New Developments in VHL-Associated Neuroendocrine Neoplasms

Curr Oncol Rep. 2025 Jan;27(1):59-67. doi: 10.1007/s11912-024-01631-5. Epub 2025 Jan 5.

Abstract

Purpose of review: The purpose of this review is to outline the current knowledge on epidemiology, diagnosis and management of neuroendocrine neoplasms (NENs) that develop in the context of Von Hippel-Lindau (VHL) syndrome.

Recent findings: Pancreatic NENs develop in 8-17% of VHL patients (vPNENs) and are mostly multi-focal, cystic and non-functioning. Surgical resection is recommended for vPNENS > 3 cm that exhibit higher metastatic potential or in tumors with short doubling time while in the 20% of cases with metastatic disease the HIF-2 A inhibitor belzutifan is considered a promising option. Pheochromocytomas arising in VHL type 2 are often bilateral and have a noradrenergic phenotype while they are associated with increased risk of recurrence. High-specific activity [131I]-MIBG and sunitinib are the treatment options with the highest level of evidence whereas studies on belzutifan are evolving. Life-long surveillance and management in the context of a multidisciplinary team are suggested to achieve the best clinical outcome.

Keywords: Belzutifan; Pancreatic neuroendocrine neoplasms; Pheochromocytoma; VHL.

Publication types

  • Review

MeSH terms

  • Adrenal Gland Neoplasms / therapy
  • Humans
  • Neuroendocrine Tumors* / pathology
  • Neuroendocrine Tumors* / therapy
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Pheochromocytoma / genetics
  • Pheochromocytoma / therapy
  • von Hippel-Lindau Disease* / complications
  • von Hippel-Lindau Disease* / therapy