title: CIC-DUX4 fusion-positive round-cell sarcomas of soft tissue and bone: a single-institution morphological and molecular analysis of seven cases.
abstract: OBJECTIVE
  Round-cell sarcomas lacking specific translocations represent a diagnostic challenge. The aim of this study was to describe seven cases of CIC-DUX4 fusion-positive sarcomas, including the first reported example arising primarily in bone.
  
  
  RESULTS
  Patients ranged in age from 15 years to 44 years (median: 33 years). Six cases arose from the soft tissues, and one from the iliac bone. Morphologically, all cases showed an undifferentiated round-cell population with greater atypia and pleomorphism than Ewing sarcoma. Immunohistochemically, all tumours showed focal and weak positivity for CD99, and five of seven showed nuclear and/or cytoplasmic positivity for Wilms tumour 1. Five patients had lung metastases at presentation. All patients received chemotherapy according to Ewing sarcoma protocols. All but one patient (the one with a bone tumour) died of disease after a mean of 14.5 months from the diagnosis (range: 8-20 months).
  
  
  CONCLUSIONS
  Our series confirms that CIC-DUX4 fusion-positive sarcomas are aggressive tumours with an adverse prognosis, and with clinical, histological and genetic differences from Ewing sarcoma. The best therapeutic approach needs to be investigated.
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gambarotti
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Benini
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.|Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gamberi
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cocchi
authors.affiliation: Department of Oncology, Rizzoli Institute, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
authors.affiliation: Department of Pathology, Treviso Regional Hospital, Treviso, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Sbaraglia
authors.affiliation: Department of Orthopaedic Oncology, Rizzoli Institute, Bologna, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Donati
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vanel
authors.affiliation: Department of Oncology, Rizzoli Institute, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy. alberto.righi@ior.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Righi
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.|Department of Pathology, Treviso Regional Hospital, Treviso, Italy.
authors.forename: Angelo P
authors.initials: AP
authors.lastname: Dei Tos
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018228:Sarcoma, Small Cell / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C574694:CIC-DUX4 fusion protein, human; D015514:Oncogene Proteins, Fusion
keywords: CIC; DUX4; Ewing sarcoma; round-cell sarcoma