Malignant perivascular epithelioid cell neoplasm (PEComa) of the urinary bladder with TFE3 gene rearrangement: clinicopathologic, immunohistochemical, and molecular features

Am J Surg Pathol. 2013 Oct;37(10):1619-26. doi: 10.1097/PAS.0b013e318293729d.

Abstract

Recently, a small subgroup of PEComas has been recognized to harbor rearrangements involving TFE3, a gene also involved in rearrangements in translocation-associated renal cell carcinomas and alveolar soft part sarcomas. The few TFE3 rearrangement-associated PEComas reported have exhibited distinctive pathologic characteristics contrasting to PEComas in general, including predominantly epithelioid nested or alveolar morphology and underexpression of muscle markers by immunohistochemistry. In this study, we report the clinicopathologic, immunohistochemical, and molecular features of a primary urinary bladder PEComa diagnosed by transurethral resection in a 55-year-old woman that clinically mimicked urothelial carcinoma. Light microscopy demonstrated mixed spindle cell and epithelioid morphology with the epithelioid component preferentially associated with blood vessels. Immunohistochemistry revealed positive staining for HMB45, tyrosinase, MiTF, cathepsin K, smooth muscle actin, and TFE3 protein. Fluorescence in situ hybridization for the TFE3 gene revealed a split signal pattern, indicating TFE3 rearrangement. X chromosome inactivation analysis demonstrated a clonal pattern despite the heterogenous appearance of the tumor. Unfortunately, despite surgical resection and sarcoma-directed therapy, the patient died of metastatic disease 12 months after diagnosis. This report adds to the known data regarding urinary bladder PEComas and PEComas with TFE3 rearrangement, indicating that both can pursue an aggressive course. Although the few reported TFE3-rearranged PEComas have predominantly lacked a spindle cell component and expression of smooth muscle actin and MiTF by immunohistochemistry, the findings in this study indicate that these features are sometimes present in TFE3-rearranged PEComas.

Publication types

  • Case Reports

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Fatal Outcome
  • Female
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Perivascular Epithelioid Cell Neoplasms / genetics*
  • Perivascular Epithelioid Cell Neoplasms / metabolism
  • Perivascular Epithelioid Cell Neoplasms / pathology*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFE3 protein, human