RBM10-TFE3 renal cell carcinoma. A Potential diagnostic pitfall due to cryptic intrachromosomal Xp11.2 inversion resulting in false-negative TFE3 FISH

Pedram Argani, Lei Zhang, Victor E. Reuter, Satish K. Tickoo, Cristina R. Antonescu

Research output: Contribution to journalArticlepeer-review

Abstract

Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-Apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion. TFE3 rearrangement was not detected by conventional TFE3 break-Apart FISH, but was suggested by strong diffuse TFE3 immunoreactivity in a clean background. We then developed novel fosmid probes to detect the RBM10-TFE3 gene fusion in archival material. These cases validate RBM10-TFE3 as a recurrent gene fusion in Xp11 translocation RCC, illustrate a source of false-negative TFE3 break-Apart FISH, and highlight the complementary role of TFE3 IHC and TFE3 FISH.

Original languageEnglish (US)
Pages (from-to)655-662
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume41
Issue number5
DOIs
StatePublished - 2017

Keywords

  • Renal neoplasm
  • TFE3
  • Translocation

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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