Diagnosis Of Synovial Sarcoma Research Articles

WITHDRAWN: A rare case of high-grade synovial sarcoma of the hindfoot

Aim of the workto report our personal experience on hindfoot reconstruction by means of anterolateral thigh (ALT) flap after radical resection of a high-grade synovial sarcoma. Methodspatient underwent clinical and instrumental assessments, and a biopsy of the lesion confirmed the diagnosis of synovial sarcoma of the hindfoot. A multidisciplinary team was required to decide the better therapeutic strategy. ResultsAfter radical tumor mass resection, the coverage of the large skin gap was achieved with an ALT flap. No recurrences were observed during the follow-up. Today, after eighteen months after surgical treatment, the patient can walk independently with no major limitations in everyday life. Conclusionsthe complex management of this rare disease requires the presence of a reference center for foot and ankle surgery, and a multidisciplinary team including expert orthopedics and plastic surgeons, as well as oncologists, to ensure an optimal and correct treatment of the disease.

Primary renal synovial sarcomas diagnosed by a novel fusion gene with the fusion site involving exons of SS18 and SSX2: a case report

Abstract Objectives Primary renal synovial sarcoma (PRSS) is an uncommon malignancy with diagnostic challenges and poor prognosis. Research on PRSS is limited, primarily based on case reports, leading to a lack of widely recognized effective treatment options. This article reports a case of primary renal synovial sarcoma diagnosed using a novel fusion gene with a fusion site involving the SS18 and SSX2 exons. Case presentation A 34-year-old male, presented with intermittent right upper abdominal pain. Abdominal CT revealed an isolated mass in the upper pole of the right kidney, which was initially diagnosed as renal cell carcinoma. The patient underwent radical right nephrectomy, and postoperative histopathological examination confirmed the diagnosis of synovial sarcoma, and immunohistochemistry supported the diagnosis. Further detection through RT-PCR and DNA sequencing confirmed the presence of the SS18-SSX2 fusion gene. Despite the recommendation for adjuvant therapy, the patient refused chemotherapy and other treatments and succumbed to systemic metastasis. Conclusions This case highlights the diagnostic challenges and aggressive nature of PRSS. The novel fusion gene with the fusion sites SS18: exon9 and SSX2: exon5 has important implications for the diagnosis of primary synovial sarcoma of the kidney. Further research is warranted to explore novel therapeutic strategies and improve patient outcomes in PRSS.

Synovial sarcoma: the misdiagnosed sarcoma.

Synovial sarcoma is a rare and highly malignant soft tissue sarcoma. The inconspicuous and diversity of its early symptoms make it a highly misdiagnosed disease. The management of synovial sarcomas is challenging as they are rare and have a poor prognosis. Early and correct diagnosis and treatment are critical for clinical outcomes. Misdiagnosis or delayed diagnosis can have devastating consequences for the patient. The detection of SS18 gene rearrangement is considered a powerful tool in establishing the diagnosis of synovial sarcomas. Biopsies and testing for gene rearrangements are recommended for all patients in whom SS cannot be excluded. Surgery is the mainstay of treatment for synovial sarcomas. Neoadjuvant/adjuvant radiotherapy is recommended for patients with big tumors (>5 cm) or positive resection margins, and neoadjuvant/adjuvant chemotherapy is recommended for patients with high-risk tumors or advanced diseases. This article reviews synovial sarcomas from the perspectives of clinical and radiological presentation, histological and cytogenetic analysis, differential diagnosis, treatment, and prognosis.

