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Clinical Journal of Gastroenterology Aug 2021Worldwide, 5-10% of soft tissue sarcoma cases in adults have been attributed to synovial sarcoma. It is often reported to occur near the joints of the arm, neck, and leg...
Worldwide, 5-10% of soft tissue sarcoma cases in adults have been attributed to synovial sarcoma. It is often reported to occur near the joints of the arm, neck, and leg but rarely in the gastrointestinal tract. In this study, we report a case of synovial sarcoma arising in the stomach of a 59-year-old woman. Gastrointestinal endoscopy revealed an ulcerative and hemorrhagic tumor with marginal elevation in the fundus. Histological study showed that the tumor was composed of tightly packed spindle cells in bundles, and one of its component demonstrated significant mitotic activity (> 40/10 high-power fields) in several areas. The diagnosis was confirmed by the evidence of SS18 gene rearrangement, according to immunohistochemistry study, (including a novel SS18-SSX fusion-specific antibody), fluorescent in situ hybridization, and the identification of the SS18-SSX1 and SS18-SSX1/2/4 fusion transcripts using reverse-transcript polymerase chain reaction. No evidence of local recurrence or distant metastasis has been found in the more than 5 years since. Distinguishing synovial sarcoma in the digestive tract from other mesenchymal neoplasms, such as gastrointestinal stromal tumor, may be difficult, especially when spindle-shaped cell proliferation is predominant, as in our patient. Therefore, morphological, immunohistological, and molecular evaluations are important for a comprehensive diagnosis.
Topics: Adult; Biomarkers, Tumor; Female; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Sarcoma, Synovial; Stomach
PubMed: 33844129
DOI: 10.1007/s12328-021-01408-4 -
Histopathology Mar 2022To evaluate the diagnostic accuracy of SSX and SSX::SS18 antibodies in decalcified surgical specimens and outcome of synovial sarcomas (SS) of bone.
AIMS
To evaluate the diagnostic accuracy of SSX and SSX::SS18 antibodies in decalcified surgical specimens and outcome of synovial sarcomas (SS) of bone.
METHODS AND RESULTS
Twenty-five cases were classified as bone SS (prevalence 0.32% among malignant primary bone sarcoma). Median age was 34 years (range = 9-79). Twenty-four of 25 patients presented with non-metastatic tumours, one with lung metastases. The majority of tumours involved the long bones of extremities with metaphyseal origin. Mean size of the tumour was 7.1 cm. Twenty cases (80%) were monophasic and five (20%) were biphasic. SS18::SSX fusion-specific antibody had 92% sensitivity and 99% specificity for primary bone SS, whereas SSX C-terminus antibody had 100% sensitivity and 94% specificity. Fluorescence in-situ hybridisation (FISH) analysis was feasible in nine (36%) cases and detected SS18 rearrangement in all nine cases. All patients underwent surgical removal of their primary tumour, with adequate margins in 18 (72%) patients. Chemotherapy with metothrexate, cisplatin, doxorubicin and ifosfamide was used in the seven patients. Two patients with inadequate surgical margins received radiotherapy. With a median follow-up of 80 months (range = 6-428), 5- and 10-year overall survival (OS) was 66.6% and 47.9%, respectively, and 5 and 10 years' disease-free survival (DFS) was 36.8% [95% confidence interval (CI) = 18.0-55.7%] and 32.2% (95% CI = 14.6-51.2%), respectively. A significant improvement in 10 years' DFS in patients undergoing chemotherapy compared with patients who did not was observed (P = 0.039).
CONCLUSIONS
Our series highlights the utility of SS18::SSX fusion-specific and SSX C-terminus antibodies to support the diagnosis of SS. Adjustment chemotherapy was associated with improved prognosis in this series.
Topics: Adolescent; Adult; Aged; Antibodies; Bone Neoplasms; Child; Female; Humans; Immunohistochemistry; Male; Middle Aged; Oncogene Proteins, Fusion; Retrospective Studies; Sarcoma, Synovial; Young Adult
PubMed: 34821406
DOI: 10.1111/his.14602 -
European Journal of Radiology Dec 2020To present a pictorial essay of paediatric primary synovial sarcomas from common and less documented anatomical locations. To review the literature for the imaging... (Review)
Review
PURPOSE
To present a pictorial essay of paediatric primary synovial sarcomas from common and less documented anatomical locations. To review the literature for the imaging characteristics and prognostic factors of this rare but important childhood malignancy.
