Mediastinal monophasic synovial sarcoma with vertebral metastases: A case report.

Mediastinal monophasic synovial sarcoma is a rare subtype that often lacks specific imaging characteristics, posing diagnostic challenges. This case report describes a mediastinal monophasic synovial sarcoma with vertebral metastasis, emphasizing imaging findings, differential diagnosis, and pathological features, thereby providing crucial support for accurate diagnosis and treatment planning.

Establishment and characterization of NCC-SS6-C1: a novel patient-derived cell line of synovial sarcoma.

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5-10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.

Primary cardiac synovial sarcoma originating from the atrial septum and associated pulmonary infarction: a case report.

BACKGROUND: Primary cardiac synovial sarcoma is a rare condition with limited treatment options for advanced stages. Surgery and chemotherapy are currently the mainstay treatments; however, survival rates remain low. CASE PRESENTATION: A 64-year-old woman presenting with symptoms of chest tightness and shortness of breath was found to have an obstructive right atrial mass, along with pulmonary infarction and metastasis. She was ultimately diagnosed with advanced primary cardiac synovial sarcoma. Following surgery, the patient's symptoms improved, and she underwent chemotherapy and anti-angiogenic therapy, but unfortunately, her survival time was only 8 months. CONCLUSION:  This case report aims to enhance clinicians' understanding of the diagnosis and treatment of primary cardiac synovial sarcoma. Enhancing both survival outcomes and quality of life in individuals with primary cardiac synovial sarcoma continues to present a significant challenge.

Whether unplanned excision on synovial sarcoma will influence the prognosis? An retrospective analysis of prognostic factors in 54 synovial sarcoma cases at a single center.

OBJECTIVE: In this study, we examined the reason and prognosis of unplanned excision on synovial sarcoma. METHODS: We retrospectively analyzed 54 patients diagnosed with synovial sarcoma between March 2013 and February 2021, including 26 cases of unplanned excision surgery. Patients were divided into two groups based on whether they underwent unplanned excision. Then, factors such as gender, age, tumor size, tumor location, American Joint Committee on Cancer (AJCC) staging, unplanned excision, time of onset, duration of disease, radiotherapy, chemotherapy, amputation, local recurrence factors, and death were statistically evaluated. RESULTS: The results of a multivariate analysis revealed that the AJCC staging is an independent factor for patient prognosis. When patients were divided into two groups, those who had undergone unplanned excision and those who had not, statistical analysis revealed that there was no difference of survival between two groups, but tumor size and AJCC staging had statistical difference. To further explore the influences of unplanned excision, we performed propensity score analysis with 1:1 matching using the nearest neighbor matching method to balance the covariates between the two groups. There was no difference of survival between two groups after propensity score matching. CONCLUSION: Unplanned excision is commonly performed in synovial sarcoma and do not impact the prognosis after extensive resection.

Rare mediastinal small round cell melanoma with synovial sarcoma-like immunophenotype: A potential diagnostic pitfall.

Melanoma can pose a significant diagnostic challenge due to the high variability in histological morphology and expression of non-melanocytic immunomarkers. We present a case of a 47-year-old male with an aggressive mediastinal neoplasm and disseminated disease posing several diagnostic challenges. Multiple biopsies were submitted from different anatomic locations and during multiple time points showing an undifferentiated round cell tumor (URCT) with synovial sarcoma-like immunophenotype. SS18::SSX fusion was sought through NGS study for diagnostic confirmation. NGS results revealed NRAS and CDKN2A mutations and absence of fusions, resulting in a new review of the histologic material with a broader immunohistochemical panel, finding strong positivity to melanic antibodies. This case is an illustrative example of a malignant melanoma with small round cell morphology showing aberrant expression of CD99, BCL2, TLE1 and SS18-SSX antibodies exposing a potentially hazardous pitfall highlighting the importance of a wide differential diagnosis and the role of confirmational studies with molecular tests.

Epidemiology, incidence, and survival of synovial sarcoma of children: a SEER database analysis.