Primary Monophasic Omental Synovial Sarcoma in Nulliparous Female: A Case Report

Synovial Sarcoma (SS) is an uncommon soft-tissue malignancy that primarily occurs near tendon sheaths and bone joints. Its primary intra-abdominal location is infrequent and characterised by non specific clinical signs. The mainstay of treatment remains wide local excision with negative margins. Hereby the authors report a rare case of monophasic omental SS in a 30-year-old nulliparous female who presented with chief complaints of an enlarging lump in the right abdominopelvic region over the past year and constipation for three months. The mass was non mobile and non tender. The rest of the physical and laboratory examinations were normal. She has a history of diagnostic laparoscopic excision (for the same complaint) of bilateral adnexal masses with right salpingectomy done three months ago in an outside set-up where histopathology diagnosed the mass as a low-grade fibromyxoid tumour. Presently, Contrast- enhanced Magnetic Resonance Imaging (CEMRI) revealed a large lobulated heterogeneous mass of 19.5×15.4×20 cm extending into mesorectal fat and encasing the sigmoid colon, rectosigmoid junction, uterus, and bilateral ovaries. The patient was taken for emergency surgery as she started displaying symptoms of acute obstruction. Debulking surgery (R2 resection) with ileostomy was performed. Histopathology and immunohistochemistry confirmed the diagnosis of monophasic SS. The patient was started on doxorubicin and has completed three cycles of chemotherapy. SS is an infrequent entity with high mortality rates. The main course of treatment is surgery with healthy resection margins. Long-term follow-up is required due to the high recurrence rate.

Synovial Sarcoma of the Descending Colon: Report of a Rare Case and Review of the Literature

Abstract Introduction/Objective Synovial Sarcoma is a mesenchymal malignancy that occurs primarily in the deep soft tissue near large joints of the extremities in young adults. Synovial sarcoma of the gastrointestinal tract is extremely rare. There is not enough literature to establish a consensus on management and treatment for colorectal synovial sarcoma. Methods/Case Report An 85-year-old male preresented with a positive cologuard test and the colonoscopy revealed a 12 mm polyp in the descending colon. Polypectomy was preformed. Histological examination exhibits spindle cell proliferation with fascicular growth pattern and with small nucleoli. There are collagen deposition, variable size of thick wall vessels and mixed inflammatory cells including lymphocytes, eosinophils and neutrophils in the background. Mitosis are identified. Immunohistochemical stains show tumor cells are negative for CD34, S100, DOG1, CD117, STAT6, Bcl-2, Desmin, and AE1/AE3, and focal positive for EMA, SMA and ALK. Immunohistochemical stain for SS18-SSX fusion protein is positive. Archer fusionplex targeted RNA sequencing (M23-1377) showed SS18:SSX2 fusion. A structural genomic alteration between the SS18 and SSX2 genes is detected [t(18;X)(q12.1;p11.22)]. These findings confirmed the diagnosis of synovial sarcoma. Results (if a Case Study enter NA) NA Conclusion Here we report a rare case of descending colon primary synovial sarcoma. Synovial sarcoma is generally considered as an aggressive and high-grade lesion with metastatic potential and its management is different from other colorectal neoplasms. This case report emphasies a wide differential diagnosis for colorectal lesions and prompt diagnosis and early management is important for better patient outcome.

Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology-A Potential Diagnostic Pitfall.

Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.

Immunocytochemistry as an Ancillary Technique in the Cytologic Diagnosis of Synovial Sarcoma: Lock With Cell Block

Introduction: Synovial sarcomas are rare tumors accounting for approximately 5-10% of soft tissue sarcomas. For synovial sarcomas that arise at unusual locations, cytologic diagnosis is challenging despite characteristic cytomorphologic features.
 Material and Methods: The use of ancillary diagnostic procedures such as immunocytochemistry (ICC) using cell blocks and molecular genetic techniques using aspirated material help in the confirmation of diagnosis. During the period of 18 months from Nov 16 to Feb 18 we reported three cases of SS that occurred in rare locations with the help of ICC on cell blocks in 2 cases and IHC in the third case.
 Results: Cells arranged in bundles, perivascular arrangement, tight clusters, acini & singly. Cells are elongated, oval to spindle, presence of uni or bipolar cytoplasmic processes with mildly pleomorphic , hyperchromatic nuclei & fine granular chromatin. TLE1 was positive in all 3 cases.
 Conclusion: TLE1 marker is an extremely useful marker that distinguishes SS from other cytological & histological mimics.
 The objective of the present study was to call attention and also highlight the variable cytology of synovial sarcoma arising at rare locations. Furthermore, we discuss use of adjunctive ICC on cell blocks that help to lock the diagnosis.

Synovial sarcoma: cytopathology of 51 cases highlighting the application of ancillary molecular testing.