METHOD
24 primary synovial sarcoma cases (17 male, 7 female with an age range 4-21 years) were reviewed in a collaborative effort between St Jude Children's Research Hospital and Great Ormond Street Hospital for Children. Images from 19 cases were selected for inclusion, to demonstrate the spectrum of appearances across imaging modalities, in a range of different anatomical locations (upper limb, lower limb, chest/abdomen/pelvis, and head and neck). A literature review depicting the typical radiological features and the prognostic significance of these features, was also conducted.
RESULTS AND CONCLUSIONS
Primary synovial sarcoma can occur in any anatomical location, but typically within the extremities and often in close association with joints. Rarer anatomical locations described in our essay include the gastrohepatic ligament and femoral nerve sheath. We detail the salient imaging characteristics, including the T2 'triple signal' pattern which is believed to be highly specific for this particular sarcoma and in many cases predicts a poor outcome. Other poor prognostic factors include haemorrhage, lack of calcification and tumour size >10 cm. A broad range of radiological appearances are described, and in some cases related to anatomical position and size, however the presence of a soft tissue mass close to a joint in a young patient are suggestive of this diagnosis.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Sarcoma, Synovial; Soft Tissue Neoplasms; Young Adult
PubMed: 33166832
DOI: 10.1016/j.ejrad.2020.109376 -
Diagnostic Pathology Jul 2023Synovial sarcoma (SS) is a rare malignant soft tissue sarcoma that originates from primitive mesenchymal cells with epithelial differentiation potential. It is most... (Review)
Review
Synovial sarcoma (SS) is a rare malignant soft tissue sarcoma that originates from primitive mesenchymal cells with epithelial differentiation potential. It is most commonly found in the limbs and trunk. In the urinary system, it is mostly found in the kidneys. However, synovial sarcomas originating from the external urethra are extremely rare. Only one case of synovial sarcoma arising from the vulvar urethral orifice has been reported previously, and we report a second case of synovial sarcoma of the urethral orifice. In addition, a total of 16 vulvar synovial sarcomas were identified and the literature are analyzed in this report reviews from 1966 to the present.
Topics: Humans; Female; Sarcoma, Synovial; Urethra; Vulva; Sarcoma
PubMed: 37400856
DOI: 10.1186/s13000-023-01367-z -
Human Pathology Jun 2020Synovial sarcoma (SS) is a soft-tissue malignancy that most often affects patients aged between 15 and 40 years, and the prognosis for patients with metastatic disease...
Synovial sarcoma (SS) is a soft-tissue malignancy that most often affects patients aged between 15 and 40 years, and the prognosis for patients with metastatic disease is generally poor. This study was performed to evaluate checkpoint blockade immunotherapy markers in SS, including tumor mutational burden (TMB), DNA mismatch repair (MMR) status, and PDL-1 (programmed cell death ligand 1), PD1 (programmed cell death 1), and CD8 expression by normal-tumor paired whole-exome sequencing (WES) and immunohistochemistry (IHC). Outcomes evaluated included event-free and overall survival. Twenty one (21) FISH (Fluorescence In Situ Hybridization)-confirmed SS cases (11 F, 10 M) were studied, with age ranging from 8 to 89 years at diagnosis and follow-up ranging from 1 to 16 years. TMB (n = 16) ranged from 0.83 to 212/Mb (median, 1.7). Only one case showed a high TMB of 212/Mb and missense variants of MMR genes in the primary tumor, while the other 15 cases had a low TMB of less than 5/Mb. IHC was performed on all 21 tumor samples for PD-L1, PD1, CD8, and MMR proteins. PD-L1 membranous staining was detected in 3 of 21 cases (14.3%), ranging from 1 to 5% for tumor proportion score and 1-10 for combined positive score. PD1 was detected in 15 of 21 cases (71.4%), ranging from 1 to 25/HPF (high power field) (median, 2). CD8 stain was seen in all cases, ranging from 2 to 60/HPF (median, 5). PD1 staining results correlated with CD8 staining results (P < 0.0001). No correlation of TMB or IHC markers was found with survival. No fixed pattern of TMB or IHCs between primary and metastatic tumors was observed; there was no correlation between TMB or IHCs and age, location, or diagnosis subtype. All of the cases tested showed retained expression of MMR proteins. The results show that for SS, a tumor with strong driver translocation, most cases have a low TMB, but occasionally a high TMB may be present, as observed in 1 of the 16 (6.25%) cases. The demonstration of a subgroup of SS cases with high TMB might explain the 10% response rate to checkpoint immunotherapy observed in clinical trials in patients with SS.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; B7-H1 Antigen; Biomarkers, Tumor; CD8 Antigens; Child; DNA Mismatch Repair; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Phenotype; Programmed Cell Death 1 Receptor; Progression-Free Survival; Retrospective Studies; Sarcoma, Synovial; Soft Tissue Neoplasms; Time Factors; Treatment Outcome; Young Adult
PubMed: 32387103
DOI: 10.1016/j.humpath.2020.04.007 -
Expert Opinion on Therapeutic Targets 2024Soft tissue sarcomas are a group of rare, mesenchymal tumors characterized by dismal prognosis in advanced/metastatic stages. Knowledge of their molecular determinants... (Review)
Review
INTRODUCTION
Soft tissue sarcomas are a group of rare, mesenchymal tumors characterized by dismal prognosis in advanced/metastatic stages. Knowledge of their molecular determinants is still rather limited. However, in recent years, epigenetic regulation - the modification of gene expression/function without DNA sequence variation - has emerged as a key player both in sarcomagenesis and sarcoma progression.
