Management recommendations for pancreatic manifestations of von Hippel–Lindau disease

Abstract

The Pancreatic Manifestations Recommendations Development Subcommittee of the VHL Alliance Von Hippel-Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018-2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL-related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL-related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL-related pancreatic manifestations.

A rare case of pancreatic macrocystic serous cystadenoma in an adolescent: a case report and literature review

“…The percentage of pancreatic neuroendocrine tumors among VHL-disease patients has been reported to range between 8% and 17%, and cystadenoma can occasionally be found in VHL disease. 25,26 So far, MSC alone without other tumors has been observed in this patient for 2 years, and there is no associated family history of VHL disease.…”

Too Familiar To Be a Coincidence? A Remarkable Headache

“…3 Otherwise, pancreatic cystic lesions have no malignant potential and do not require intervention, except for exceptional cases of specific symptoms owing to compression (enteric, biliary) of large cysts. 1 The patient had normal measurements of catecholamine metabolites. Medullar MRI was normal and abdominal imaging showed no adrenal or renal lesion.…”

“…The annual incidence of VHL is estimated between 1 in 36,000 and 1 in 43,000 live births. 1 Nearly 75% of patients with VHL disease will develop pancreatic lesions, as asymptomatic serous cystadenomas (15% of patients), simple cysts (50% of patients), and PanNET(s) (10%-20% of patients) in their lifetime. 2 Surgical resection must be discussed for PanNET associated with factors predictive of metastases, namely, a size of 30 mm or greater, doubling time of less than 500 days, and mutations in exon 3.…”

“…These patients must benefit of adapted surveillance in a center of expertise of VHL disease, for early detection of tumors to improve life expectancy, which remains low (40-52 years), owing to aggressive metastatic tumors (clear cell renal carcinoma, pheochromocytoma) or life-threatening compressing tumors (central nervous system hemangioblastomas). 1 Keywords: Hemangioblastoma; Pancreatic Neuroendocrine Tumor; Pancreatic Cysts.…”

Multidisciplinary integrated care pathway for von Hippel–Lindau disease

“…8 Several organ-specific clinical VHL guidelines have recently been published to improve care for germline VHL gene mutation carriers. [9][10][11][12] In the Netherlands, complex and highly specialized care for rare diseases such as VHL has been funneled to nationally reviewed and accredited "expertise centers," which are linked to a European Reference Network (https://ec.europa.eu/healt h/ern_en). The purpose is to improve and standardize the quality of care and to implement cost-savings by coordinated care across disciplines.…”