Usefulness of SS18-SSX antibody as a diagnostic marker for pulmonary metastatic synovial sarcoma.

BACKGROUND: The novel SS18-SSX fusion-specific antibody is reported to have high sensitivity and specificity for the diagnosis of primary synovial sarcoma (SS), which often metastasizes to the lung. Thus far, no study has validated the diagnostic efficacy of SS18-SSX antibody for pulmonary metastatic SS. Therefore, we aimed to investigate the usefulness of the SS18-SSX antibody in the diagnosis of pulmonary metastatic SS. METHODS: We evaluated the immunohistochemistry of SS18-SSX fusion-specific antibody (E9X9V) in 10 pulmonary metastatic SS cases and the corresponding five primary sites (four limbs and one mediastinum) in five patients, for whom SS was already diagnosed and confirmed by fluorescence in-situ hybridization in the metastatic and primary sites, and in 93 clinical and histologic mimics including 49 non-SS, pulmonary metastatic sarcomas, 39 primary lung cancers, and five intrathoracic solitary fibrotic tumors. All specimens were surgically resected at Shinshu University Hospital during 2001-2019. For primary and metastatic SS, we also evaluated SS18-SSX immunohistochemistry using needle biopsy and touch imprint cytology specimens from the primary site. RESULTS: SS18-SSX staining was diffusely-strongly positive in all 10 pulmonary metastatic SS cases and the corresponding five primary sites; whereas, it was negative in all 93 clinical and histologic mimics (100% sensitivity and 100% specificity). Further, SS18-SSX staining was also sufficiently positive in the biopsy and cytology specimens. CONCLUSIONS: Immunohistochemistry of the SS18-SSX fusion-specific antibody is useful for the differential diagnosis of pulmonary metastatic SS in clinical practice. This simple and reliable method has the potential to replace traditional genomic tests. However, further studies are warranted in this regard.

Primary Renal Synovial Sarcoma and Clinical and Pathological Findings: a Systematic Review.

PURPOSE OF REVIEW: To update epidemiological, diagnostic, and therapeutic information on primary synovial sarcoma of the kidney. RECENT FINDINGS: A total of 96 studies were analyzed; age at presentation was 38.6±14.2 years, predominant location of tumor was right kidney; frequent reported symptoms at diagnosis were hematuria and pain. For definitive diagnosis, cytogenetic technique was used. Detected oncogene was available in 37.8% cases with fusion of SS18-SSX in most patients. Surgery is treatment of choice, with adjuvant chemotherapy; most frequently ifosfamide-based associated with doxorubicin or epirubicin. Overall median survival was 34 months. Mortality was 29% of the cases which reported death and the recurrence rate was 39.8%. Risk of death was increased in patients with metastases at diagnosis Primary RSS occurs more often in young men. RSS often presents with symptoms and in an advanced stage. Surgical treatment is the most commonly used and chemotherapy for advanced or recurrent treatment.

Primary cardiac synovial sarcoma: a clinicopathological, immunohistochemical, and molecular genetics study of five clinical cases.

BACKGROUND: Primary cardiac synovial sarcoma was an exceedingly rare tumor that less reported. The study investigated the clinicopathologic, immunohistochemical, and molecular features of primary cardiac synovial sarcoma. METHODS: A total of five cardiac synovial sarcoma cases were assessed and reviewed using H&E, immunohistochemical and fluorescence in situ hybridization staining methods. Clinicopathological data were retrospectively analyzed and followed up. RESULTS: The cases occurred in four males and one female ranging in age from 23 to 48 years (mean, 32 years). The tumors were grossly large and solid (7.4-13.7 cm; mean 8.6 cm). Microscopically, clinical cases were biphasic (n = 2) and monophasic (n = 3) types and were diffusely immunoreactive for EMA, vimentin, and BCL-2. All cases demonstrated SS18 rearrangement by fluorescence in situ hybridization staining. Clinically, three patients died within 1 year after surgery, while one patient had bone metastasis and still carried the disease. One last patient underwent a heart transplant and survived without evidence of the disease. CONCLUSION: Cardiac synovial sarcoma was an aggressive tumor whose differentiation may be a continuous and complex morphologic spectrum. SS18 rearrangement demonstration by fluorescence in situ hybridization was decisive in our study for differential diagnosis of cardiac synovial sarcoma and other tumors. Cardiac synovial sarcoma usually endured poor survival rates. Patients in advanced stages may undergo heart transplantation as a means of improving their survival rates.

Primary synovial sarcoma of the lung: a rare presentation, diagnostic dilemma and review of literature.

