SYT-SSX1 enhances the invasiveness and maintains stem-like cell properties in synovial sarcoma via induction of TGF-ß1/Smad signaling.

BACKGROUND: Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is characterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. In addition, some studies have indicated that the induction of epithelial-mesenchymal transition (EMT) via the TGF-ß1/Smad signaling pathway leads to SS metastasis. METHODS: We analyzed the effects of SYT-SSX1 on the stemness of SS cells via TGF-ß1/Smad signaling in vitro. The SYT-SSX1 fusion gene high expression cell was constructed by lentiviral stable transfer technology. SYT-SSX1 and SW982 cells were cultured and tested for sphere-forming ability. The transwell migration assay and flow cytometry were used to assess the migration ability of the sphere cells as well as the expression of CSC-related markers. We treated SYT-SSX1 cells with rhTGF-ß1 (a recombinant agent of the TGF-ß1 signaling pathway) and SB431542 and observed morphological changes. A CCK-8 experiment and a western blot (WB) experiment were conducted to detect the expression of TGF-ß1 signaling pathway- and EMT-related proteins after treatment. The SYT-SSX1 cells were then cultured and their ability to form spheres was tested. Flow cytometry, WB, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CSC surface markers on SYT-SSX1 sphere cells. RESULTS: It was found that SYT-SSX1 has stronger sphere-forming ability, migration ability, and higher expression of CSC-related molecules than SW982 cells. Through treating SYT-SSX1 and SW982 cells with rhTGF-ß1 and SB431542, we found that TGF-ß1 enhanced the proliferation of cells, induced EMT, and that TGF-ß1 enhanced the characteristics of tumor stem cells. CONCLUSIONS: Our results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGF-ß1/Smad signaling. These findings reveal an effective way to potentially improve the prognosis of patients with SS by eliminating the characteristics of cancer stem cells (CSCs) during treatment.

Primary Renal Synovial Sarcoma Case Series: Clinical Profile and Management of a Rare Entity.

Synovial sarcomas occur predominantly in the extremities. Primary renal synovial sarcoma is a rare entity. Very few cases have been reported in the literature. Clinical and radiological features are similar to renal cell carcinoma with the diagnosis being established after surgery based on histopathology, immunohistochemistry, and chromosome studies. There are no established guidelines on the role of adjuvant treatment in the management of this disease. We herein present a series of 3 cases managed at 2 institutions. In the current series, all patients had venous thrombus, and surgery was the mainstay of treatment. One patient received neoadjuvant chemotherapy after a preoperative biopsy which was done as she did not respond to chemotherapy for a presumptive diagnosis of Wilm's tumor.

Intraosseous synovial sarcoma of the distal ulna: a case report and review of the literature.

BACKGROUND: Synovial sarcoma is a relatively rare type of soft tissue sarcoma. The commonly observed symptom is a deep-seated palpable mass accompanied by pain or tenderness. Thus, it is considered a soft tissue sarcoma and rarely occurs primarily in bone. However, only few studies have been reported on intraosseous synovial sarcoma, and reports on cases with cytogenetic or molecular confirmation are even rarer. We report a case of intraosseous synovial sarcoma of the distal ulna that has been confirmed using histopathological examination and molecular analysis. CASE PRESENTATION: A 77-year-old female was referred to our hospital with a 1-month history of right wrist pain after housework. Clinical and imaging findings suggested a benign bone tumor that was enhanced by Gd-DTPA. It was thought that the tumor was possibly an enchondroma. Initially, we planned to evaluate the benignancy of the tumor with intraoperative frozen section, followed by curettage and bone graft at one stage However, when considering carefully, characteristics of the tumor did not perfectly match those of any diagnostic categories including enchondroma. Therefore, an incisional biopsy was performed and revealed that the tumor was synovial sarcoma. Following an elaborate plan, the patient underwent a wide resection of the tumor at the distal part of the right ulna. Reverse transcription-polymerase chain reaction (RT-PCR) from the resected specimen and sequencing of RT-PCR products demonstrated a chimeric SYT-SSX1 transcript, confirming the diagnosis of synovial sarcoma. CONCLUSIONS: Synovial sarcoma is seldom considered in differential diagnosis of bone tumors because it is difficult to line up such an unusual diagnosis as a differential diagnosis. When the lesion does not perfectly fit into any diagnostic category, when the initial image diagnosis appears unconvincing, biopsy and pathology are indicated, recalling Jaffe's triangle. According to these diagnostic processes, the patient successfully completed the treatment for this rare intraosseous synovial sarcoma, following a careful plan based on the preoperative diagnosis.

