Case ReportsA “Double-Hit” Translocation Sarcoma—First Report of the Co-occurrence of EWSR1-FLI1 and MTMR2-NTRK2 Fusion in a Small Round Blue Cell SarcomaVargas, Ana Cristina PhD, FRCPA*,†,‡; Kurek, Caroline MBBS*; Bonar, Fiona FRCPA*; Maclean, Fiona FRCPA*,†,§; Qiu, Min Ru PhD, FRCPA∥; Boyle, Richard FRACS, FA‡,¶; Brookwell, Ross PhD**; Gill, Anthony J. FRCPA†,‡,††Author Information From the *Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park †Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards ‡University of Sydney, Sydney §Faculty of Medicine and Health Sciences Macquarie University, North Ryde ∥Sydpath, St Vincent's Hospital ¶Chris O'Brien Lifehouse, Sydney, New South Wales **Department of Cytogenetics, Sullivan Nicolaides Pathology, Brisbane, Queensland ††NSW Health Pathology, Department of Anatomical Pathology Royal North, Shore Hospital, St Leonards, New South Wales, Australia. Reprints: Ana Cristina Vargas, PhD, FRCPA, Douglass Hanly Moir Pathology, 14 Giffnock Ave, Macquarie Park, New South Wales 2113, Australia. E-mail: email@example.com. Support was received from the Hanna's Chance Foundation through the Australia and New Zealand Sarcoma Association. The authors have no conflicts to declare. AJSP: Reviews & Reports: March/April 2020 - Volume 25 - Issue 2 - p 97-100 doi: 10.1097/PCR.0000000000000369 Buy Metrics Abstract We report a case of a 51-year-old man with primary diagnosis of Ewing sarcoma confined to the soft tissue, associated with EWSR1-FLI1 gene fusion demonstrated by fluorescence in situ hybridization (FISH). Six years after the diagnosis, immunohistochemistry for NTRK (neurotrophic receptor tyrosine kinase 1–3) was performed on this tumor using 2 Pan-Trk rabbit monoclonal antibodies, A7H6R (Cell Signaling Technology, Danvers, Mass) and EPR17341 (Abcam, Cambridge, Mass). Both clones showed diffuse moderate to strong cytoplasmic expression including presence of nuclear stain. RNA sequencing demonstrated the co-occurrence of MTMR2-NTRK2, a novel gene fusion, in the same tumor block used for EWSR1 FISH testing. While FISH for NRK2 did not confirm gene rearrangement, an atypical signal pattern was identified. This case challenges the concept that NTRK fusions are mutually exclusive with other oncogenic drivers. The clinical course of this patient has also been unusual as the tumor has followed an indolent course with no evidence of recurrent or metastatic disease. © 2020 Lippincott Williams & Wilkins, Inc.