Among sarcomas, synovial sarcoma (SS) is defined by its unique SS18 cytogenetic translocation. Fine needle aspiration (FNA) biopsy is in a key position to exploit this uniqueness for diagnostic purposes. Our cytopathology files were searched for examples of SS with histopathologic verification. FNA biopsy, imprint smears, and core needle biopsy (CNB) were performed using standard techniques. Fifty-one cases from 49 patients (male/female ratio, 1:1; age range, 12-79 years; mean age, 40 years) met the inclusion criteria. Of the 51 cases, 44 (86%) were FNAs, 6 were cytology imprints, and 1 was pleural fluid. Eleven aspirates had concurrent CNB. All cases had tissue confirmation. The biopsy sites included extremities (n = 24; 47%), trunk (n = 12; 24%), lung (n = 8; 16%), head or neck (n = 6; 12%), and pleural fluid (n = 1; 2%). The aspirates were from primary (n = 36; 71%), metastatic (n = 12; 24%), and recurrent (n = 3; 5%) neoplasms. The cytologic diagnoses were SS (69%), suspicious for SS (12%), malignancy (10%), spindle cell neoplasm (4%), and malignancy other than SS (6%). In general, smears and imprints contained dense cell aggregates and single cells composed of a monotonous population having fusiform, rounded, or ovoid banal nuclei and scant cytoplasm. Poorly differentiated SS showed both large epithelioid cell and small cell cytomorphology. When performed, SS18 immunohistochemical and genetic testing was positive in all 19 FNA and 3 CNB cases. When coupled with appropriate ancillary testing, FNA biopsy allows for a specific, accurate diagnosis of SS in most cases.

SS18-SSX Antibody: A Useful Tool to Save Time and Reduce Costs in Synovial Sarcoma Diagnosis. Proposal of a Novel Diagnostic Algorithm.

Synovial sarcoma is a rare malignant mesenchymal neoplasm mostly affecting young adults, characterized by a specific translocation which results in the fusion of the SS18 gene on chromosome 18 with one of the three highly homologous SSX genes on chromosome X. Its morphological diagnosis, especially in monophasic or poorly differentiated variants, can be challenging because histological features often overlap with other malignant mesenchymal tumors. Until recently, the differential diagnosis mostly relied on the use of cytogenetic or molecular analyses to detect the specific t(X;18)(p11;q11) translocation, thus virtually restricting its correct identification to referral centers with a high histological and molecular pathology workflow. The recently commercialized highly sensitive and fusion-specific SS18-SSX antibody has significantly improved the approach to these tumors, representing a relatively cheap and easy to access tool for synovial sarcoma diagnosis. Through a retrospective analysis of 79 synovial sarcomas and histological mimickers, this study confirms the usefulness of the SS18-SSX antibody in the diagnosis of synovial sarcoma, particularly focusing on its application in the pathological response evaluation after neoadjuvant treatment as well as its time- and cost-saving advantages. Finally, we here propose a new diagnostic algorithm to apply into the routine practice.

The impact of hispanic ethnicity in presentation and outcomes of patients with synovial sarcoma.

