CIC-DUX4 fusion-positive round-cell sarcomas of soft tissue and bone: a single-institution morphological and molecular analysis of seven cases

Histopathology. 2016 Oct;69(4):624-34. doi: 10.1111/his.12985. Epub 2016 Jun 23.

Abstract

Aims: 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.

Methods and 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.

Keywords: CIC; DUX4; Ewing sarcoma; round-cell sarcoma.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / analysis
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction
  • Sarcoma, Small Cell / genetics*
  • Sarcoma, Small Cell / pathology
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CIC-DUX4 fusion protein, human
  • Oncogene Proteins, Fusion