P3.CR-07 Comprehensive Genomic Profiles for a Mediastinal Tumor Suspected of Synovial Sarcoma: A Case Report

Abstract

Synovial sarcoma (SS) is an aggressive malignant tumor and accounts for 5 to 10% of all types of soft tissue sarcomas. SS commonly occurs in the deep tissue adjacent to the joints or tendons in the limbs while SS rarely occurs in the mediastinum. Most of SS harbor t(X;18)(p11.2;q11.2), which leads to chimeric fusion of SYT with one of the SSX genes. Furthermore, somatic mutations of cancer-related genes such as PIKC3A, TERT, CDH1, and PTEN have also been reported in the SS even though the frequencies of these genetic alterations were not high. Recently, the comprehensive genomic profile (CGP) using the next-generation sequencing (NGS) is widely used for better understanding of tumorigenesis and it can also provide clinically actionable information to guide treatment decisions for patients. In this study, the clinical and histological records of an anterior mediastinal tumor suspected of SS were reviewed, and a reverse transcript polymerase chain reaction (RT-PCR) assay and NGS using a high sensitivity amplicon-based targeted sequencing method incorporating molecular barcodes (a panel designed for hotspots of 47 cancer-related genes) were performed to identify the genetic alterations. A 78 years old woman was referred to our hospital because of approximately 9 cm anterior mediastinal tumor. A positron emission tomography showed the high fluorine-18-fluorodeoxyglucose uptake. The patient underwent median sternotomy and resection of the tumor combined with wedge resection of the left upper lobe of lung. Histological examination revealed a monomorphic spindle cell growth and immunohistochemical stains (AE1/AE3, CAM5.2, CD34, CD99, Desmin, Nestin, a-SMA, CDK4, CD56, c-kit, EMA, and S-100) were negative, so the tumor was suspected of SS. We performed a RT-PCR assay for SYT-SXX fusion, however, it was not detected. NGS analysis revealed the presence of hotspot mutations in 4 cancer-related genes (PIK3CA, CDKN2A, PTEN, and MAP2K4). Because the tumor was completely resected, an adjuvant therapy had not been planned and the scheduled medical checkup has been performed. Fortunately, the patient is alive without any recurrence for 5 years. The genetic features of a mediastinal tumor suspected of SS, without SYT-SSX fusion, were evaluated by CGP analysis. In case of the rare tumor especially when it occurs in the unusual location and the histological and molecular assessments are not conclusive, a CGP assay may be helpful to reveal the genetic feature of the tumor and to determine the effective targeted drugs.