e18682 Background: Synovial sarcomas (SS) harbor a specific, balanced, reciprocal translocation t(X;18) leading to the oncogenic SS18-SSX fusion. It accounts for 5-10% of all soft tissue sarcomas, and there is a lack of information regarding the impact of race and ethnicity on its presentation and outcomes. Florida is currently not included in the SEER database, and it is the US's ninth-most diverse population, with a diversity index of 64.1% and with the sixth-highest Hispanic population among all states. Sylvester Comprehensive Cancer Center (SCCC) and Memorial Healthcare System (MHS) are two large oncology centers in South Florida that provide care for this rare type of tumor. We aimed to identify the impact of Hispanic ethnicity in SS. Methods: We retrospectively reviewed all patients with a confirmed diagnosis of SS between January 2003 and January 2022 in SCCC and MHS. All data were retrieved from electronic medical records. SPSS Statistics was utilized, Fisher exact test and log-rank test were used for analysis. A two-sided p < 0.05 was considered statistically significant. Results: A total of 73 patients had a pathologically confirmed diagnosis of SS, with information regarding ethnicity, during the time period evaluated, 45.3% were Hispanic, and 54.7% were non-Hispanic. The Hispanic group was comprised mainly of female patients (66%) with a median age of diagnosis of 44 years old, these findings were similar in the non-Hispanic group, where 55% were women, and the median age at diagnosis was 42 years old. Fewer patients identified themselves as Black within the Hispanic group (3%) compared to the non-Hispanic (22%) (p = 0.016). The most common site of primary disease was the extremity in both groups (Hispanic 63% vs non-Hispanic 75%) (p = 0.384). Most tumors were diagnosed with a size bigger than 5cm (Hispanic 57% vs non-Hispanic 65%) (p = 0.577) and with pathology reporting a monophasic SS (Hispanic 45% vs non-Hispanic 50%) vs biphasic or poorly differentiated (p = 0.061). Non-Hispanics had more poorly differentiated tumors (Hispanic 3% vs non-Hispanic 17.5%) (p = 0.054). Hispanic patients did have fewer cases of metastatic disease at diagnosis (Hispanic 9% vs non-Hispanic 32%) (p = 0.023). The median overall survival (mOS) among Hispanic patients was not reached in our study, and mOS among the non-Hispanic patients was 5 years (p = 0.099). Conclusions: In our study, the patients more commonly presented with large tumors ( > 5cm) in the extremity and monophasic histology, regardless of their ethnicity. Non-Hispanic patients more often had poorly differentiated tumors, metastatic disease at diagnosis, and a trend toward worse mOS. This study had limited power due to the limited number of patients, and further studies are needed to identify the presence of disease-related differences in these populations.

Novel characteristics for immunophenotype, FISH pattern and molecular cytogenetics in synovial sarcoma

As a rare and highly aggressive soft tissue sarcoma, the new immunophenotype, atypical FISH pattern and relevant molecular cytogenetics of synovial sarcoma (SS) remain less known, although it is characteristically represented by a pathognomonic chromosomal translocation t (X; 18) (p11.2; q11.2). Methodologically, the morphology was retrospectively analysed by using H&E staining, and immunohistochemical features were investigated by using markers that have been recently applied in other soft tissue tumors. Moreover, FISH signals for SS18 and EWSR-1 break-apart probes were examined. Finally, cytogenetic characteristics were analysed via RT-PCR and Sanger sequencing. Consequently, nine out of thirteen cases that were histologically highly suspected as SS were finally identified as SS via molecular analysis. Histologically, nine SS cases were divided into monophasic fibrous SS (4/9), biphasic SS (4/9) and poorly differentiated SS (1/9). Immunohistochemically, SOX-2 immunostaining was positive in eight cases (8/9) and PAX-7 immunostaining was diffusely positive in the epithelial component of biphasic SS (4/4). Nine cases showed negative immunostaining for NKX3.1 and reduced or absent immunostaining for INI-1. Eight cases showed typically positive FISH signalling for the SS18 break-apart probe, whereas one case exhibited an atypical FISH pattern (complete loss of green signalling, case 2). Furthermore, the SS18-SSX1 and SS18-SSX2 fusion genes were identified in seven cases and two cases, respectively. The fusion site in 8 out of 9 cases was common in the literature, whereas the fusion site in case 2 was involved in exon 10 codon 404 in SS18 and exon 7 codon 119 in SSX1 (which has not been previously reported), which notably corresponded to the complete loss of green signalling in the FISH pattern. Additionally, FISH analysis of the EWSR-1 gene in nine SS cases demonstrated aberrant signalling in three cases that were recognized as a monoallelic loss of EWSR-1 (1/9), an amplification of EWSR-1 (1/9) and a translocation of EWSR-1 (1/9). In conclusion, SS18-SSX fusion gene sequencing is obligatory for a precise diagnosis of SS when dealing with a confusing immunophenotype and atypical or aberrant FISH signalling for SS18 and EWSR-1 detection.