Primary synovial sarcoma of the kidney: a case report of complete pathological response at a Lebanese tertiary care center.

BACKGROUND: Primary synovial sarcoma of the kidney is a rare type of soft tissue sarcoma. Its presenting features can resemble those of other renal tumors; rendering its early diagnosis, a dilemma. Several cases of renal synovial sarcoma have been reported in the literature with varying treatment options and outcomes. This article describes a rare case of primary renal synovial sarcoma and reviews all cases in the literature. CASE PRESENTATION: A 26-year-old male presented with flank pain and hematuria. Initially diagnosed with Wilm's tumor, revision of pathology and histology, along with the immunohistochemical profile, confirmed, nevertheless, the diagnosis of primary monophasic synovial sarcoma of the kidney with the SYT-SSX2 fusion transcript. Follow-up, post nephrectomy, revealed recurrence within the lungs and at the surgical bed. Surgical resection followed by adjuvant chemotherapy regimen constituting of Doxorubicin and Ifosfamide, achieved complete pathological response. CONCLUSION: In this case report, we emphasize the need for accurate diagnosis and prompt treatment. We propose multimodality treatment approach including surgery along with anthracycline-based chemotherapy to induce complete remission.

The prognostic impact of SYT-SSX fusion type and histological grade in pediatric patients with synovial sarcoma treated according to the CWS (Cooperative Weichteilsarkom Studie) trials.

BACKGROUND: The aim of our analysis was the evaluation of the prognostic impact of SYT-SSX fusion status and histological grading in synovial sarcoma (SS) of children and adolescents in the context of the consistent multimodal treatment strategy of the CWS (Cooperative Weichteilsarkom Studie; Cooperative Soft Tissue Sarcoma Study Group) and in comparison with other risk factors. PROCEDURE: Between 1986 and 2006, out of 243 patients with SS, tumor samples from 84 patients with localized disease were available for RT-PCR analysis. Outcome depending on fusion status in the context with known clinical risk factors was analyzed. RESULTS: No prognostic significance was shown for SYT-SSX fusion status and for histological grade. Highest significance of negative prognostic impact was found for large tumor size in uni- and multivariate analysis (P < 0.01). Furthermore, male gender was shown to be an adverse prognostic factor in multivariate analysis (P = 0.01). CONCLUSIONS: Based on our results, neither histological grading nor SYT-SSX fusion status seems to be suitable for outcome prediction and risk stratification in localized SS treated according to the CWS. This is in contrast to several other publications concerning more heterogeneous age groups including children and adults, and this indicates that prognostic factors should not be interpreted apart from the particular study population and the therapeutic context.

[Primary renal synovial sarcoma]. / Synovialosarcome rénal primitif.

The primary renal synovial sarcoma is a rare tumor with a poor prognosis. It may be confused with other types of mesenchymal kidney tumors because of similarities in clinical and histological appearance. About 60 cases have been described in the literature. We report a case of a 66-year-old man presenting a primary synovial sarcoma of the right kidney with a vascular invasion of the inferior vena cava and right renal vein. The diagnosis was confirmed in molecular biology by reverse transcription polymerase chain reaction (RT-PCR) which demonstrated a unique chromosomal translocation t(X;18) with SYT-SSX2 fusion transcripts. We describe here the case with a brief review.

Identification of CT Features to Differentiate Pulmonary Sarcoma from Carcinoma.

