Metachronous Pheochromocytoma and Cholangiocarcinoma in a patient with Neurofibromatosis type 1: a case report

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome caused by mutations in the NF1 gene encoding neurofibromin, leading to an increased risk of benign and malignant tumors, including pheochromocytomas and rare cancers such as cholangiocarcinoma (CCA). We report a novel case of a 45-year-old NF1 patient who underwent adrenalectomy for pheochromocytoma at age 30 and was later diagnosed with CCA during evaluation for chest pain. Imaging revealed hepatic lesions confirmed by biopsy and molecular analysis showing an IDH1 mutation, providing a potential therapeutic target. This metachronous presentation of two rare tumors in an NF1 patient is exceptionally uncommon and has not been previously documented in the literature. The patient was treated with combined chemotherapy and immunotherapy, showing stable disease at three-month follow-up. This case highlights the importance of vigilant long-term surveillance in NF1 patients and the role of molecular profiling in guiding personalized therapeutic strategies.