Background: Roughly 5% to 10% of soft tissue sarcomas fall under the category of synovial sarcomas (SSs), a rare and malignant tumor originating from soft tissues with unclear differentiation, primarily affecting teenagers and young adults. The goal of this study was to assess the latest survival rates for SS of children and the risk factors affecting survival using the Surveillance, Epidemiology and End Results (SEER) database. Methods: Age, sex, race, SEER stage, surgery, radiation, chemotherapy, laterality, site of SS, and survival time were collected in the SEER database for survival and prognostic factor analysis. The overall survival curves and cancer special survival were obtained by Kaplan-Meier according to different factors. A multivariate Cox regression model and a predictive nomogram have also been constructed. Results: A total of 130 patients were enrolled in the study. In the overall survival analysis, age (P=0.01), male (P=0.04), no surgery (P<0.01), chemotherapy (P<0.01), primary tumor site in soft tissue (P=0.02), and in distant of SEER stage (P<0.01) were associated with a worse prognosis in children with SS. Multivariate analysis showed that chemotherapy and in distant of SEER stage were independent indicators of unfavorable prognosis. A similar result was released in the specialized cancer survival analysis. A nomogram was used to predict the prognosis of SS in children and a calibration curve was used to validate the nomogram prediction against the actual observed survival outcomes. Conclusions: In summary, chemotherapy, and worse SEER stage were associated with poorer overall and cancer special survivals. Nomogram was able to predict the probability of 1-, 5- and 10-year overall survivals and showed good consistency with the actual observed outcomes.

Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.

BACKGROUND: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed. PATIENTS AND METHODS: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes. RESULTS: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting. CONCLUSIONS: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes.

Spindle epithelial tumor with thymus-like elements (SETTLE): a diagnostic challenge with distinct therapeutic implication; case report.

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.

Contemporary surgical management of pediatric non-rhabdomyosarcoma soft tissue sarcoma.

Non-rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5 cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high-risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.

Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma.

Background: Synovial sarcoma (SS) is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics, associated with a poor prognosis due to frequent metastasis to a distant organ, such as the lung. Histone deacetylase (HDAC) inhibitors (HDACis) are arising as potent molecular targeted drugs, as HDACi treatment disrupts the SS oncoprotein complex, which includes HDACs, in addition to general HDACi effects. To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells, we examined cellular responses to HDACi treatment in combination with two-dimensional (2D) and 3D culture conditions. Methods: Using several SS cell lines, biochemical and cell biological assays were performed with romidepsin, an HDAC1/2 selective inhibitor. SN38 was concomitantly used as an ameliorant drug with romidepsin treatment. Cytostasis, apoptosis induction, and MHC class I polypeptide-related sequence A/B (MICA/B) induction were monitored to evaluate the drug efficacy. In addition to the conventional 2D culture condition, spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance. Results: By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells, we observed that responsiveness is diverse in each cell line. In the apoptotic inducible cells, co-treatment with SN38 enhanced cell death. In nonapoptotic inducible cells, cytostasis and MICA/B induction were observed, and SN38 improved MICA/B induction further. As a novel efficacy of SN38, we revealed TWIST1 suppression in SS cells. In the spheroid (3D) condition, romidepsin efficacy was severely restricted in TWIST1-positive cells. We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form, and concomitant SN38 treatment along with romidepsin reproduced the reaction. Conclusions: The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression.

Unveiling Rarity: A Case Report of a Poorly Differentiated Synovial Sarcoma Mimicking a Plunging Ranula.

Synovial sarcomas are uncommon and highly aggressive sarcomas. Typically, they start in the soft tissues of the extremities, although they may develop in the head and neck region in rare cases. When they do, they usually present with localized symptoms in the affected area. Our patient is a 20-year-old man without a medical history who complained of a three-month history of submental swelling of the left side with a non-tender, palpable 5 cm mass. Initially believed to be a plunging ranula, the patient underwent transoral excision of the left submandibular soft tissue mass in the neck by the ear, nose, and throat (ENT) specialist. The pathological analysis of the mass confirmed the presence of a poorly differentiated synovial sarcoma. A postoperative neck imaging was performed, which showed a significant decrease in mass size compared to the previous imaging; however, the mass was still present. This is one of the few described cases of a poorly differentiated synovial sarcoma located on the floor of the mouth. Therefore, it highlights the importance of considering it as a possible differential diagnosis of head and neck pathologies.