Abstract 6071: Whole-exome RNA sequencing of metastatic synovial sarcomas reveals heterogeneous transcriptomic profile and targetable co-alterations: Cohort study from the French Sarcoma Group

Abstract Introduction: Synovial Sarcoma (SS) is a rare and aggressive disease that predominantly occurs in young adult. SS are characterized by a pathognomonic t(X:18) translocation leading SS18: SSX1/2/4 fusion. Small studies (n<100) described molecular background beyond this fusion in patients and the transcriptomic profile of SS remains poorly known. The aim of our study is to provide a large cohort analyzing transcriptomic and co-alterations to better understand and treat SS. Methods: We present a clinico-biological cohort study including all adult patients with histologically confirmed diagnosis of afvanced SS from January 2000, registered in the French Sarcoma database (NETSARC+) and with available formalin-fixed paraffin embedded (FFPE) archival tumor samples and clinical data. FFPE tumor samples were analyzed by dedicated whole-exome RNA-sequencing (WERS) to assess transcriptomic, small nucleotide variation (SNV) and fusions. Results: 122 patients (133 samples) met the study criteria, including 11 patients with paired primary-metastatic tumor samples. Clinical characteristics (age, sex, tumor grade, primary and metastasis site distribution) were consistent with expected SS population. The SS18:SSX1/2/4 fusion was found in all patient (90% by WERS and if negative, by FISH). Unsupervised analyses of transcriptomic data by principal component analyses, hierarchical sample clustering or UMAP revealed heterogeneity in gene expression. Clinical factors (age, sex, grade, tumor type, complete response to treatment, survival) did not correlate with transcriptomic profiles. Immune cell analyses confirmed a low infiltration of immune cells, notably poor in CD8+ T cells. Cancer testis antigens such as NYESO-1, MAGE-A4 were both expressed with a heterogeneous co-expression of other CTAs across samples. In the 11 primary-metastatic paired- samples, no gene pathway was found differentially expressed between primary and metastatic samples cohort with the exception of lung tissue specific genes. Comparing chemotherapy-naïve versus pre-treated samples did not identify differential expression of specific genes across samples. Single Nucleotide Variant analyses was reliable on 84% FFPE samples and revealed an overall low Tumor Mutational Burden with some samples harboring canonical oncogene pathogenic mutations of BTK, RAS, NF1, RB1 as well as in DNA repair pathway(15% spanning over ATM ATR,CHK2, BRCA1/2 PALB2 CHK2, FANCM, RAD51), PI3K pathways (PI3KCA E545K) and other poorly described in SS. Conclusion: Investigating the largest cohort of metastatic SS by whole-exome RNA-sequencing, revealed Synovial Sarcoma, usually classified as “simple genomic sarcoma” is a translocation-related sarcoma harboring heterogeneous transcriptomic and numerous SNV co-alterations including targetable mutations. Citation Format: Helene Vanacker, Mehdi Brahmi, Yannick Le Meitour, Julien Bollard, Valery Attignon, Alexandra Meurgey, Myriam Jean-Denis, Laurie Tonon, Shibani Pokras, Erika Klohe, Michael Nathenson, Kristin Blouch, Ioanna Eleftheriadou, Jean-Yves Blay, Franck Tirode, Armelle Dufresne. Whole-exome RNA sequencing of metastatic synovial sarcomas reveals heterogeneous transcriptomic profile and targetable co-alterations: Cohort study from the French Sarcoma Group. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6071.

CASE REPORT OF SYNOVIAL SARCOMA PRESENTING AS A THIGH SWELLING

Synovial sarcoma (SS) is a rare tumor arising from the mesenchymal lining and commonly arising near proximity of joint. The tumor is difficult to diagnose initially or can be misdiagnosed due to its site and slow-growing potential. This is a malignant tumor with genetic predisposition and has a poor prognosis, if metastasizes to distant organs. The current study tries to describe the clinical, histopathological and immunochemistry findings of synovial sarcoma. A case of SSs presented in our institute for surgery and histopathological examination. Relevant history was taken retrospectively and consent of the patient was also taken. The treatment modality consists of wide excision surgery, chemotherapy, and radiotherapy. In this case, a 35 years old having tumor growth involving thigh area, the excised tumor was sent to our department for histopathological examination. On HPE, monophasic spindle cell tumor was diagnosed with differential diagnosis of SS or malignant peripheral nerve sheath tumor and immunohistochemistry staining was done for further confirmation.

Unresectable Primary Tracheal Synovial Sarcoma.