Background Primary lung sarcoma (PLS) differs in management protocols and prognosis from the more common primary lung carcinoma (PLC). It becomes imperative to raise a high index of suspicion on radiological and pathological features. Purpose The aim of this study is to highlight the variable imaging appearances of PLS compared with PLC, which impacts radiologic - pathologic correlation. Materials and Methods A retrospective observational study of 68 patients with biopsy-proven lung tumors who underwent baseline imaging at our tertiary care cancer hospital was conducted between January 2018 and March 2022. The patient details and imaging parameters of the mass on contrast-enhanced computed tomography (CECT) were recorded and analyzed for patients with PLS and compared with PLC. Follow-up imaging was available in 9/12 PLS and 52/56 PLC patients. Results Among 12 patients with PLS, 5 patients had synovial sarcoma on histopathology. PLS was seen in patients with a mean age of 40.8 years; the mass showed a mean size of 13.2 cm, lower lobe (75%), parahilar (75%), hilar involvement (41.7%), oval shape (41.7%), circumscribed (25%) or lobulated (75%) margins, lower mean postcontrast attenuation of 57.3 HU, fissural extension (50%), calcification (50%), and no organ metastasis other than to the lung. PLC (56 patients) was seen in the elderly with a mean age of 54.8 years; the mass showed a mean size of 5.7 cm, irregular shape (83.9%), spiculated margins (73.2%), higher mean postcontrast attenuation (77.3 HU), chest wall infiltration (30.4%), and distant metastasis (58.9%) at baseline imaging. A statistically significant difference ( p < 0.05) was seen between sarcoma and carcinoma in the mean age, size, site, shape, margins, postcontrast attenuation, presence of calcifications, fissural extension, and distant metastasis. Conclusion The distinct imaging features of sarcoma help in differentiating it from carcinoma. This can also be used to corroborate with histopathology to achieve concordance and guide clinicians on further approach.

Biphasic synovial sarcoma with epithelial predominance reminiscent of adenocarcinoma: a diagnostic challenge.

Synovial sarcoma (SS) is a rare tumour of unknown origin with peak incidence between 10 and 35 years. Although it arises in juxta-articular location, SS is a misnomer and has no true relationship with synovium. In this case report, we present an elderly female patient with a long-standing history of thigh mass which was initially misdiagnosed as metastatic adenocarcinoma deposits on fine needle aspiration cytology, and again misdiagnosed as malignant adnexal skin tumour on core needle biopsy and referred for further management. Here, we discuss the challenges faced in the diagnosis of SS on a small biopsy and ways to differentiate it from other morphological mimickers. Therefore, we aim to increase the awareness of soft tissue tumours that microscopically appear like adenocarcinoma, which is a potential diagnostic pitfall. We also highlight the importance of morphological diagnosis and the utility of molecular testing using fluorescence in situ hybridisation, to arrive at the correct diagnosis of SS.

Tonsillar synovial sarcoma, unusual anatomical location: case report and literature review.

BACKGROUND: Synovial sarcoma is a rare soft tissue malignancy, occasionally found in the head and neck region. The diagnosis necessitates a multidisciplinary approach involving the clinical presentation, proper imaging studies and histological confirmation, with molecular testing for definitive identification. Treatment entails surgical resection with adjuvant therapies as needed. CASE PRESENTATION: A 33-year-old male patient presented with globus sensation concomitant with right-sided neck swelling. He was clinically found to have right tonsil enlargement with posterior extension. Therefore, he underwent right tonsillectomy with pharyngoplasty. Histopathological examination revealed a biphasic tumor consistent with synovial sarcoma, confirmed by immunohistochemistry and fluorescence in situ hybridization. CONCLUSIONS: Tonsillar synovial sarcoma represents a diagnostic challenge, requiring a high index of suspicion and comprehensive evaluation. With only twenty previously published cases documented in the literature, awareness of this rare presentation is crucial for prompt diagnosis and appropriate management. Collaboration among multidisciplinary healthcare teams and ongoing research efforts are essential for optimizing diagnostic accuracy, treatment efficacy, and patient outcomes in this rare malignancy.

An Extremely Rare and Demanding Diagnosis of Primary Renal Synovial Sarcoma: A Case Report.