68Ga-DOATATOC Brain PET/CT Imaging in a case of Dural Metastasis from Synovial Sarcoma.

We present the case of a 70-year-old male patient who underwent a gallium-68 (68Ga)-DOTATOC brain positron emission tomography (PET)/computed tomography (CT) for the assessment of a tumorous lesion on the dura. The patient had previously undergone below-knee amputation due to a mass of synovial sarcoma on the left foot and completed adjuvant chemotherapy approximately 3 months ago. Subsequently, a well-demarcated papillary solid mass located on the dura was surgically excised. Pathological examination confirmed that the dural metastasis originated from synovial sarcoma and post-operative magnetic resonance imaging (MRI) revealed no residual tumor. We conducted a 68Ga-DOTATOC brain PET/CT suspecting a meningioma given the presence of a dural mass. The result showed lower uptake (maximum standardized uptake [SUVmax 4.9]) than the pituitary gland (SUVmax 9.3). Thus, we successfully conducted a differential diagnosis of metastasis from the preexisting malignancy rather than the meningioma. 68Ga-DOTATOC PET/CT is a valuable tool for the differential diagnosis of meningioma. However, metastasis should also be considered, especially in patients with a history of malignancy and lesions showing mild 68Ga-DOTATOC uptake.

Combination of HDAC and FYN inhibitors in synovial sarcoma treatment.

The SS18-SSX fusion protein is an oncogenic driver in synovial sarcoma. At the molecular level, SS18-SSX functions as both an activator and a repressor to coordinate transcription of different genes responsible for tumorigenesis. Here, we identify the proto-oncogene FYN as a new SS18-SSX target gene and examine its relation to synovial sarcoma therapy. FYN is a tyrosine kinase that promotes cancer growth, metastasis and therapeutic resistance, but SS18-SSX appears to negatively regulate FYN expression in synovial sarcoma cells. Using both genetic and histone deacetylase inhibitor (HDACi)-based pharmacologic approaches, we show that suppression of SS18-SSX leads to FYN reactivation. In support of this notion, we find that blockade of FYN activity synergistically enhances HDACi action to reduce synovial sarcoma cell proliferation and migration. Our results support a role for FYN in attenuation of anti-cancer activity upon inhibition of SS18-SSX function and demonstrate the feasibility of targeting FYN to improve the effectiveness of HDACi treatment against synovial sarcoma.

A rare case of a young man with mediastinal synovial sarcoma.

Synovial sarcoma is a rare and aggressive tumor that primarily affects soft tissues, including the mediastinum, and predominantly affects younger adults. A 23-year-old male patient with mediastinal synovial sarcoma underwent debulking surgery and received 3 cycles of doxorubicin, ifosfamide, and mesna chemotherapy. Mediastinal synovial sarcoma presents diagnostic challenges and poor prognosis. Treatment involves surgical resection, adjuvant chemotherapy, and radiotherapy. Mediastinal synovial sarcoma can be diagnosed through histopathological and immunohistochemical examination. Adjuvant chemotherapy led to a partial response, showing a decrease in tumor size and resolution of pleural effusion, demonstrating a positive interim outcome.

Synovial Sarcoma of the Kidney: Diagnostic Pitfalls in a Case with Myxoid Monophasic Differentiation and No Epithelial Biomarkers Expression.

Synovial sarcomas are soft tissue tumours of uncertain origin, most commonly found in the upper or lower extremities. They are characterised by distinctive chromosomal rearrangements involving the gene SS18. Synovial sarcomas can occasionally arise also in visceral sites, but retroperitoneal SSs are very unusual. Among them, a few primary renal synovial sarcomas have been described in the scientific literature. Primary renal synovial sarcomas tend to be monophasic and often show cystic changes. Histologically, they can closely resemble other primary kidney tumours, mainly paediatric tumours such as nephroblastoma and clear cell sarcoma of the kidney. In the current work, a primary synovial sarcoma of the kidney with unusual morphological features (extensively myxoid stroma and immunohistochemical positivity for BCOR) is described. Molecular analysis, through targeted RNA sequencing, was of invaluable help in reaching the correct diagnosis. Despite locally advanced disease at presentation, the patient showed an unexpectedly brilliant response to chemotherapy.

