Title : Isolated adrenal pheochromocytoma in a 9-year-lld boy with von hippel-lindau type 2C (V84M) mutation presenting with papilledema and hyperpigmented macules: A case report
Abstract:
Background: Pediatric pheochromocytoma is rare, often syndromic, and may present atypically. We describe a 9-year-old boy diagnosed with adrenal pheochromocytoma associated with a pathogenic VHL gene variant, presenting with sustained hypertension and papilledema.
Case Presentation: A previously healthy 9-year-old boy presented with abdominal pain, vomiting, and persistent hypertension. Physical exam revealed tachycardia, papilledema (Grade 4), and multiple oval greyish-brown hyperpigmented macules over the trunk and limbs. 24-hour urinary Vanillylmandelic acid (VMA) levels and Plasma metanephrines were elevated. Imaging (CECT and PET CT) revealed two necrotic, metabolically active lesions in the right adrenal region. The patient underwent cortical?sparing right adrenalectomy, which revealed a 6×4×2 cm well?circumscribed, encapsulated mass with focal necrosis and mild capsular infiltration.
Histology displayed classic zellballen architecture, confirming pheochromocytoma.
Genetics: Whole-exome sequencing of the patient identified a heterozygous, pathogenic mutation involving c.250G>A, Exon 1, on the VHL gene, consistent with an Autosomal Dominant pattern. No other family members tested positive for the mutation, indicating a de novo event.
Genetic counselling and family education were provided.
Discussion: Pediatric pheochromocytoma is highly associated with hereditary syndromes (~66% by some estimates). VHL syndrome type 2C presents primarily with pheochromocytoma and minimal risk for RCC or CNS hemangioblastomas; it is often linked to missense mutations that preserve HIF1 regulation. The V84M mutation, reported in pediatric isolated pheochromocytoma, supports a genotype-phenotype correlation. The patient's sustained hypertension, vomiting, and unusually severe papilledema reflect chronic catecholamine excess and elevated intracranial pressure.
Management and Outcome: After surgical resection, blood pressure and catecholamine metabolites normalized. The patient remains normotensive with no biochemical or radiologic recurrence at 18-month follow-up. Lifelong surveillance with annual biochemical tests and biennial imaging is planned due to the risk of multifocal syndrome-related tumors.
Conclusion: This case emphasizes the need for genetic evaluation in pediatric pheochromocytoma, even when familial history is negative. Early identification of VHL?type 2C enables tailored surveillance and family counseling.
