NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma

Hum Pathol. 2017 Jul:65:225-230. doi: 10.1016/j.humpath.2017.01.012. Epub 2017 Feb 8.


CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion.

Keywords: CIC; CIC-rearranged sarcoma; Fluorescence in situ hybridization; Immunohistochemistry; NUTM2A; NUTM2A-CIC fusion sarcoma; Next-generation sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Cell Proliferation
  • Disease Progression
  • Exons
  • Fatal Outcome
  • Female
  • Gene Fusion*
  • Gene Rearrangement*
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Nuclear Proteins
  • Oncogene Proteins, Fusion / genetics*
  • Phenotype
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma / chemistry
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Transcription Factors
  • Tumor Burden


  • Biomarkers, Tumor
  • CIC protein, human
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • NKX2-2 protein, human
  • NUTM2A-CIC fusion protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Repressor Proteins
  • Transcription Factors