Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease

Background. Patients with von Hippel-Lindau disease (VHL) may develop pancr eatic neuroendocrine tumors (PNETs), which can behave in a malignant fashio n. We prospectively evaluated size criteria for resection of lesions and th e role of genotype/phenotype analysis of germline VHL mutations in predicti ng clinical course. Methods. From December 1988 through December 1999 we screened 389 patients with VHL. The diagnosis of PNET was made by pathologic analysis of tissues or by radiographic appearance. Germline mutations were determined by quanti tative Southern blotting, fluorescence in situ hybridization and complete g ene sequencing. Results. Forty-four patients with PNETs have been identified; 25 have under gone surgical resection, 5 had metastatic disease, and 14 are being monitor ed. No patient who has undergone resection based on turner size criteria ha s developed metastases. Patients with PNETs were mom likely to have missens e mutations (58%), and 4 of 5 patients (80%) with metastatic disease had mu tations nz exon 3 compared with 18 of 39 (46%) patients without metastatic disease. Conclusions. Imaging-for detection and surgical resection based on size cri teria have resulted in the successful management of VHL patients with PNETs . Analysis of germline mutations may help identify patients at risk for PNE T and which patients may benefit from surgical intervention.