Case ReportA Novel CIC-FOXO4 Gene Fusion in Undifferentiated Small Round Cell Sarcoma A Genetically Distinct Variant of Ewing-like SarcomaSugita, Shintaro MD, PhD*; Arai, Yasuhito PhD†; Tonooka, Akiko MD, PhD‡; Hama, Natsuko MS†; Totoki, Yasushi BS†; Fujii, Tomoki MD§; Aoyama, Tomoyuki MT*; Asanuma, Hiroko MT, PhD*; Tsukahara, Tomohide MD, PhD∥; Kaya, Mitsunori MD, PhD¶; Shibata, Tatsuhiro MD, PhD†; Hasegawa, Tadashi MD, PhD*Author Information Departments of *Surgical Pathology ∥Pathology ¶Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo †Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo Departments of ‡Diagnostic Pathology §Hematology and Medical Oncology, Japan Labour Health and Welfare Organization, Kanto Rosai Hospital, Kanagawa, Japan Conflicts of Interest and Source of Funding: Supported by Grants-in-Aid from the Ministry of Health, Labour and Welfare for the 3rd-term Comprehensive 10-year Strategy for Cancer Control and National Cancer Center Research, Development Funds (23-A-8). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. The authors obtained informed consent from the patient for publication. This study was approved by the ethics committee of Sapporo Medical University Hospital, Sapporo, Japan. Correspondence: Tadashi Hasegawa, MD, PhD, Department of Surgical Pathology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan (e-mail: [email protected]). The American Journal of Surgical Pathology: November 2014 - Volume 38 - Issue 11 - p 1571-1576 doi: 10.1097/PAS.0000000000000286 Buy Metrics Abstract Differential diagnosis of small round cell sarcomas (SRCSs) grouped under the Ewing sarcoma family of tumors (ESFT) can be a challenging situation for pathologists. Recent studies have revealed that some groups of Ewing-like sarcoma show typical ESFT morphology but lack any EWSR1-ETS gene fusions. Here we identified a novel gene fusion, CIC-FOXO4, in a case of Ewing-like sarcoma with a t(X;19)(q13;q13.3) translocation. The patient was a 63-year-old man who had an asymptomatic, 30-mm, well-demarcated, intramuscular mass in his right posterior neck, and imaging findings suggested a diagnosis of high-grade sarcoma. He was treated with complete resection and subsequent radiotherapy and chemotherapy. He was alive without local recurrence or distant metastasis 6 months after the operation. Histologic examination revealed SRCS with abundant desmoplastic fibrous stroma suggesting a desmoplastic small round cell tumor. Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively. High-throughput transcriptome sequencing revealed a gene fusion, and the genomic rearrangement between the CIC and FOXO4 genes was identified by fluorescence in situ hybridization. Aside from the desmoplastic stroma, the CIC-FOXO4 fusion sarcoma showed morphologic and immunohistochemical similarity to ESFT and Ewing-like sarcomas, including the recently described CIC-DUX4 fusion sarcoma. Although clinicopathologic analysis with additional cases is necessary, we conclude that CIC-FOXO4 fusion sarcoma is a new type of Ewing-like sarcoma that has a specific genetic signature. These findings have important implications for the differential diagnosis of SRCS. © 2014 by Lippincott Williams & Wilkins.