EZR-ROS1 fusion renal cell carcinoma mimicking urothelial carcinoma: report of a previously undescribed gene fusion in renal cell carcinoma

Virchows Arch. 2022 Feb;480(2):487-492. doi: 10.1007/s00428-021-03138-x. Epub 2021 Jun 14.

Abstract

A subset of renal cell carcinomas harbor gene fusions, and we report the first case of an EZR-ROS1 fusion in renal cell carcinoma. A 47-year-old female presented with hematuria and a mass involving the renal pelvis. Renal biopsy revealed a tumor with solid and tubular architecture that was diffusely positive for PAX8, CK7, and vimentin; retained expression of INI1; focally positive for P504S; and negative for GATA3 and TFE3. Partial nephrectomy was performed, and histologically, the tumor had solid and tubular architecture with mucin-like content within tubules. The nuclei corresponded to WHO/ISUP grade 2 and 3. The morphology was neither specific nor diagnostic, and a final diagnosis of unclassified renal cell carcinoma with solid and tubular architecture was rendered. Molecular sequencing revealed an EZR-ROS1 fusion: a fusion that has never been reported in renal cell carcinoma. Recognition of this fusion is of significance if the tumor becomes metastatic as treatment with crizotinib may be considered.

Keywords: DNA sequencing; EZR-ROS1 fusion; Kidney; RNA sequencing; Renal mass.

Publication types

  • Case Reports

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell* / diagnosis
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Transitional Cell*
  • Female
  • Gene Fusion
  • Humans
  • Kidney Neoplasms* / diagnosis
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / metabolism
  • Middle Aged
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Urinary Bladder Neoplasms*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human