Journal of endocrinological investigation · 2025
Pediatric and adolescent von Hippel-Lindau disease: tumor profiles, genotype-phenotype correlation and comparison with adults.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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Sharma Anima, Ambulkar Ketki, Karlekar Manjiri, Memon Saba Samad, Patil Virendra, Agarwal Nitish, Sarathi Vijaya, Lila Anurag, Rege Sameer, Malhotra Gaurav, Thakkar Hemangini, Barnabas Rohit, Shah Nalini, Bandgar Tushar
Аннотация
PURPOSE: Data on pediatric/adolescent von Hippel-Lindau (VHL) disease is sparse, and surveillance/management recommendations rely on expert opinions/extrapolations from adults. We aimed to characterize the childhood/adolescent VHL disease phenotype, compare it with adults, and identify genotype-phenotype correlations.
METHODS: Retrospective review of children/adolescents (≤ 19 years) and adults with VHL disease from a single endocrine center (2000-2024). Only neoplasms diagnosed until age 19 years were included in the childhood/adolescent group and compared with the last follow-up of adults.
RESULTS: Twenty-six children/adolescents (median age:15.5 years) were identified. By age 19 years, 81% had pheochromocytoma/paraganglioma (PPGL, of which 10% head-neck), 42% central nervous system hemangioblastoma (CNS-HB), 31% each retinal hemangioblastoma (RHB) and pancreatic neuroendocrine tumor (PNET), and none endolymphatic sac tumor/renal cell carcinoma. At diagnosis, all PPGLs were symptomatic (median size 4.5 cm). CNS-HBs showed female preponderance, with high disease burden (60% symptomatic, 50% synchronous) and surgical requirement by 19 years of age. 2/8 pediatric patients needed surgery for symptomatic PNET before recommended surveillance initiation age (15 years). Two children/adolescents developed polycythemia during follow-up. Compared to adults (n = 39), pediatric/adolescent PPGL patients had significantly higher plasma free-normetanephrine/bilateral/extra-adrenal disease and 8.3-fold higher operative-site recurrence. Neoplasm frequency and other characteristics 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 the largest Asian study describing children/adolescents with VHL disease, we report severe pediatric/adolescent phenotype comparable to adults, need for childhood/adolescent HNPGL, and earlier PNET surveillance, particularly with missense variants.
METHODS: Retrospective review of children/adolescents (≤ 19 years) and adults with VHL disease from a single endocrine center (2000-2024). Only neoplasms diagnosed until age 19 years were included in the childhood/adolescent group and compared with the last follow-up of adults.
RESULTS: Twenty-six children/adolescents (median age:15.5 years) were identified. By age 19 years, 81% had pheochromocytoma/paraganglioma (PPGL, of which 10% head-neck), 42% central nervous system hemangioblastoma (CNS-HB), 31% each retinal hemangioblastoma (RHB) and pancreatic neuroendocrine tumor (PNET), and none endolymphatic sac tumor/renal cell carcinoma. At diagnosis, all PPGLs were symptomatic (median size 4.5 cm). CNS-HBs showed female preponderance, with high disease burden (60% symptomatic, 50% synchronous) and surgical requirement by 19 years of age. 2/8 pediatric patients needed surgery for symptomatic PNET before recommended surveillance initiation age (15 years). Two children/adolescents developed polycythemia during follow-up. Compared to adults (n = 39), pediatric/adolescent PPGL patients had significantly higher plasma free-normetanephrine/bilateral/extra-adrenal disease and 8.3-fold higher operative-site recurrence. Neoplasm frequency and other characteristics 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 the largest Asian study describing children/adolescents with VHL disease, we report severe pediatric/adolescent phenotype comparable to adults, need for childhood/adolescent HNPGL, and earlier PNET surveillance, particularly with missense variants.