Primary renal synovial sarcoma (PRSS) is an extremely rare malignancy. The diagnosis of PRSS is unforeseen due to the absence of clinical and radiological typical aspects. Here, we present a case of a 69-year-old male with complaints of hematuria and left lumbar pain. Abdominal-pelvic computed tomography scan with contrast injection showed a solid mass of 8cm diameter in the left kidney and renal vein tumor thrombus. The patient was further subjected to robotic-assisted left radical nephrectomy and renal vein thrombectomy. We concomitantly performed left adrenalectomy and paraaortic lymphadenectomy. Immunohistochemical and genetic analysis revealed PRSS. This entity is characterized by abnormal chromosomal translocation t(X;18)(p11.2; q11.2) and consequently the characteristic SYT-SSX fusion gene. Due to the disease's rarity and severity, diagnosis and management of PRSS rely upon a demanding and multidisciplinary approach.

Case Report: Primary Intraosseous Poorly Differentiated Synovial Sarcoma of the Femur.

Primary intraosseous poorly differentiated synovial sarcoma is exceedingly rare. Here, we present a case of primary intraosseous poorly differentiated synovial sarcoma from the proximal femur in a 16-year-old girl. The case was initially misdiagnosed, but the correct diagnosis of synovial sarcoma was eventually confirmed by fluorescence in situ hybridization and next-generation sequencing. We review the literature pertaining to synovial sarcoma and show that this case is the second molecularly proven intraosseous poorly differentiated synovial sarcoma in the literature. Recognition of intraosseous synovial sarcoma composed of small round cells is imperative in order to avoid misdiagnosis of the tumor as Ewing sarcoma and other small round-cell tumors, all of which have markedly different clinical management.

Primary intracranial synovial sarcoma: A case report and review of literature.

Background: Primary intracranial synovial sarcomas (PrISS) are unusual dural based mesenchymal tumors seen most commonly in the supratentorial compartment. They can mimic a spontaneous intracranial hemorrhage or a high-grade glioma on imaging. Case Description: A 31-year-old male presented with headache and right hemiparesis for 2 weeks. CT brain revealed a left frontal spontaneous intracerebral hemorrhage. PrISS revealed a heterogeneously ring enhancing solid cystic lesion with attachment to convexity dura. Intraoperatively, it mimicked a high-grade glioma. Histopathology report showed features of a synovial sarcoma, which was later confirmed with IHC. Classical SYT-SSX2 translocation was confirmed only on RTPCR after fluorescent in situ hybridization (FISH) was negative for same. Whole body positron emission tomography (PET-CT) did not show any extracranial tumor. Despite radiotherapy, there were recurrence and tumor progression at 6 months and the patient succumbed 11 months later. Conclusion: PrISS is an unusual aggressive intracranial neoplasm that carries a worse prognosis when compared nonintracranial synovial sarcomas. Molecular cytogenetics (FISH and RTPCR) are essential for confirming the diagnosis, though FISH seems to have a lower sensitivity and can yield false negative results as was noted in this case.

The role of SYT-SSX fusion gene in tumorigenesis of synovial sarcoma.

Synovial sarcoma (SS) is an aggressive malignancy of an unknown tissue origin that is characterized by biphasic differentiation. A possible basis of the pathogenesis of SS is pathognomonic t(X;18) (p11.2; q11.2) translocation, leading to the formation and expression of the SYT-SSX fusion gene. More than a quarter of the patients die of SS metastasis within 5 years after the diagnosis, but the pathogenic factors are unknown. Therefore, there is an urgent need to explore the pathogenesis, invasion, metastasis, and clinical treatment options for SS, especially molecular-targeted drug therapy. Recent studies have shown that the SYT-SSX fusion gene associated with SS may be regulated by different signaling pathways, microRNAs, and other molecules, which may produce stem cell characteristics or promote epithelial-mesenchymal transition, resulting in SS invasion and metastasis. This review article aims to show the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the SYT-SSX fusion gene function. Therefore, this review may provide a more innovative and broader perspective of the current research, treatment options, and prognosis assessment of SS.

Primary rectal monophasic synovial sarcoma.