AREAS COVERED
Herein, we describe and review the main epigenetic mechanisms involved in chromatin remodeling and their role as disease drivers in different soft tissue sarcoma histotypes, focusing on epithelioid sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors. Focusing on chromatin-remodeling complexes, we provide an in-depth on the role of BAF complex alterations in these soft tissue sarcoma histotypes. In parallel, we highlight current state-of-the-art and future perspectives in the development of rational, innovative treatments leveraging on epigenetic dysregulation in soft tissue sarcomas.
EXPERT OPINION
Therapeutic options for metastatic/advanced sarcomas are to date very limited and largely represented by cytotoxic agents, with only modest results. In the continuous attempt to find novel targets and innovative, effective drugs, epigenetic mechanisms represent an emerging and promising field of research, especially for malignant peripheral nerve sheath tumors, epithelioid and synovial sarcoma.
Topics: Humans; Sarcoma, Synovial; Epigenesis, Genetic; Neurofibrosarcoma; Sarcoma; Soft Tissue Neoplasms
PubMed: 38234142
DOI: 10.1080/14728222.2024.2306344 -
Surgery Today Nov 2014Primary pericardial synovial sarcoma is a rare disease. We herein report a case of synovial sarcoma that originated in the epicardium. A 13-year-old male visited our... (Review)
Review
Primary pericardial synovial sarcoma is a rare disease. We herein report a case of synovial sarcoma that originated in the epicardium. A 13-year-old male visited our hospital with a fever and chest pain. Copious pericardial effusion and a large intrapericardial tumor were detected. An open-chest tumor resection was performed. A solid nodular tumor was observed in the pericardial cavity. The tumor was a polypoid mass that was pedunculated and grew from the inner surface of the pericardium near the origin of the SVC and ascending aorta. Histologically, the tumor cells were uniformly spindle shaped, with an ovoid or oval nucleus, and formed solid, compact sheets and fascicles. A storiform pattern was also observed. Based on the histopathological and immunohistochemical findings, and the fluorescence in situ hybridization detection of rearrangement of the SYT gene, a monophasic synovial sarcoma was diagnosed. We discuss the diagnosis and treatment of this case and review the pertinent literature.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cardiac Surgical Procedures; Chemotherapy, Adjuvant; Doxorubicin; Gene Rearrangement; Heart Neoplasms; Humans; Ifosfamide; Male; Pericardium; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma, Synovial; Treatment Outcome
PubMed: 24022581
DOI: 10.1007/s00595-013-0720-4 -
Clinical Cancer Research : An Official... Jun 2019Synovial sarcoma is a soft tissue malignancy characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein acts as a transcriptional...
PURPOSE
Synovial sarcoma is a soft tissue malignancy characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein acts as a transcriptional dysregulator representing the major driver of the disease; however, the signaling pathways activated by SS18-SSX remain to be elucidated to define innovative therapeutic strategies.
EXPERIMENTAL DESIGN
Immunohistochemical evaluation of the Hippo signaling pathway effectors YAP/TAZ was performed in a large cohort of synovial sarcoma tissue specimens. SS18-SSX dependency and biological function of the YAP/TAZ Hippo signaling cascade were analyzed in five synovial sarcoma cell lines and a mesenchymal stem cell model . YAP/TAZ-TEAD-mediated transcriptional activity was modulated by RNAi-mediated knockdown and the small-molecule inhibitor verteporfin. The effects of verteporfin were finally tested in synovial sarcoma cell line-based avian chorioallantoic membrane and murine xenograft models as well as a patient-derived xenograft.
RESULTS
A significant subset of synovial sarcoma showed nuclear positivity for YAP/TAZ and their transcriptional targets FOXM1 and PLK1. In synovial sarcoma cells, RNAi-mediated knockdown of led to significant reduction of YAP/TAZ-TEAD transcriptional activity. Conversely, SS18-SSX overexpression in SCP-1 cells induced aberrant YAP/TAZ-dependent signals, mechanistically mediated by an IGF-II/IGF-IR signaling loop leading to dysregulation of the Hippo effectors LATS1 and MOB1. Modulation of YAP/TAZ-TEAD-mediated transcriptional activity by RNAi or verteporfin treatment resulted in significant growth inhibitory effects and .
