Von Hippel–Lindau Disease-Associated Endolymphatic Sac Tumours: Seven Cases and Genotype–Phenotype Features

TL;DR

This study examines seven cases of rare Von Hippel–Lindau disease-related tumors, highlighting early symptoms, surgical treatments, and genetic patterns to improve diagnosis and care.

Contribution

The study identifies genotype–phenotype correlations and treatment outcomes in a rare tumor type associated with Von Hippel–Lindau disease.

Findings

All seven patients presented with hearing loss and most had facial nerve paralysis at a young age.

Surgical removal with nerve grafting improved facial nerve function in some patients.

VHL gene mutations in specific exons correlated with distinct clinical features like tumor location and progression during pregnancy.

Abstract

Von Hippel–Lindau disease-associated endolymphatic sac tumors are challenging to diagnose due to their rarity and nonspecific symptoms. This study of seven patients found that all experienced hearing loss, often with facial nerve paralysis that began at a young age. Surgical removal was the primary treatment, with postoperative facial nerve function improving through procedures like nerve grafting. Genetic testing revealed that mutations in different parts of the Von Hippel–Lindau gene were linked to clinical features. Notably, two female patients experienced disease progression during pregnancy. This study concludes that optimal patient outcomes rely on surgical management, genetic diagnosis, and collaborative multidisciplinary care.

Von Hippel–Lindau disease-associated endolymphatic sac tumors (VHL-associated ELSTs) present diagnostic challenges due to their rarity and nonspecific symptoms. This study describes clinical, pathological and genotypic features to guide treatment. We retrospectively analyzed seven patients with VHL-associated ELSTs. The mean age of otologic symptom [hearing loss (100%) and facial nerve paralysis (85.71%)] onset was 22.43 ± 8.68 years (range: 10–33). Surgical management included trans-labyrinthine and subtotal temporal bone resection approaches. Among three patients with severe preoperative facial nerve dysfunction, two underwent great auricular nerve grafting improved to House–Brackmann grade IV, while one receiving hypoglossal–facial nerve anastomosis reached grade V. Genetic testing identified pathogenic VHL gene missense mutations in three patients. Two female patients demonstrated disease progression during pregnancy. Literature analysis revealed exon-specific patterns: Exon 1 mutations correlated with cerebellar/spinal hemangioblastomas in female patients, while Exon 3 mutations were associated with multisystem tumors. These findings support that VHL-associated ELSTs manifest early with otologic symptoms and demonstrate exon-specific phenotypic patterns. Optimal management requires complete surgical resection, genetic diagnosis, and a multidisciplinary approach to address these complex tumors and achieve favorable outcomes.

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