Synovial sarcoma is a translocation-associated soft-tissue malignancy that frequently affects adolescents and young adults. It is driven by one of the fusion oncoproteins SS18-SSX1, SS18-SSX2, or rarely, SS18-SSX4. Prognosis of patients with recurrent or metastatic disease is generally poor, and newer therapeutic strategies are needed. In this review, we present recent discoveries in the pathogenesis, diagnosis, and treatment of synovial sarcoma. We discuss potential therapeutic strategies to improve clinical outcomes in this disease.

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Background. Synovial sarcoma can present morphologically in multiple forms, including biphasic and monophasic subtypes. As a result, the histological diagnosis can sometimes be challenging. Transducin-Like Enhancer 1 (TLE1) is a transcriptional corepressor that normally is involved in embryogenesis and hematopoiesis but is also expressed in certain tumors. This systematic review examines the potential role of TLE1 as a diagnostic biomarker for the synovial sarcoma. Materials and Methods. A literature review and meta-analysis were conducted using the electronic databases Pubmed, the Cochrane Library, and Google Scholar. Thirteen studies met our eligibility criteria and were selected for in-depth analysis. Results. The mean sensitivity and specificity of TLE1 in detecting synovial sarcoma were 94% (95% CI 91%–97%) and 81% (95% CI 72%–91%), respectively, when all studies were aggregated together. The mean positive predictive value (PPV) of TLE1 was 75% (95% CI 62%–87%), whereas the negative predictive value (NPV) was 96% (95% CI 93%–98%). Conclusion. TLE1 is a sensitive and specific marker for synovial sarcoma that can aid in its diagnosis. Due to its involvement in several relevant signaling pathways, TLE1 might have direct relevance to the pathophysiology of the disease.

Background Insufficiency of the rotator cuff is a major problem after resections of proximal humeral tumors and can limit shoulder motion despite preservation of the deltoid muscle and axillary nerve. Allograft-prosthetic composite reconstruction offers one method to reattach the rotator cuff tendons and has been successful in small studies with short followup. However, data are lacking with regard to implant durability, changes in Musculoskeletal Tumor Society (MSTS) scores over time, and delayed complications with extended followup. Questions/purposes (1) What is the cumulative incidence of allograft-prosthetic composite revision surgery 5 years after the procedure? (2) What are the early- and intermediate-term MSTS scores of allograft-prosthetic composite reconstruction of the shoulder? (3) What are the complications of allograft-prosthetic composite reconstruction? Methods Twenty-one patients underwent allograft-prosthetic composite reconstruction after tumor resection of the proximal humerus between 2000 and 2015. Six patients who were lost to followup were not included. All patients had malignant or aggressive benign tumors that could be treated with a wide intraarticular approach preserving the deltoid muscle, axillary nerve, and glenoid. Cumulative incidence of implant revision was calculated with death of the patient as a competing risk. Minimum followup was 24 months (with the exception of one patient who died at 22 months), and median followup was 97 months (range, 20-198 months). The upper extremity MSTS score was used to assess function. Various complications were identified from radiographs and charts. Results The cumulative risk of implant revision was 10.1% at 5 years (95% confidence interval [CI], 1.6%-28.0%). Mean MSTS scores were 86% (± SD 9%) at 1 year and 78% (± SD 13%) at 5 years (mean difference ± SD 9% ± 14%, p = 0.015). Mean active forward elevation was 101° (± SD 33°) at 1 year and 92° (± SD 34°) at 5 years (mean difference ± SD 8° ± 36°, p = 0.41). Notable adverse events included progressive radiographic superior subluxation > 1 cm after 12 months followup (12 of 21 patients), delayed union > 12 months (10 of 21 patients), resorption of the greater tuberosity (nine of 21 patients), and aseptic loosening (three of 21 patients). Conclusions At intermediate 5-year followup, allograft-prosthetic composite reconstruction of the proximal humerus has an acceptable overall MSTS score and a low incidence of implant revision, but loss of patients to followup and exclusion from the study likely make the results seem better than they actually are. The MSTS score deteriorates between 1 and 5 years. Decreased active forward elevation is not likely to be the sole reason for worsening MSTS scores. A variety of delayed complications including delayed union, resorption of the greater tuberosity, and superior subluxation occurs frequently and may contribute to overall scores. Future studies that compare allograft-prosthetic composites against other forms of reconstruction should attempt to control for possible selection bias and have sufficiently long followup to detect the deterioration of MSTS scores that occur with time. Level of Evidence Level IV, therapeutic study.

Mesenchymal chondrosarcoma is a rare but deadly form of chondrosarcoma that typically affects adolescents and young adults. While curative intent is possible for patients with localized disease, few options exist for patients in the unresectable/metastatic setting. Thus, it is imperative to understand the fusion-driven biology of this rare malignant neoplasm so as to lead to the future development of better therapeutics for this disease. This manuscript will briefly review the clinical and pathologic features of mesenchymal chondrosarcoma followed by an appraisal of existing data linked to the fusions, HEY1-NCOA2 and IRF2BP2-CDX1, and the associated downstream pathways.

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BackgroundOne of the major challenges in soft tissue sarcomas is to identify factors that predict metastasis. AZGP1 is a potential biomarker of cancer progression, but its value in soft tissue sarcomas remains unknown. The aim of this study is to determine the expression level of AZGP1 in soft tissue sarcomas, and to analyze its influence on tumor progression.MethodsAZGP1 immunohistochemistry (IHC) and RT-PCR were performed in 86 patients with soft tissue sarcomas. The relationships between AZGP1 levels and clinicopathologic features were analyzed. In vitro experiments were performed using fibrosarcoma (HT1080), rhabdomyosarcoma (RD) and synovial sarcoma (SW982) cell lines to corroborate our findings. We used lentiviral over-expression and knockdown assays to examine how changes of AZGP1 expressions might affect cellular migration and invasion.ResultsThe quantitative RT-PCR results showed that AZGP1 expression was negatively correlated with metastasis and overall survival in soft tissue sarcomas (p < 0.05). Immunohistochemical staining showed lower expression of AZGP1 in patients with metastasis than in those without. Kaplan-Meier survival analysis showed that patients with low expression of AZGP1 had shorter overall (p = 0.056) and metastasis-free survivals (p = 0.038). These findings were corroborated by our in vitro experiments. Over-expression of AZGP1 significantly decreased RD cellular migration and invasion by 64% and 78%, respectively. HT1080 cells migration was inhibited by 2-fold, whereas their invasion was repressed by 7-fold after AZGP1 knockdown.ConclusionsOur study reveals that reduced AZGP1 expression correlates with in vitro cellular migration and invasion. In vivo, it is associated with higher metastatic risk and shorter survival in patients with soft tissue sarcomas.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3962-5) contains supplementary material, which is available to authorized users.