Primary synovial sarcoma of the lung (PSSL) is a rare tumour with only 0.5% incidence among other primary malignant lung tumours. Published medical literature regarding the natural history treatment protocol and clinical outcomes of PSSL remains limited. Here, we present a case of a 39-year-old man with primary synovial sarcoma with long-term follow-up, which was initially viewed as a metastasis from another unknown site. After evaluating histopathologically from the specimen post left lung metastasectomy and ruling out any other site for neoplastic changes, the diagnosis of PSSL was confirmed. Furthermore, this article reviews the literature and discusses various aspects of PSSL, including clinical presentation, radiological imaging and pathological characteristics, diagnostic dilemma, management and prognosis. This paper serves to provide an update and aims to enhance the understanding of PSSL. Timely diagnosis and treatment are imperative to achieve improved outcomes.

Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States.

BACKGROUND: Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials. METHODS: In this multi-center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first-line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: At start of first-line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first-line therapy for SS was 24.7 months (95% CI, 20.9-29.4) and 7.5 months, respectively (95% CI, 6.4-8.4). Median OS and median PFS from start of first-line therapy for MRCL was 29.9 months (95% CI, 27-44.6) and 8.9 months (95% CI 4.5-12.0). CONCLUSIONS: To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real-world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature.

Tumor mutation burden and checkpoint immunotherapy markers in primary and metastatic synovial sarcoma.

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.

Cinematic rendering for three-dimensional reconstructions of the chest wall: a new reality.

Computed tomography with multiple detectors and the advancement of processors improved rendered images and three-dimensional reconstructions in clinical practice. Traditional axial slices form non-intuitive images because they are seen in only one plane. The three-dimensional reconstructions can show structures details and diseases with complex anatomy in different perspectives. Cinematic rendering is a newly three-dimensional reconstruction technique, already approved for clinical use, which can produce realistic images from traditional computed tomography data. The algorithm used is based on light trajectory methods and the global lighting model, which simulate thousands of images from all possible directions. Thus, the technique shapes the physical propagation of light and generates a realistic three-dimensional image with depth, shadows and more anatomic details. It is a multidimensional rendering acquired through complex lighting effects. The aim of this article was to show the advance of three-dimensional technology with the cinematic rendering in images exams of the thoracic wall.

Cinematic rendering for three-dimensional reconstructions of the chest wall: a new reality / Uma nova realidade: renderização cinematográfica para reconstruções tridimensionais da parede torácica

ABSTRACT Computed tomography with multiple detectors and the advancement of processors improved rendered images and three-dimensional reconstructions in clinical practice. Traditional axial slices form non-intuitive images because they are seen in only one plane. The three-dimensional reconstructions can show structures details and diseases with complex anatomy in different perspectives. Cinematic rendering is a newly three-dimensional reconstruction technique, already approved for clinical use, which can produce realistic images from traditional computed tomography data. The algorithm used is based on light trajectory methods and the global lighting model, which simulate thousands of images from all possible directions. Thus, the technique shapes the physical propagation of light and generates a realistic three-dimensional image with depth, shadows and more anatomic details. It is a multidimensional rendering acquired through complex lighting effects. The aim of this article was to show the advance of three-dimensional technology with the cinematic rendering in images exams of the thoracic wall.

RESUMO A tomografia computadorizada com os múltiplos detectores e o avanço dos processadores melhoraram as imagens renderizadas e as reconstruções tridimensionais na prática clínica. Os cortes axiais tradicionais formam imagens não intuitivas, pois são vistas em apenas um plano. Já as reconstruções tridimensionais podem exibir detalhes anatômicos em diferentes perspectivas das estruturas e de doenças com anatomia complexa. A renderização cinematográfica é uma técnica de reconstrução tridimensional recentemente introduzida, já aprovada para uso clínico, que pode produzir imagens realistas a partir de dados tradicionais da tomografia computadorizada. O algoritmo usado é baseado em métodos de trajetória da luz e no modelo de iluminação global, os quais simulam milhares de imagens de todas as direções possíveis. Assim, a técnica molda a propagação física da luz e gera uma imagem tridimensional realista, com profundidade, sombras e mais detalhes da alteração anatômica. É uma renderização multidimensional adquirida por efeitos de iluminação complexos. O objetivo deste artigo foi mostrar o avanço da tecnologia tridimensional com a renderização cinematográfica nos dos exames de imagens da parede torácica.

Treatment of cardiac synovial sarcoma: experience of two cases.

