EPAS1-related pheochromocytoma/paraganglioma

Endocr Relat Cancer. 2024 Jun 10;31(8):e230303. doi: 10.1530/ERC-23-0303. Print 2024 Aug 1.

Abstract

In 2012, somatic EPAS1 pathogenic variants were found to cause a triad of pheochromocytoma/paragangliomas (PPGLs), polycythemia, and somatostatinoma. Since then, a limited number of studies on this subject have been reported, and data on the long-term outcome of metastatic disease are not available on this rare syndrome. We comprehensively reviewed EPAS1-related PPGL and describe an unusual patient who has been living with an EPAS1-related metastatic PPGL for 47 years. The results of this work show that EPAS1 pathogenic variants are rare, more in females and patients without pathogenic variants in other PPGL susceptibility genes. PPGLs are the most common manifestation followed by polycythemia and somatostatinoma. The EPAS1 pathogenic variants are often postzygotic, and the timing of their acquirement during embryonic development seems to correlate with the number and timing of development of the disease manifestations. Although recurrent and multifocal disease is common in EPAS1-related PPGL, distant metastases are uncommon and usually indolent. This is illustrated by a case of a man who was diagnosed at the age of 9 years and is currently 56 years old, alive, and well for 47 years with these metastases. He was found to have a somatic EPAS1 pathogenic variant (c.1592C>A, p.Pro531His) in bilateral pheochomocytoma and a pancreatic NET (somatostatinoma) but not in genomic DNA isolated from peripheral leukocytes. This and previous reports suggest that distant metastases are uncommon and less aggressive in EPAS1-related PPGLs compared to those found in other hereditary PPGLs.

Keywords: EPAS1; EPAS1 mutations; HIF-2α; paraganglioma; pheochromocytoma.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adrenal Gland Neoplasms* / genetics
  • Adrenal Gland Neoplasms* / pathology
  • Basic Helix-Loop-Helix Transcription Factors* / genetics
  • Humans
  • Male
  • Middle Aged
  • Paraganglioma* / genetics
  • Paraganglioma* / pathology
  • Pheochromocytoma* / genetics
  • Pheochromocytoma* / pathology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • endothelial PAS domain-containing protein 1