BCOR-CCNB3 (Ewing-like) sarcoma: a clinicopathologic analysis of 10 cases, in comparison with conventional Ewing sarcoma

Am J Surg Pathol. 2014 Oct;38(10):1307-18. doi: 10.1097/PAS.0000000000000223.

Abstract

BCOR-CCNB3 fusion transcripts resulting from an X-chromosomal paracentric inversion were recently identified in a series of unclassifiable soft tissue and bone sarcomas with Ewing sarcoma-like morphology. The morphologic and clinical features of these sarcomas are, as yet, not well characterized. Here we describe the clinicopathologic features of 10 cases of BCOR-CCNB3 sarcoma and compare their clinical course with typical Ewing sarcoma. Nine of 10 patients were male, and all were 11 to 18 years of age. Seven tumors were located in the bone and 3 in the deep soft tissues. The histomorphologic spectrum was quite wide, with 7 tumors predominately showing small primitive cell morphology with angulated nuclei simulating so-called atypical Ewing sarcoma and 3 predominately showing spindle cell morphology. Recurrent and metastatic lesions showed increased cellularity and marked pleomorphism. Immunohistochemistry showed expression of CCNB3 (100%), bcl2 (90%), CD99 (60%), and CD117 (60%). Reverse transcription polymerase chain reaction for BCOR-CCNB3 fusion transcripts was positive in all 9 cases, which yielded sufficient extracted RNA. Five- and 10-year survival rates were 75% and 56%, respectively. BCOR-CCNB3 sarcomas located in axial skeleton and soft tissues showed a significantly shorter survival. The Ewing sarcoma overall survival was not statistically different, although there was a trend for longer survival of patients with BCOR-CCNB3 sarcomas in the extremities. In conclusion, this study provides a detailed description of the histologic spectrum, immunohistochemical features, and clinical characteristic of BCOR-CCNB3 sarcoma justifying distinction from Ewing sarcoma with its typical EWS/FUS-ETS translocations. Ideally immunohistochemistry is used in combination with reverse transcription polymerase chain reaction for definitive diagnosis.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Biopsy
  • Bone Neoplasms / chemistry
  • Bone Neoplasms / diagnosis*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Child
  • Cyclin B / analysis*
  • Cyclin B / genetics
  • Gene Fusion
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / analysis*
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Ewing / chemistry
  • Sarcoma, Ewing / diagnosis*
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / mortality
  • Sarcoma, Ewing / secondary
  • Time Factors
  • Translocation, Genetic

Substances

  • BCOR protein, human
  • Biomarkers, Tumor
  • CCNB3 protein, human
  • Cyclin B
  • Proto-Oncogene Proteins
  • Repressor Proteins