Expanding the clinical tumor phenotype of the EPAS1-associated tumor syndrome.

EPAS1 somatic mosaic variants: pancreatic neuroendocrine tumors via the VHL-HIF2α axis

Pacak-Zhuang syndrome (PZS), defined by the triad of pheochromocytoma/paraganglioma, ampullary somatostatinoma, and erythrocytosis, is expanded to a new manifestation: pancreatic neuroendocrine tumors (P-NETs). Two institutions report PZS patients with P-NETs associated with somatic mosaic EPAS1/HIF2α variants, establishing a link with von Hippel-Lindau disease (VHL) via HIF-2α regulation. This case extends understanding of hypoxic oncogenesis and HIF-2α's role in pancreatic tumor development.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Expansion of Pacak-Zhuang syndrome to pancreatic NETs is clinically important for teams managing these patients: pancreatic surveillance should be integrated into follow-up. The mechanistic VHL-HIF2α-NET-P link is biologically consistent and reinforces the need for a multi-organ approach in this rare syndrome.

Clinical impact: 2/3 · Evidence quality: 1/3 · Novelty: 2/2 · Sample size: 0/1 · Journal quality: 1/1 → Total: 6/10