Synovial sarcoma (SS) comprises less than 1% of head and neck cancers, and less than five cases of adult primary tracheal SS have been described. This case describes a patient encountered at a community-based academic hospital, and retrospective chart review was performed for data collection. A woman in her forties presented with shortness of breath due to a superior mediastinal mass found to be an unresectable primary tracheal SS. Primary treatment resorted to curative-intent radiation therapy. Subsequent metastasis required systemic chemotherapy with pazopanib. To the best of our knowledge, this is the first reported case of this nature and adds to understanding the presentation, diagnosis, natural history, and treatment outcomes of primary tracheal SS. This case was exempt from review by the institutional review board and complied with privacy policy standards.

Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma.

Synovial sarcoma is an aggressive malignancy that generally affects adolescents and young adults and is characterized by high rates of recurrence and metastasis, with a 10-year survival rate of about 50%. The fusion oncoprotein SS18-SSX, the product of a pathognomonic chromosomal translocation t(X;18), is the oncogenic driver of this sarcoma, disrupting differentiation through widespread epigenetic dysregulation. Experimental research into SS18-SSX biology has been limited by the lack of an antibody that specifically detects the endogenous fusion oncoprotein as opposed to its native SS18 or SSX components. Recently, a rabbit monoclonal antibody was developed and made commercially available, which specifically detects the fusion junction site epitope of SS18-SSX as found in at least 95% of synovial sarcomas. Here, we characterize a suite of molecular biology assays using this new antibody, both confirming existing and reporting on novel applications. We demonstrate its high sensitivity and specificity for synovial sarcoma diagnosis on patient samples through positive immunohistochemical staining on synovial sarcoma, tissue microarray, and full face sections. In addition, we demonstrate detection of the human SS18-SSX protein when expressed in a genetically engineered mouse model of synovial sarcoma. We also demonstrate nuclear staining of SS18-SSX in synovial sarcoma cells using immunofluorescence, and visualize the interaction between SS18-SSX and the BAF complex member BRG1 through a proximity ligation assay. Lastly, we confirm the interaction between SS18-SSX and promoter regions of target genes through chromatin immunoprecipitation. This antibody represents a breakthrough in sarcoma research and has value in multiple applications to expand the knowledge of synovial sarcoma biology.

Ekstremite yerleşimli sinovial sarkomun klinik sonuçları

Aim: The aim of this study is to emphasize the demographic data, follow-up results and the importance of approach to
 these tumors of synovial sarcoma, which is a rare tumor in the extremities.
 Material and Methods: In this study, twenty patients who were operated on for extremity synovial sarcoma between
 2008 and 2018 at Dr. Abdurrahman Yurtaslan Oncology Hospital were retrospectively analyzed. Demographic information,
 surgical treatments, follow-up periods, recurrence and metastases of the patients were recorded.
 Results: Twenty patients with a diagnosis of synovial sarcoma with a mean age of 32.7 (range, 13 to 66) years were included
 in this study. According to the localization, it was observed that the tumors were mostly located in the thigh (25%), cruris
 (25%) and ankle (25%). It was observed that the tumor size was 5 cm or more in 70% of the patients. While 55% (n=11) of
 the patients had metastases at the time of diagnosis (lung), recurrence developed in 25% of the patients during follow-up.
 Wide resection was performed as the primary surgical treatment in 85% of the patients, while 75% received RT, only 30%
 received CT. 25% of patients died during follow-up. The mean survival time of the patients was 109.4±8.9 months. While
 the 3-year survival rate was 90%, the 5-year survival rate decreased to 80%. There was no significant difference in survival
 times according to gender, age, side, grade, tumor size, metastasis, RT, KT and recurrence status.
 Conclusion: In conclusion, synovial sarcoma is a rare malignant soft tissue sarcoma with high grade and high metastasis capacity.
 For understanding the characteristics of synovial sarcoma, multicenter studies with a larger number of patients are needed

