OR28-08 Pediatric and Adolescent von-Hippel Lindau Disease: Tumor Profiles, Genotype-Phenotype Correlations, and Comparison with Adults

Abstract Disclosure: A. Sharma: None. K. Ambulkar: None. M. Karlekar: None. S. Memon: None. V. Patil: None. N. Agarwal: None. V. Sarathi: None. A. Lila: None. S. Rege: None. H. Thakkar: None. G. Malhotra: None. R. Barnabas: None. N. Shah: None. T. Bandgar: None. Background: Data on pediatric/adolescent von Hippel-Lindau (VHL) disease is sparse, and comprehensive studies detailing the phenotype of all the associated neoplasms are lacking. Their current surveillance and management rely on expert opinion/extrapolation from adults, not individualized to the mutation type.Objective: To characterize the childhood/adolescent-onset VHL disease phenotype, compare it to adult-onset disease, and identify genotype-phenotype correlations.Methods: This was a retrospective review of children/adolescents (≤19 years) and adults (≥20 years) with a clinical (15%) or genetic (85%: 66% missense, and 19% truncating variants) diagnosis of VHL disease from a single endocrine center (2000-2024). Only neoplasms diagnosed until 19 years of age were included in the childhood/adolescent group and compared with the last follow-up of adults. The demographic, clinical data, genetics, anatomical/functional imaging, operative details, and histopathology (in operated patients) were noted for each VHL-associated neoplasm.Results: In 26 children/adolescents, by age 19 years, 81% (21/26) developed pheochromocytoma/paraganglioma (PPGL, of which 10% head and neck), 42% (10/24) central nervous system hemangioblastoma (CNS-HB), 31% each retinal RHB (5/16) and pancreatic neuroendocrine tumor (PNET, 8/26), and none endolymphatic sac tumor/renal cell carcinoma. At diagnosis, all those with PPGLs were symptomatic (median size 4.5 cm, 52 lesions). CNS-HBs showed female preponderance, a high disease burden (60% symptomatic, 50% synchronous in ≥2/3 components of the neuroaxis), and surgical requirement by age 19. Two pediatric patients needed surgery for a symptomatic PNET before the recommended surveillance initiation age (15 years). Two developed polycythemia on follow-up. Compared to adults (n=39), pediatric/adolescent PPGL patients had significantly higher baseline plasma free-normetanephrine (median 1099 vs. 2513 pg/mL), more bilateral (47% vs. 76%) and extra-adrenal (19% vs. 48%) disease by 19 years, and 8.3-fold higher operative-site recurrence over a similar follow-up duration (median 108 months in adults vs. 75 months in children/adolescents) independent of cortical-sparing surgery. CNS/RHB and PNET frequency and burden by 19 years resembled adults. Childhood/adolescent PPGLs occurred predominantly (16/17) and PNETs exclusively, with missense variants. Codon 167 missense variants were associated with synchronous bilateral pheochromocytomas.Conclusion: In pediatric/adolescent VHL disease, we report a severe phenotype, more extensive (PPGL) or comparable to adults, and the need for head and neck PGL and earlier PNET surveillance. The occurrence of PPGLs and PNETs almost exclusively in children and adolescents with missense VHL variants suggests the genotype may guide the pediatric surveillance strategy for these neoplasms. Presentation: Monday, July 14, 2025