Original ArticlesSRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular TumorsKaranian, Marie MD*,†; Kelsey, Anna MD‡; Paindavoine, Sandrine MSc*; Duc, Adeline MSc†; Vanacker, Helene MD§; Hook, Liz MD, PhD, FCRPath∥; Weinbreck, Nicolas MD¶; Delfour, Christophe MD#; Minard, Veronique MD, PhD**; Baillard, Pauline MD††; Blay, Jean-Yves MD, PhD†,§; Pissaloux, Daniel PhD*,†; Tirode, Franck PhD†Author Information Departments of *Biopathology §Oncology, Centre Leon Berard †Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Cancer Research of Lyon, Centre Leon Berard ††Department of Pathology, Hospital University, Lyon ¶Medipath Pathology Laboratory, Frejus #Department of Pathology, Hospital University, Montpellier **Department of Pediatric Oncology, Institute Gustave Roussy, Villejuif, France ‡Department of Pediatric Histopathology, Manchester University NHS Foundation Trust, Royal Manchester Children Hospital, Manchester ∥Department of Pathology, University of Cambridge, Cambridge, UK Conflicts of Interest and Source of Funding: Supported by the Institut National du Cancer and the French Health Ministry (Direction Générale de l’Offre de Soins), grant INCa-DGOS_13219 (iMAPS project) and by the SIRIC LYriCAN (INCa-DGOS-Inserm_12563). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this study. Correspondence: Marie Karanian, MD, Pathology Department, Centre Leon Berard, 28 Rue Laënnec, 69373 Lyon Cedex 08, France (e-mail: [email protected]). The American Journal of Surgical Pathology: December 2020 - Volume 44 - Issue 12 - p 1725-1735 doi: 10.1097/PAS.0000000000001546 Buy SDC Metrics Abstract Pericytic tumors encompass several entities sharing morphologic and immunohistochemical features. A subset of perivascular myoid tumors associated with the SRF-RELA fusion gene was previously described. Herein, we report a series of 13 tumors belonging to this group, in which we have identified new fusion genes by RNA-sequencing, thus expanding the molecular spectrum of this entity. All patients except 1 were children and infants. The tumors, frequently located in the head (n=8), had a mean size of 38 mm (range 10 to 150 mm) and were mostly (n=9) well-circumscribed. Exploration of the follow-up data (ranging from 3 to 68 mo) confirmed the benign behavior of these tumors. These neoplasms presented a spectrum of morphologies, ranging from perivascular patterns to myoid appearance. Tumor cells presented mitotic figures but without marked atypia. Some of these tumors could mimic sarcoma. The immunohistochemical profiles confirmed a pericytic differentiation with the expression of the smooth muscle actin and the h-caldesmon, as well as the frequent positivity for pan-cytokeratin. The molecular analysis identified the expected SRF-RELA fusion gene, in addition to other genetic alterations, all involving SRF fused to CITED1, CITED2, NFKBIE, or NCOA2. The detection of SRF-NCOA2 fusions in spindle cell rhabdomyosarcoma of the infant has previously been described, representing a risk of misdiagnosis, although the cases reported herein did not express MyoD1. Finally, clustering analyses confirmed that this group of SRF-fused perivascular myoid tumors forms a distinct entity, different from other perivascular tumors, spindle cell rhabdomyosarcomas of the infant, and smooth muscle tumors. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.