Synovial sarcoma is a rare malignant mesenchymal neoplasm that often occurs in the extremities. Less than 70 cases of primary synovial sarcoma occurring in the digestive system have been reported. We present a case of a 48-year-old woman with a spindle cell tumor in the rectum that stained positive for AE1/3 (focal), vimentin, CD99, BCL2, EMA (focal), and MiB-1 (15%). Ultimately, the lesion was diagnosed as a primary rectal monophasic synovial sarcoma and confirmed by molecular testing for SYT/SSX1 gene fusion. Analysis of previous publications indicated that patients of advanced age or a large tumor size (≥5 cm) have a higher risk of progressing rapidly to death after diagnosis of synovial sarcoma in the digestive system.

Primary Synovial Sarcoma of the Thyroid: Challenges in Cytologic Diagnosis and Review of the Literature.

BACKGROUND: Primary synovial sarcoma (SS) of the thyroid (PSST) is extremely rare. Its differential diagnosis from other neoplasms is essential since it has different management protocols and prognosis. CASE: A 26-year-old man with a 4.5-cm solid lobulated mass was seen at an outside hospital. Fine needle aspiration (FNA) was interpreted as a papillary carcinoma, and a total thyroidectomy was performed. The final histologic diagnosis was spindle epithelial tumor with thymus-like differentiation (SETTLE). No metastases were detected at that time, and the patient received radioactive iodine treatment. Two years post-surgery, he was seen at our hospital with a local recurrence, and FNA was considered as consistent with SETTLE. The mass was resected, and a left modified radical neck dissection was performed. The tumor revealed necrosis and a high mitotic index. Following histologic, immunohistochemical, and molecular studies, the tumor was classified as a PSST. The patient received chemotherapy and targeted immunotherapy, but he died 41 months after the initial presentation. CONCLUSION: The main diagnostic pitfall of PSST is SETTLE. The presence of mitotic figures and basal lamina material, negative staining for smooth muscle actin, and positive staining for transducer-like enhancer of split 1 antibody favor SS over SETTLE. SYT gene rearrangement is essential to establish the definitive diagnosis of PSST.

Exploring Two Protocols of FISH Using Cytocell SYT-SSX Probe on Formalin Fixed Paraffin Embedded Tissue Sections.

BACKGROUND: Chromosomal translocation t(X;18)(p11.2;q11.2) is the cytogenetic hallmark of synovial sarcoma and have been identified as an alternative diagnostic strategy in differentiating synovial sarcoma from other histologic mimics. This study was carried out to test the efficacy of two FISH protocols using the SYT-SSX break apart probe from Cytocell. METHODOLOGY: Representative paraffin blocks of synovial sarcoma were utilized in this study. FISH study was performed on formalin-fixed paraffin embedded tissue sections using the SYT-SSX break apart probe from Cytocell, to detect two form of SYT-SSX transcript, SYT-SSX1 and SYT-SSX2. FISH protocol, including the hybridization was done following two different protocols, Cytocell FISH protocol and Optimized Dako FISH protocol. RESULTS: Tissue samples subjected to FISH using Cytocell FISH protocol showed the absence of signal corresponding to the probe used. Utilizing Optimized Dako FISH protocol, the two signals (red and green) corresponding to the break-apart probes was detected. These findings suggested that Optimised Dako FISH protocol is more suited for use with the tested probe on paraffin embedded tissues in comparison to Cytocell FISH protocol. CONCLUSION: Optimised Dako FISH protocol was noted to be more suited for detecting SYT-SSX FISH signals on paraffin embedded tissues in comparison to Cytocell FISH protocol.

Primary renal synovial sarcoma: two cases and review of the literature.

OBJECTIVE: To investigate the clinicopathological features, treatment, and prognosis of primary renal synovial sarcoma. METHOD: Retrospectively collected and analyzed clinical and pathological data of two cases of patients with renal primary synovial sarcoma, and reviewed domestic and foreign related literature. RESULTS: The first patient was admitted for progressive enlargement of a left renal mass, then she underwent a radical resection of left kidney and adrenal gland, and the final diagnosis was primary renal synovial sarcoma. However, the tumor progressed with multiple nodules in the left peritoneal retroperitoneal space and abdominal wall 3 months later. The second patient was hospitalized for a left lung mass and left renal mass after 3 months. She received left nephrectomy and left lower lobectomy. The final diagnosis was primary renal synovial sarcoma with extensive metastasis in both lungs and pelvic and abdominal cavity. The patient underwent chemotherapy and targeted therapy after operation, and died because of tumor burden after 23 months. CONCLUSION: Primary renal synovial sarcoma is a rare soft tissue tumor in the kidney with a poor prognosis. An accurate diagnosis needs consideration of the morphology, immunohistochemistry, and SYT-SSX gene results. Clinically, radical nephrectomy is the main strategy, and adjuvant ifosfamide-based chemotherapy after operation has benefits.

