Prevalence of Endocrine Manifestations and GIST in 108 Systematically Screened Patients With Neurofibromatosis Type 1.

Context: In patients with neurofibromatosis type 1 (NF1), guidelines suggest screening for pheochromocytoma by metanephrine measurement and abdominal imaging, which may lead to the discovery of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and their differential diagnosis, gastrointestinal stromal tumors (GISTs). Other endocrine manifestations such as follicular thyroid carcinoma and primary hyperparathyroidism have also been reported in a few cases. Objective: This study aimed to describe prevalence and clinical presentation of these manifestations through systematic screening in a large cohort of patients. Methods: In this monocentric retrospective study, 108 patients with NF1 were included and screened for endocrine manifestations and GISTs. Clinical, laboratory, molecular profile, pathology, and morphologic (abdominal computed tomography scan and/or magnetic resonance imaging) and functional imaging were collected. Results: Twenty-four patients (22.2% of the cohort, 16 female, mean age 42.6 years) presented with pheochromocytomas that were unilateral in 65.5%, benign in 89.7%, and with a ganglioneural component in 20.7%. Three female patients (2.8% of the cohort, aged 42-63 years) presented with well-differentiated GEP-NETs, and 4 (3.7%) with GISTs. One patient had primary hyperparathyroidism, 1 patient had medullary microcarcinoma, and 16 patients had goiter, multinodular in 10 cases. There was no correlation between pheochromocytoma and other NF1 tumoral manifestations, nor correlations between pheochromocytoma and Conclusion: The pheochromocytoma prevalence in this NF1 cohort was higher (>20%) than previously described, confirming the interest of systematic screening, especially in young women. The prevalence of GEP-NETs and GISTs was about 3%, respectively. No phenotype-genotype correlation was observed.