, despite its name, is extremely uncommon in joint cavities. Furthermore, it is encountered in areas with no apparent relation to synovial structures. It occurs primarily in the paraarticular regions of the extremities, usually in close association with tendon sheaths, bursae and joint capsules. SS is primarily encountered in adolescents or young adults at 15-40 years of age. Males are affected more often than females with a male to female ratio of 1.2:1 [3]. About 17.6% of cases occur in children and young adults ages 0-19 [4].

Figure 1: Gross Image Showing a Well Encapsulated and Well Circumscribed with Gelatinous Appearance

Figure 2: Tumor Cells Showing Hemangiopericytomatous Pattern

Figure 3: Tumor Cells in Sheets (Low Power)

Figure 4: TLE1 Positivity (High Power)

Histologically, there are two major categories of synovial sarcoma, biphasic and monophasic types. Biphasic synovial sarcoma has distinct epithelial and spindle cell components in varying proportions. Of the monophasic synovial sarcomas, the vast majority are of the monophasic fibrous type, which is the most common subtype of synovial sarcoma. Although it has been suggested that monophasic epithelial-type synovial sarcomas exist, these seem to represent predominantly epithelial forms of synovial sarcoma with only subtle, small spindle cell areas [3].

Biopsy is required for definitive diagnosis. Diagnosis confirmed by molecular or cytogenetic testing for SS18-SSX fusion; commonly used methods include FISH, RT-PCR and NGS [5]. Differential diagnosis include, Metastatic carcinoma, Epithelioid sarcoma, Epithelioid MPNST, Solitary fibrous tumor and Schwannoma.

Conventional immunohistochemical markers for SS include cytokeratin, EMA, CD99 and Bcl-2. SOX-10 rather than S100 may be needed to exclude MPNST or epithelioid schwannoma in epithelial SS [6]. TLE1, a relatively newer marker, is also very helpful for diagnosis of SS. Strong and diffuse nuclear staining for TLE1 is highly suggestive of SS [7]. Although one study showed TLE1 is not entirely specific for SS [8], it is generally accepted that TLE1 is a reliable marker for SS especially in the setting of unclassifiable high-grade sarcoma [9]. Nevertheless, the result of this test should be evaluated in conjunction with proper histological and conventional immunohistochemical markers in the appropriate context. For instance, NY-ESO-1 is also an emerging diagnostic and potentially therapeutic marker for SS [10] this stain is not widely available in daily routine practice yet. Currently, the most reliable diagnostic test for SS is the chromosomal translocation t(X;18) (p11.2; q11.2), which is present in over 90% of SS cases [11,12].

Traditionally considered to be a uniformly high-grade malignancy. Advancements in therapy have lowered the incidence of recurrence and metastasis, with improved long-term survival. Prognosis is poorest in patients treated merely by local excision. With adequate surgical excision or with adjunctive radiotherapy, the recurrence rate has been significantly lower (<40%). 5-year overall survival rates for synovial sarcoma range from 56% to 76%. Major clinical factors associated with a more favourable clinical outcome include young age, tumor size smaller than 5 cm, distal extremity location and low tumor stage. Extensively calcified synovial sarcomas and tumors with poorly differentiated areas are more aggressive and metastasize in higher percentage of cases.

It is often difficult to render the diagnosis with any degree of certainties without corroborating IHC, cytogenetics or molecular studies. Monophasic epithelial SS is extremely rare and has been a controversial entity. Morphologic distinction from metastatic adenocarcinoma can be challenging and extensive sampling to reveal a cellular spindle cell tumor component is critical. Immunohistochemical staining with TLE1 or molecular studies to detect the t(X;18) translocation is a helpful tool for diagnosis of monophasic epithelial SS. Recognition and proper diagnosis of monophasic epithelial SS is of utmost importance given the different treatment modalities and better prognostic implications as compared to metastatic adenocarcinoma or other types of SS.

1. Shi W. et al. “Long-Term Treatment Outcomes for Patients with Synovial Sarcoma: A 40-Year Experience at the University of Florida.” American Journal of Clinical Oncology, vol. 36, no. 1, February 2013, pp. 83-88.

2. Herzog C.E. “Overview of Sarcomas in the Adolescent and Young Adult Population.” Journal of Pediatric Hematology/Oncology, vol. 27, no. 4, April 2005, pp. 215-218.

3. John R. et al. Enzinger and Weiss’s Soft Tissue Tumors. 6th ed., Saunders, 2014, pp. 1200-1220.

4. Ferrari A. et al. “Soft Tissue Sarcoma Across the Age Spectrum: A Population-Based Study from the Surveillance Epidemiology and End Results Database.” Pediatric Blood & Cancer, vol. 57, no. 6, December 2011, pp. 943-949.

5. Ladanyi M. et al. “Impact of SYT-SSX Fusion Type on the Clinical Behavior of Synovial Sarcoma: A Multi-Institutional Retrospective Study of 243 Patients.” Cancer Research, vol. 62, no. 1, January 2002, pp. 135-140.

6. Karamchandani J.R. et al. “Sox10 and S100 in the Diagnosis of Soft-Tissue Neoplasms.” Applied Immunohistochemistry & Molecular Morphology, vol. 20, no. 5, October 2012, pp. 445-450.

7. Terry J. et al. “TLE1 as a Diagnostic Immunohistochemical Marker for Synovial Sarcoma Emerging from Gene Expression Profiling Studies.” The American Journal of Surgical Pathology, vol. 31, no. 2, February 2007, pp. 240-246.

8. Kosemehmetoglu K. et al. “TLE1 Expression Is Not Specific for Synovial Sarcoma: A Whole Section Study of 163 Soft Tissue and Bone Neoplasms.” Modern Pathology, vol. 22, no. 7, July 2009, pp. 872-878.

9. Valente A.L. et al. “Specificity of TLE1 Expression in Unclassified High-Grade Sarcomas for the Diagnosis of Synovial Sarcoma.” Applied Immunohistochemistry & Molecular Morphology, vol. 21, no. 5, October 2013, pp. 408-413.

10. Lai J.P. et al. “NY-ESO-1 Expression in Synovial Sarcoma and Other Mesenchymal Tumors: Significance for NY-ESO-1-Based Targeted Therapy and Differential Diagnosis.” Modern Pathology, vol. 25, no. 6, June 2012, pp. 854-858.

11. Thway K. et al. “Synovial Sarcoma: Defining Features and Diagnostic Evolution.” Annals of Diagnostic Pathology, vol. 18, no. 6, December 2014, pp. 369-380.

12. Sandberg A.A. et al. “Updates on the Cytogenetics and Molecular Genetics of Bone and Soft Tissue Tumors: Synovial Sarcoma.” Cancer Genetics and Cytogenetics, vol. 133, no. 1, February 2002, pp. 1-23.