In silico and in vitro screening of small molecule Inhibitors against SYT-SSX1 fusion protein in synovial sarcoma.

Synovial sarcoma (SS) is characterized by a tumour specific chromosomal translocation t(X;18) (p11;q11) which results in the formation of SYT-SSX1 fusion protein. This fusion protein represents a clear therapeutic target and molecules specifically targeting SYT-SSX1 fusion protein are currently not available. In this study, SYT-SSX1 fusion protein sequence was retrieved from Uniprot and 3D structure was generated using I-TASSER modeling program. A structure based computational screening approach has been employed using Glide docking software to identify potential SYT-SSX1 small molecule inhibitors that bind to the junction region of the fusion protein. The obtained inhibitors were further filtered based on the docking score and ADME/T properties. Ten best fit compounds were chosen for in vitro studies. The anti-proliferative activities of these 10 compounds were screened in Yamato, ASKA (carries SYT-SSX1 fusion protein) and other sarcoma cell lines such as A673, 143B to understand the specificity of inhibition of the chosen compounds. The in vitro activity was compared against HEK293 cell lines. The compound 5-fluoro-3-(1-phenyl-1H-tetraazol-5-yl)-1H-indole (FPTI) was found to be selectively cytotoxic in synovial sarcoma cell lines (Yamato and ASKA) and this compound also showed insignificant anti proliferative activity on other cell lines. Further, target gene expression study confirmed that FPTI treatment down-regulated SYT-SSX1 and modulated its downstream target genes. Cell cycle analysis revealed the involvement of an apoptotic mechanism of cell death. Further experimental validations may elucidate the therapeutic potentials of FPTI against SYT-SSX1 fusion protein.

Cytologic features of primary monophasic synovial sarcoma of the thyroid gland.

Synovial sarcoma (SS) is a rare soft tissue tumor, commonly arising in para-articular areas of extremities, but can also present in the head and neck area. However, primary SS of the thyroid gland is an extremely rare tumor which has been reported only five times in previous English literatures. This report presents fine needle aspiration (FNA) cytology of primary monophasic SS of the thyroid gland. A 47-year- old woman incidentally detected thyroid nodule in the isthmus of right thyroid gland on an ultrasonography by regular health check-up. Because the possibility of malignancy could not be ruled out, FNA and surgical resection were performed. The cytological, histopathological, immunohistochemical, and molecular genetic study of SYT-SSX transcript were discussed. For the past 3 years of follow-up after surgery, no recurrence or metastasis has been identified.

Primary orbital synovial sarcoma: A clinicopathologic review with a differential diagnosis and discussion of molecular genetics.

Synovial sarcoma is a soft-tissue sarcoma of the extremities developing in young adults that has rarely been reported in the orbit. Synovial sarcoma is associated with a unique translocation, resulting in an SYT-SSX fusion gene. We analyze 7 published periocular cases, together with the current one, to gain a better appreciation of the features of the tumor in this location and to compare the findings with those derived from nonophthalmic studies. An inferior orbital mass developed in a 31-year-old woman after experiencing periorbital and hemifacial pain for more than a decade. Radiographically, the mass was circumscribed and displayed coarse internal calcifications. A large but subtotal excision with histopathologic examination disclosed a primitive tumor composed of spindled and ovoid cells. Immunohistochemistry demonstrated positivity for nuclear transducin-like enhancer of split 1 and membranous CD99, typical for synovial sarcoma. Fluorescence in situ hybridization identified a (X,18) translocation in the tumor cells. The patient underwent postoperative adjuvant proton beam radiotherapy with a good response that has been maintained during 1 year of follow-up. Orbital soft-tissue tumors of all types are increasingly identified by their distinctive genetic signatures that offer more specificity than standard immunohistochemical tests.