title: Ewing-like sarcoma with CIC-DUX4 gene fusion in a patient with neurofibromatosis type 1. A hitherto unreported association.
abstract: Sarcoma with CIC-DUX4 gene fusion is emerging as the most prevalent subset of Ewing-like undifferentiated small round cell sarcomas with around 50 cases published. We report hereby the case of a 40-year-old male who presented a CIC-DUX4 sarcoma in deep soft tissues in his thigh. He had been diagnosed with neurofibromatosis type 1 at age 19 and over the years underwent resection of multiple neural neoplasms, including two malignant peripheral nerve sheath tumors with classical spindle-cell histopathology. The CIC-DUX4 sarcoma was treated with surgical resection, radiation and chemotherapy, but lung and brain metastases developed and the patient died from the disease 14 months after diagnosis. This is the first case of sarcoma with CIC-DUX4 gene fusion reported in a patient with NF1. Whether this association is coincidental or CIC-DUX4 sarcomas could be related to NF1 remains to be clarified. Study of alternative molecular alterations in EWSR1-negative undifferentiated small round cell sarcomas is clinically relevant, since CIC-DUX4 sarcomas seem to be a very aggressive subset with poor response to the presently used therapeutic regimens.
authors.affiliation: Department of Pathology, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain. Electronic address: jtardio.hflr@salud.madrid.org.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Tardío
authors.affiliation: Department of Pathology, Instituto Valenciano de Oncología, 46009 Valencia, Spain. Electronic address: isidro.machado@uv.es.
authors.forename: Isidro
authors.initials: I
authors.lastname: Machado
authors.affiliation: Department of Pathology, Molecular Biology Section, Universidad de Valencia, 46010 Valencia, Spain. Electronic address: lara.navarro@uv.es.
authors.forename: Lara
authors.initials: L
authors.lastname: Navarro
authors.affiliation: Department of Pathology, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain. Electronic address: franklineduardo.idrovo@salud.madrid.org.
authors.forename: Franklin
authors.initials: F
authors.lastname: Idrovo
authors.affiliation: Department of Pathology. Hospital Clínico San Carlos, 28040 Madrid, Spain. Electronic address: jsanzo@salud.madrid.org.
authors.forename: Julián
authors.initials: J
authors.lastname: Sanz-Ortega
authors.affiliation: Department of Pathology, Molecular Biology Section, Universidad de Valencia, 46010 Valencia, Spain. Electronic address: antonio.pellin@uv.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellín
authors.affiliation: Department of Pathology, Universidad de Valencia, 46010 Valencia, Spain. Electronic address: antonio.llombart@uv.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000556:secondary; D017809:Fatal Outcome; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D009456:Neurofibromatosis 1 / Q000150:complications*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D018228:Sarcoma, Small Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: C574694:CIC-DUX4 fusion protein, human; D015514:Oncogene Proteins, Fusion
keywords: Ewing-like sarcoma; Neurofibromatosis type 1; Reverse transcription polymerase chain reaction; Sarcoma with CIC-DUX4 gene fusion; Undifferentiated small round cell sarcoma