When should genetic testing be performed in patients with neuroendocrine tumours?

Abstract

Neuroendocrine tumours (NETs) are a heterogenous group of tumours arising from neuroendocrine cells in several sites around the body. They include tumours of the gastroenteropancreatic system, phaeochromocytoma and paraganglioma and medullary thyroid cancer. In recent years, it has become increasingly apparent that a number of these tumours arise as a result of germline genetic mutations and are inherited in an autosomal dominant pattern. The number of genes implicated is increasing rapidly. Identifying which patients are likely to have a germline mutation enables clinicians to counsel patients adequately about their future disease risk, and allows for earlier detection of at-risk patients through family screening. The institution of screening and surveillance programmes may in turn lead to a major shift in presentation patterns for some of these tumours. In this review, we examine the features which may lead a clinician to suspect that a patient may have an inherited cause of a NET and we outline which underlying conditions should be suspected. We also discuss what type of screening may be appropriate in a variety of situations.

PDX1 DNA Methylation Distinguishes Two Subtypes of Pancreatic Neuroendocrine Neoplasms with a Different Prognosis

“…Pancreatic neuroendocrine neoplasms (PNENs) are rare neoplasms that can develop in the context of familial syndromes (10%). However, the vast majority of PNEN are sporadic occurrences (90%) [1,2]. The highest risk of developing PNENs is seen in the familial multiple endocrine neoplasia 1 (MEN1) syndrome, in which 60% of patients develop a PNEN due to germline mutations in the MEN1 gene [3].…”

What is New in the 2019 World Health Organization (WHO) Classification of Tumors of the Digestive System: Review of Selected Updates on Neuroendocrine Neoplasms, Appendiceal Tumors, and Molecular Testing

“…Patients with multiple neuroendocrine neoplasia type 1 may develop multiple duodenal gastrinomas and a subset of ampullary somatostatin expressing tumors occurs in the setting of neurofibromatosis type 1. 39 Not uncommonly, patients with small intestine NETs present with locoregional lymph node and liver metastases (in up to 35% of cases according to large population-based studies). 41 Despite this advanced presentation, these patients have a prolonged course.…”

Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients, patient advocates and NET health care professionals

“…Around 20% of NETs are associated with inherited genetic syndromes such as multiple endocrine neoplasias (MEN1/MEN2), Von Hippel–Lindau (VHL) and neurofibromatosis (NF1) . Pheochromocytomas and paragangliomas are also rare but unique NETs . Although the incidence of NETs varies from 1.51 to 6.98 per 100,000 annually, studies show an increasing trend in the incidence worldwide, possibly due to earlier and improved diagnosis.…”

“…3 Pheochromocytomas and paragangliomas are also rare but unique NETs. 4 Although the incidence of NETs varies from 1.51 to 6.98 per 100,000 annually, studies show an increasing trend in the incidence worldwide, 2,5,6 possibly due to earlier and improved diagnosis. Many patients, however, still experience diagnostic delays 5,7 and are often misdiagnosed due to nonspecific symptoms.…”