Original ArticlesClinicopathologic Features of a Series of Primary Renal CIC-rearranged Sarcomas With Comprehensive Molecular AnalysisMangray, Shamlal MB, BS*; Kelly, David R. MD†; LeGuellec, Sophie MD‡; Fridman, Eddie MD§; Aggarwal, Sangeeta MD∥; Shago, Mary PhD¶; Matoso, Andres MD#; Madison, Russell BA**; Pramanik, Sharmila MB, BS∥; Zhong, Shan PhD**; Li, Rong MD, PhD†; Lombardo, Kara A. BS*; Cramer, Stuart MD†; Pressey, Joseph MD††; Ross, Jeffrey S. MD**,‡‡; Corona, Robert J. DO‡‡; Bratslavsky, Gennady MD‡‡; Argani, Pedram MD#; Coindre, Jean-Michel MD§§; Somers, Gino R. MB, BS, BScMed, PhD, FRCPA¶; Ali, Siraj M. MD, PhD**; Yakirevich, Evgeny MD, DSc*Author Information *Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI †Children’s of Alabama & University of Alabama Medical School, Birmingham, AL ‡Claudius Regaud Institute, IUCT-Oncopole, Toulouse §§Bergonie Institute, Bordeaux, France §Sheba Medical Center, Tel Aviv, Israel ∥Santa Clara Valley Medical Center, San Jose, CA ¶The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada #Johns Hopkins University School of Medicine, Baltimore, MD **Foundation Medicine Inc., Cambridge, MA ††Children’s Hospital of Cincinnati, Cincinnati, OH ‡‡Upstate Medical University, Syracuse, NY Conflicts of Interest and Source of Funding: J.S.R., R.M., S.Z., and S.M.A. have equity interests in Foundation Medicine Inc. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Evgeny Yakirevich, MD, DSc, Rhode Island Hospital, APC 12, 593 Eddy Street, Providence, RI 02903 (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: October 2018 - Volume 42 - Issue 10 - p 1360-1369 doi: 10.1097/PAS.0000000000001098 Buy SDC Metrics Abstract CIC-rearranged sarcomas rarely occur in visceral organs including the kidney. The most common fusion partner with CIC is the DUX4 gene, but variant fusion partners have also been reported. Herein, we describe the clinicopathologic features and comprehensive molecular profiling of 4 cases of primary renal CIC-rearranged sarcomas. All cases occurred in females, age range 13 to 82 years and included 3 resections and 1 needle biopsy specimen. There was a tendency for development of metastatic disease predominantly to the lungs and poor disease outcome despite different treatment strategies. Histologically, variable round cell (20% to 100%), spindle cell (0% to 80%), and rhabdoid morphologies (0% to 20%) were seen. By immunohistochemistry diffuse WT1 nuclear (2 to 3+, ∼90%) labeling was present in 1 case, with cytoplasmic staining in the others (3+, 40% to 75%). CD99 was focally positive in all 4 cases (≤10%); 1 case each was diffusely positive for c-myc (2 to 3+, ∼90%) and ETV4 (3+, ∼90%); 1 case was focally positive for c-myc (2+, ∼5%) and calretinin (2+, ∼5%); and all cases were negative for cytokeratin and NKX2.2. CIC rearrangement by fluorescence in situ hybridization was present in the 3 cases tested. Comprehensive genomic profiling (CGP) of 3 cases revealed a CIC-DUX4 fusion in 2 cases, and 1 CIC-NUTM1 fusion. All 4 CIC-rearranged renal sarcomas had low mutation burden, and except HLA-A and MLL mutations lacked genomic alterations in other oncogenic drivers. Material from the needle biopsy was insufficient for CGP but that case was positive with the DUX4 immunohistochemical stain as were the 2 CIC-DUX4 tumors. In conclusion, CIC-rearranged sarcomas rarely occur in the kidney with a tendency for poor outcome and in this series we illustrate an example with CIC-NUTM1 fusion, an emerging variant, at a visceral site. Testing by fluorescence in situ hybridization or CGP is optimal to avoid missing cases that harbor variant fusion partners. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.