BACKGROUND: Primary heart sarcomas are exceedingly rare tumors. Among primary cardiac sarcomas, synovial sarcoma is one of the rarest, involving cardiac cavities or pericardium. CASE PRESENTATION: Two cases of synovial sarcoma are presented with the clinical course and therapy. Both cases were treated with surgery and chemo/radiotherapy. Interestingly, one of the patient, a 52-year-old male with an intracardiac synovial sarcoma, undergone a SynCardia total artificial heart implantation, but died for multiple pulmonary metastases waiting for transplantation. CONCLUSION: Complete surgical resection of cardiac synovial sarcoma is the gold standard of therapy, though rarely possible. Although guidelines for the treatment are not well established, due to limited number of cases reported, chemotherapy and radiotherapy are frequently administered and seem to prolong mean patient's survival. Cardiac transplantation could be considered in selected cases.

Synovial Sarcoma Is Not Associated With a Higher Risk of Lymph Node Metastasis Compared With Other Soft Tissue Sarcomas.

BACKGROUND: Reported rates of the incidence of lymph node metastasis in soft tissue sarcoma vary considerably. Many are based on single-institution series and small patient populations. Certain sarcoma subtypes, including synovial sarcoma, have been associated with a higher risk of lymph node involvement. Most single centers have insufficient numbers of patients to assess lymph node metastasis accurately, but larger national databases may allow a more accurate estimation. QUESTIONS/PURPOSES: We queried a large national database and asked the following questions: (1) What proportion of patients with soft tissue sarcoma have lymph node metastasis and distant metastasis? (2) What histologic subtypes are associated with increased risk of nodal metastasis? (3) What is the impact of lymph node metastases and histologic subtype on survival? (4) Does lymph node excision improve survival of patients with soft tissue sarcoma? METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program is a national database that covers a geographic cross-section representing approximately 28% of the US population across demographic groups. Using the SEER database, we identified 15,525 adults diagnosed with histologically confirmed soft tissue sarcoma from 2004 to 2013. Proportions of patients with lymph node or distant metastases were calculated using descriptive statistics. Overall survival was computed using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazard regression to calculate the association of lymph node metastasis with overall survival while controlling for patient age, sex, race, tumor size, and tumor location. RESULTS: A total of 820 of 15,525 patients had lymph node metastasis at the time of diagnosis, yielding an overall proportion of 5.3% (95% confidence interval [CI], 4.9%-5.6%). Histologic subtypes that most frequently developed nodal metastasis were rhabdomyosarcoma, clear cell sarcoma, epithelioid sarcoma, and myxoid/round cell liposarcoma. Despite frequent reports regarding its association with lymph node metastasis, the proportion of patients with lymph node metastasis among 885 patients with synovial sarcoma (4.2%) was not different from the proportion with nodal metastasis in the overall soft tissue sarcoma population. For all soft tissue sarcomas, distant metastatic disease was present at diagnosis in 1869 (12%) patients (95% CI, 11.5%-12.6%). After controlling for relevant covariates, lymph node metastasis was associated with poorer overall survival (hazard ratio [HR], 1.34; 95% CI, 1.22-1.48; p < 0.001) as was distant metastasis (HR, 2.87; 95% CI, 2.66-3.09; p < 0.001). When comparing the subgroup of patients with positive lymph nodes, lymphadenectomy in conjunction with local excision/limb salvage was associated with the highest overall 5-year survival (HR, 0.46; 95% CI, 0.31-0.67; p < 0.001). CONCLUSIONS: In clarifying the overall proportion of patients with soft tissue sarcoma with nodal metastases, the current study indicates that lymph node metastases occur at a higher proportion than previous studies have suggested and that synovial sarcoma is not associated with a higher risk of lymphatic spread compared with soft tissue sarcoma overall. Patients with lymph node metastases are associated with poorer survival than those without metastases. Further investigation is needed to clarify the apparent improved overall survival after lymphadenectomy in the setting of nodal metastasis from soft tissue sarcoma. LEVEL OF EVIDENCE: Level II, prognostic study.

Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

First-in-Human Treatment With a Dendritic Cell-targeting Lentiviral Vector-expressing NY-ESO-1, LV305, Induces Deep, Durable Response in Refractory Metastatic Synovial Sarcoma Patient.

Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1. LV305 is currently being evaluated in phase 1 and 2 trials in metastatic recurrent cancer patients with NY-ESO-1 positive solid tumors as a single agent and in combination with anti-PD-L1. Here we report on the first patient treated with LV305, a young woman with metastatic, recurrent, therapy-refractive NY-ESO-1 synovial sarcoma. The patient developed a robust NY-ESO-1-specific CD4 and CD8 T-cell response after 3 intradermal injections with LV305, and subsequently over 85% disease regression that is continuing for >2.5 years posttherapy. No adverse events >grade 2 occurred. This case demonstrates that LV305 can be safely administered and has the potential to induce a significant clinical benefit and immunologic response in a patient with advanced stage cancer.