CONCLUSIONS
Our preclinical study identifies an elementary role of SS18-SSX-driven YAP/TAZ signals, highlights the complex network of oncogenic signaling pathways in synovial sarcoma pathogenesis, and provides evidence for innovative therapeutic approaches.
Topics: Acyltransferases; Adolescent; Adult; Aged; Animals; Cell Cycle Proteins; Cell Line, Tumor; Child; Cohort Studies; Female; Humans; Male; Mice; Mice, Inbred NOD; Mice, SCID; Middle Aged; Oncogene Proteins, Fusion; Photosensitizing Agents; Sarcoma, Synovial; Signal Transduction; Transcription Factors; Verteporfin; Xenograft Model Antitumor Assays; Young Adult
PubMed: 30814111
DOI: 10.1158/1078-0432.CCR-17-3553 -
Indian Journal of Pathology &... 2021Molecular analysis is gold standard for diagnosis of synovial sarcoma (SS) but use of these ancillary techniques is limited by many practical issues like cost and...
BACKGROUND AND AIMS
Molecular analysis is gold standard for diagnosis of synovial sarcoma (SS) but use of these ancillary techniques is limited by many practical issues like cost and limited resources. Several studies analyzed TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma and few studies disagreed. The objective of the study was to evaluate immunohistochemical expression of TLE1 in synovial sarcoma and its histological mimics.
METHODS
The study included a total of 63 cases; of which 28 were synovial sarcomas (SS) and 35 its histologic mimics. A tissue microarray was constructed from these cases and subjected to TLE immunostaining. Nuclear immunoreactivity of TLE1 was graded as 0, 1+, 2+ and 3+ based on intensity and percentage of cells.
RESULTS
All SS except one (27/28; 96.4%) were positive for TLE 1. These included 18 of monophasic spindle cell type (94.7%), 5 biphasic type (100%), followed by two each (100%) of poorly differentiated and calcifying type of SS. Of the other tumours 2 GISTs (50%), 2 haemangiopericytoma (66.7%), 2 schwannomas (50%) and one mesenchymal chondrosarcoma (33.3%) were positive for TLE1.
CONCLUSION
TLE 1 is a highly sensitive marker with reasonable specificity for synovial sarcoma. Awareness of TLE1 expression in other tumours, is important to avoid misdiagnosis.
Topics: Biomarkers, Tumor; Co-Repressor Proteins; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Retrospective Studies; Sarcoma, Synovial; Sensitivity and Specificity; Soft Tissue Neoplasms; Tissue Array Analysis
PubMed: 33851625
DOI: 10.4103/IJPM.IJPM_425_20 -
Bulletin Du Cancer Feb 2016Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumor affecting children, adolescents, and young adults. Cytogenetically, more than 90% of SS is...
Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumor affecting children, adolescents, and young adults. Cytogenetically, more than 90% of SS is characterized by the t(X;18)(p11.2;q11.2), translocation resulting in two chimeric fusion genes SYT-SSX1 and SYT-SSX2, confirming histological diagnosis. Pediatric SS arises most often in soft tissues of the extremities (66% of cases), and is a localized tumor without spreading to regional lymph nodes (96% of cases) nor to metastatic sites (94% of cases). Although clinical and radiologic presentation, histologic analysis and tumor biology appear similar in pediatric and adolescent SS, outcome seems better in children than in adolescents, respectively 84% vs 60% of 5years overall survival (OS). If complete resection is the gold standard in SS, other therapeutic modalities differ between pediatric and adult populations, considering SS as an intermediate chemosensitive tumor more frequently by pediatric oncologists. Prognostic factors evaluation (tumor size, site of primary and IRS group) is necessary to establish optimal treatment strategies, with multimodal therapeutic approach in children and adolescents. Thus, recent results about the European prospective EpSSG NRSTS 05 study for children and adolescent patients with localized SS showed a 5years OS >90%. Moreover, recent somatic genetic data about SS open the debate on an appropriate strategy based and stratified on tumor genomic. Multinational prospective pediatric, adolescent and young adult study is necessary to improve optimal and appropriate approach in this rare tumor.
Topics: Adolescent; Age Factors; Child; Child, Preschool; Gene Rearrangement; Humans; Oncogene Proteins, Fusion; Prognosis; Rare Diseases; Sarcoma, Synovial; Tumor Burden
PubMed: 26774699
DOI: 10.1016/j.bulcan.2015.11.004