Novel candidate metastasis-associated genes for synovial sarcoma.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM-receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co-expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non-metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.

Potentially actionable targets in synovial sarcoma: A tissue microarray study.

BACKGROUND: Synovial sarcoma (SynSa) is one of the most common translocation-related soft tissue sarcomas. Patients with metastatic SynSa have limited treatment options and a very poor prognosis. Several novel experimental therapies are currently being explored in clinical trials, including T cell-based therapies targeting cancer testis antigens such as New York esophageal squamous cell carcinoma 1 (NY-ESO-1) or melanoma-associated antigen A4 (MAGE-A4), and degraders targeting bromodomain-containing protein 9 (BRD9). Preclinical studies investigate inhibitors of Yes associated protein 1 (YAP1), transcriptional co-activator with PDZ-binding motif (TAZ) and inhibitors of chemokine receptor 4 (CXCR4). METHODS: We explored the immunohistochemical expression of these targets using a tissue microarray (TMA) constructed from 91 clinical SynSa samples and correlated these findings with corresponding clinicopathological data. RESULTS: Expression of MAGE-A4 and NY-ESO-1 was found in 69 % and 56 % of the samples, respectively. NY-ESO-1 was statistically higher expressed in samples from metastatic lesions as compared to samples from primary tumors. Nuclear expression of YAP1 and TAZ was observed in 92 % and 51 % of the samples, respectively. CXCR4 was expressed in the majority of the samples (82 %). BRD9 was highly expressed in all specimens. No prognostic role could be identified for any of the investigated proteins. CONCLUSION: This study is a comprehensive study providing real-world data on the expression of several actionable proteins in a large proportion of SynSa samples. All evaluated markers were expressed in a clinically meaningful proportion of cases represented in our TMA, supporting the relevance of ongoing preclinical and clinical research with novel agents directed against these targets.

Sarcomas of synovial origin in dogs: An updated review.

The purpose of this review is to clarify the terminology, possible cells of origin, and expected behavior of the most common synovial tumors in dogs. The synovial lining consists of 2 cell types, type A and type B. Type A synoviocytes are histiocytes of bone marrow origin that are immunoreactive with antibodies against typical markers of histiocyte origin, such as CD18, Iba-1, and CD204. Certain breeds and dogs with previous injury to a joint, especially cranial cruciate ligament rupture, are predisposed to synovial histiocytic sarcoma. Type B synoviocytes are mesenchymal cells that produce synovial fluid. There are no specific markers of type B synoviocytes, but based on their gross and microscopic appearance, synovial myxosarcomas (previously considered synovial myxomas) are presumed to be of type B synoviocyte origin. These can infiltrate into surrounding tissues, but are slow-growing and rarely metastasize, and then only to regional lymph nodes. Synovial histiocytic sarcomas and myxosarcomas can cause lysis in multiple bones surrounding the joint, but they have different prognoses and require histopathology and sometimes immunohistochemistry to diagnose them. Synovial sarcoma and synovial cell sarcoma are terms used in the human medical literature for a tumor that is not of synovial origin; these terms should not be used in veterinary medicine.

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.

Synovial Sarcoma in the Right Thigh of a 25-Year-Old Male: A Case Report.

In this article, we describe the diagnosis and surgical treatment of synovial sarcoma within the right thigh of a 25-year-old male. Our article aims to demonstrate successful treatment through wide local excision and rotation flap reconstruction, emphasizing the noteworthiness of comprehensive surgical planning and postoperative care. Postoperative care guaranteed satisfactory healing and appendage functionality, with a follow-up plan to monitor for recurrence. This case underscores the need for individualized treatment approaches and highlights the significance of multidisciplinary care for overseeing aggressive tumors like synovial sarcoma. The findings contribute to the ongoing refinement of surgical procedures and postoperative protocols to improve patient results.