Synovial metastasis of the knee in a KRAS mutant rectal adenocarcinoma patient.

Synovial metastasis is an unusual entity in solid tumours and only a few cases have been reported in the literature. We report a case of synovial metastasis of the knee in a young patient with progressive rectal adenocarcinoma and review previously published case reports of synovial involvement in advanced colorectal carcinomas. Synovial metastasis is just one of the multiple possibilities of differential diagnosis in patients with cancer suffering from monarthritis. Radiological tests (plain radiographs, bone scans, MRI of the joint and so forth) can be unspecific and cytological examination of the synovial fluid and/or histology of synovial biopsies is essential for a definitive diagnosis so as to tailor the best treatment for patients. Given the poor prognosis associated with these intra-articular secondaries, treatment is often limited to palliation.

Histology and grading are important prognostic factors in synovial sarcoma.

INTRODUCTION: The diagnosis of synovial sarcoma (SS) is currently based on clinical, morphological, immunohistochemical and cytogenetic data. Some of these factors such as grade and histology, specific translocations (SS18-SSX1 vs. SS18-SSX2) and the reduced expression of INI1, were proposed as prognostic variables. The aim of this study was to verify whether histological (grading and histology) and molecular (type of SSX translocation and INI1 expression) characteristics of SS influence the prognosis of the disease. MATERIAL AND METHODS: We retrospectively evaluated 196 patients affected by SS of the extremities treated at our Institution (Istituto Ortopedico Rizzoli, Bologna, Italy). All cases were histologically revised and tumor grade was assessed according to the FNLCC system. Tissue specimens were retrospectively evaluated to check for SS18-SSX fusion type and INI1 expression. RESULTS: Most SS were monophasic, 28% were biphasic. Eighty tumors (41%) were grade 3. Sixty percent harbored SSX1 translocation, 40% SSX2; 51% maintained the expression of INI1. Sarcoma specific survival (OS) was 56.6% at 5 years and 46.9% at 10 years. Prognosis was worse in those patients monophasic SS (p = 0.011) as in those with a grade 3 tumors (p = 0.083). No correlation was found neither between SSX fusion type nor INI1 expression and survival. LR-free survival was 78.9% at 5 years and 75.9% at 10 years. A higher LR rate was observed in tumors with SSX2 translocation and (p = 0.049) in grade 3 SS (0 = 0.028). DISCUSSION: Our data confirm that not all cases of SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Soft Tissue Neoplasms Causing Apparent Venous Thoracic Outlet Syndrome.

Venous thoracic outlet syndrome (vTOS) usually results from compression of the subclavian vein classically as a result of narrowing of the costoclavicular space. We report 2 rare cases of soft tissue neoplasms resulting in apparent vTOS. The first case is a 46-year-old female with a 2-year history of intermittent unilateral shoulder pain, who was initially diagnosed with intervertebral disk herniation. Cervical fusion was performed; however, her symptoms progressed and she additionally developed paresthesias and venous congestion. Computed tomography (CT) angiogram demonstrated a 13-cm-encapsulated mass within the subscapularis muscle compressing the axillary vein. Radiological findings suggested lipoma. She subsequently underwent complete resection via a transaxillary approach with extension along the lateral border of the latissimus. Final pathology confirmed an intramuscular lipoma. The second case is a 21-year-old female who presented with acute onset of unilateral chest wall pain, palpable nodularity, and venous congestion. CT chest showed pulmonary embolism and an anterior chest wall mass. An initial attempt at resection was aborted due to proximity of the mass to the subclavian vein. The mass enlarged on serial imaging, measuring 3.8 cm in greatest dimension. Additionally, tumor thrombus was seen, and a subsequent ultrasound-guided biopsy was positive for high-grade synovial sarcoma. Positron emission tomography scan showed a pulmonary nodule that was resected thoracoscopically with pathology confirming metastatic synovial sarcoma. Subsequently, she underwent neoadjuvant chemoradiation followed by successful resection of the chest wall mass. An extended infraclavicular approach with a secondary transaxillary incision was utilized to achieve adequate exposure and margins. Final pathology was consistent with preoperative biopsy. Venous reconstruction was not needed. Although rare, an extrinsic mass as a cause of apparent TOS should be in the differential diagnosis. Surgical approach is based on tumor type, location, and proximity to the neurovascular bundle.