Concomitant pancreatic neuroendocrine tumors in hereditary tumor syndromes: who, when and how to operate?

• Main Authors: Xu Han, PhD, MD, Wenhui Lou, PhD, MD
• Format: Article
• Language: English
• Published: Wolters Kluwer Health/LWW 2019-06-01
• Series: Journal of Pancreatology
• Online Access: http://journals.lww.com/10.1097/JP9.0000000000000016

Abstract. Pancreatic neuroendocrine tumors (pNETs) might present as part of a complex of hereditary (familial) syndromes caused by germline mutations such as multiple endocrine neoplasia type 1 (MEN1), von Hippel–Lindau syndrome (VHL), tuberous sclerosis, and neurofibromatosis syndromes. Hereditary pNETs are frequently misdiagnosed because their presentation may mimic other more common diseases, resulting in diagnostic delays. Although non-operative (conservative) management could be advocated in select cases in most patients, hereby avoiding surgery without loss of oncological safety, some cases still need operative intervention before malignancy develops. The objective of this review is to address the most recent literature and the evidence it provides for the indications, timing and options of operative treatment for concomitant pNETs in hereditary tumor syndromes. Complete sequencing of the whole gene is recommended for suspected hereditary pNETs. Proven functional pNETs with hereditary tumor syndromes is a good indication for surgical treatment. Conservative management for MEN1 patients with a non-functional pNET of 2 cm or smaller is associated with a low risk of malignant transformation and metastasis development. VHL-related pNETs patients with tumor size >1.5 cm or a missense mutation or any mutation type in exon 3 may benefit from surgical intervention. The parenchyma-sparing surgical strategy should be preferentially performed whenever possible in all hereditary syndromes. The decision to recommend surgery to prevent malignant transformation and tumor spread, which is based on multidisciplinary expertise and the patient's preference, should be balanced with operative mortality and morbidity.