Rheb/mTOR/p70s6k Cascade and TFE3 Expression in Conventional and Sclerosing PEComas of the Urinary Tract

Appl Immunohistochem Mol Morphol. 2016 Aug;24(7):514-20. doi: 10.1097/PAI.0000000000000209.

Abstract

Perivascular epithelioid cell tumors (PEComas) are rarely found in the urinary tract. The clinicopathologic characteristics of 10 cases, retrospectively collected from 5 medical institutions in 3 different European countries, are presented in this study. Male/female ratio was 3:7 and the average age at diagnosis was 62.7 years. Nine cases were sporadic and 1 showed germline mutation of the TSC2 gene. Eight cases were located in the kidney, 1 in the left adrenal and 1 in the right ureter. All of the patients were alive and free of disease at the time of last contact (mean follow-up, 14.1 mo). Four cases displayed a conventional morphology and 6 showed a prominent sclerotic stroma. By immunohistochemistry, melanocytic markers were consistently expressed, especially HMB-45 (10 cases), MiTF (9 cases), and Melan-A (6 cases). Desmin was expressed in 6 cases; 2 cases were positive for CD117; a single case showed TFE3 expression. pMAPK, mTOR, and pAKT demonstrated variable immunostaining with focal positivity in 7, 4, and 2 cases, respectively. Cytokeratins were repeatedly negative in all cases. PEComas in the urinary tract, especially in the renal region, may show a relatively high frequency of the sclerosing histologic subtype. Knowledge of the distinct histology and immunohistochemical profile is vital to correctly diagnose this rare entity.

MeSH terms

  • Adult
  • Aged
  • Angiomyolipoma / genetics
  • Angiomyolipoma / physiopathology
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Female
  • Histiocytoma, Benign Fibrous / genetics
  • Histiocytoma, Benign Fibrous / physiopathology*
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / physiopathology
  • Male
  • Middle Aged
  • Perivascular Epithelioid Cell Neoplasms / genetics
  • Perivascular Epithelioid Cell Neoplasms / physiopathology*
  • Retrospective Studies
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / physiopathology
  • Urinary Tract / physiopathology
  • Urologic Neoplasms / genetics
  • Urologic Neoplasms / physiopathology*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFE3 protein, human
  • Interferon-gamma
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases

Supplementary concepts

  • Tsc2 Angiomyolipomas, Renal, Modifier Of