Primary synovial sarcoma of kidney: a rare case report with review of literature

BackgroundSynovial sarcoma is a rare type of sarcoma with a predilection for extremities in young adults. Very rarely this tumor can originate from kidney.Case presentationA 22-year-old female presented to us with complaints of right flank pain and a large mass in the right side of abdomen for the last 6 months. A provisional diagnosis of renal cell carcinoma was made and right radical nephrectomy was done. However on histopathological examination the tumor was composed of spindle cells arranged in hemangiopericytoma-like vascular pattern. Immunohistochemistry and FISH confirmed the diagnosis of synovial sarcoma of kidney. The patient had no signs of recurrence or metastasis at six months of follow-up.ConclusionRenal synovial sarcomas, though rare, should be considered as a differential in young adults who present with extremely large renal mass. Surgical extirpation is the treatment of choice. Ifosfamide- and doxorubicin-based chemotherapy can be given in non resectable and metastatic cases.

Abstract 5876: Treatment patterns among metastatic SS patients in The US Oncology Network

Abstract Objective: Synovial sarcoma (SS) is a rare sub-type of soft tissue sarcoma with limited natural history documented. The study objective was to describe characteristics and treatment patterns of metastatic SS (mSS) patients receiving systemic treatments. Methods: This was a retrospective observational cohort study in mSS patients treated in The US Oncology Network practices. Both EHR and chart review data from 2012-2019 were used. All mSS adult patients initiating systemic treatment as first-line (1L) therapy, with >2 visits were included. Patients diagnosed with or treated for other primary tumors were excluded. Demographic and clinical characteristics were reported based on index date (date of first systemic treatment initiation in the metastatic setting). Time to treatment discontinuation (TTD) and time to next treatment (TTNT) were assessed using the Kaplan-Meier method. Results: 39 adult mSS patients were identified receiving 1L systemic treatment. Of these, 25 went on to receive a 2L treatment (64%), and 16 went on to receive 3L+ treatment (41%) during the study observation period. Median age was 41.0 years, 74% male, 70% Caucasian. 25% had metastatic disease at original diagnosis of SS (vs. localized disease). 87% had metastases to lung, 25% had >1 site of metastasis. See Table 1 for treatment distributions by line and for TTD and TTNT. Conclusions: This study provides information on treatment patterns for mSS patients treated across multiple institutions within a US community oncology setting. About 2/3 of mSS patients received 2L systemic treatments. While doxorubicin and ifosfamide regimens were most common in 1L, variability exists in the 2L and onward settings, with ifosfamide and pazopanib being more frequently used than in earlier lines. Additionally, shorter TTD and TTNT with each subsequent line of therapy documents the need for effective treatment options in the 2L+ setting that can further delay progression. Funding: GSK [208280] Distribution of treatments by line Median time to discontinuation in months(95% CI) Median time to next treatment in months(95% CI) 1L systemic treatment (n=39) Doxorubicin + Ifosfamide containing regimen 14 (35.90%) 3.9 (2.2, 5.1) 9.3 (6.2, 11.1) Pazopanib alone or in combination 7 (17.95%) Docetaxel + gemcitabine 6 (15.38%) Ifosfamide monotherapy 6 (15.38%) Doxorubicin + olaratumab combination <5 Other treatment regimens including gemcitabine, trabectedin, and investigational drugs (not related to SS) <5 2L systemic treatment (n=25) Ifosfamide alone or in combination 7 (28.00%) 3.6 (1.5, 6.0) 6.7 (4.4, 11.1) Pazopanib alone or in combination 7 (28.00%) Doxorubicin containing regimen <5 Gemcitabine alone or in combination <5 Others including cisplatin containing regimen, trabectedin <5 3L+ systemic treatment (n=31 among 16 patients) Chemotherapy monotherapy* 13 (41.94%) 2.7 (1.0, 3.7) 4.6 (1.5, 9.8) Pazopanib alone or in combination 9 (29.03%) Ifosfamide alone or in combination 5 (16.13%) Chemotherapy combination (other than with pazopanib or ifosfamide) <5 *Includes dacarbazine, doxorubicin, pembrolizumab, nivolumab, IL-2, temozolomide, vinorelbine.1L, first-line therapy; 2L, second-line therapy; 3L, third-line therapy; IL-2, interleukin-2.Time to treatment discontinuation (TTD; in months) was calculated as the time interval between the initiation of each line of therapy and the last administration of that line, if there was a record of discontinuation, death or movement to the next treatment, or last administration date of the treatment if ≥120 days before the last visit date. Otherwise, patients were censored on the last administration date.Time to next treatment (TTNT; in months) was calculated as the interval between systemic treatment initiation for a given line and initiation of the next systemic treatment. Patients who did not initiate a next treatment or did not die during the study observation period were censored on the study end date, or the last visit date available in the dataset, whichever occurred first. Citation Format: Shibani Pokras, Wan-Yu Tseng, Janet Espirito, April Beeks, Charlotte Carroll, Ken Culver, Eric Nadler. Treatment patterns among metastatic SS patients in The US Oncology Network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5876.

DNA damage response pathways in synovial sarcoma.

11580 Background: Synovial sarcomas (SS) harbor a specific, balanced, reciprocal translocation t(X;18) leading to the oncogenic SS18-SSX fusion. Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and is associated with chemosensitivity. Efforts have been made to identify a genetic signature that predicts SS progression, treatment response, and survival in order to identify more accessible and effective treatments. This investigation explores the role of DDR in pathogenesis of SS. Methods: Patients with the diagnosis of SS from 2013 to 2021 within the Caris Life Science database were included in the study. A combination of NGS of DNA and RNA at a CLIA-certified laboratory (Caris Life Sciences, Phoenix, AZ) was performed on archival tumors. Homologous recombination deficiency (HRD) scores were calculated as a composite of loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions, using a positive threshold of 42. This study was approved by the University of Miami (UM)-Sylvester IRB and all the data collected was de-identified. Results: A total of 120 patients were identified with 49 of these patients from UM-Sylvester. Mean age of diagnosis on the sample was 46 years old (range of 15-86) and 45.8% were female. Among the 49 patients from UM-Sylvester, mean age was 60 years old (range of 35-84), 28 patients had a gene alteration identified (57%) and 6 of them a homologous recombination deficiency (HRD) gene (12%). A total of 63 different genes were identified with the most common TP53 (49%), LOH (12.2%), ATRX (10.2%) and RB1 (6.1%). Other HRD genes identified were MLH1 (4%) and CHEK2 (4%). There was no correlation identified between the age (15-65 vs elderly ⩾ 65 years) or the gender (female vs male) and the presence of a mutated DDR (p = 0.615; p = 0.091 respectively). Within the entire Caris database (N = 120), we identified 11 patients (N = 120, 9%) whose tumor tested positive for any DDR gene alteration. The most common were ATM (2.6%), followed by ATRX (1.6%) and CHEK2 (0.9%). The median HRD score was 22 within the sample. Conclusions: We report here the most common genes altered on molecular profile for a large cohort of SS samples. The prevalence of predicted pathogenic DDR gene mutation carriers in our cohort (9%) suggests that constitutional defects in this pathway may be associated with SS. We found higher rates of positive DDR on the UM-Sylvester cohort, and this could be associated with specifics of our population, given high frequency of Hispanic patients. Work is ongoing to associate our findings with race, ethnicity, survival and response to treatments. Work is ongoing to associate our findings with race, ethnicity, survival and response to treatments. These correlations will be reported in the final abstract. Cytotoxic therapy remains gold standard for metastatic SS, but better understanding of the molecular profile can pave way for further options, including targeted therapy and immunotherapy.

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

Prostate synovial sarcoma (SS) is extremely rare. We report a case of prostate SS diagnosed using fine-needle biopsy. The following findings were found: The serum prostate specific antigen level was low, magnetic resonance imaging shows an irregular soft tissue mass in the right posterior part of the prostate, and computed tomography examinations did not reveal any tumor at other parts of the body. Microscopy showed that the tumor cell morphology was densely arranged by interwoven short strands of deep-stained nuclear spindle cells. Immunohistochemical tests were positive for SS18-SSX and SSX. Molecular testing showed that SS18 break-apart Fluorescence In Situ Hybridization (FISH) results were positive, and a comprehensive analysis of this case was performed. Nine cases of prostate SS reported in the English literature were reviewed. In addition, the differential diagnosis, clinical treatment, and clinical prognosis of prostate SS are comprehensively described.