Diagnosis and Management of Hereditary Carcinoids

Carcinoid tumours arise in cells of the diffuse neuroendocrine system and can develop in a number of anatomical sites including the lungs and the gastrointestinal tract. There has been a move away from the use of the term carcinoid tumour to the more appropriate use of neuroendocrine tumour (NET) to highlight the potential for invasion and metastasis associated with some NETs. Although most cases are sporadic, 15-20% of cases are related to a hereditary syndrome, the most common of these being multiple endocrine neoplasia 1 (MEN1). Other hereditary syndromes include the following: von Hippel-Lindau (VHL), neurofibromatosis 1 and tuberous sclerosis complex (TSC), which are all associated with a germline mutation of the associated tumour suppressor gene and an autosomal dominant inheritance pattern. Familial small intestinal NET (SI NET) is a recently described condition which is also inherited in an autosomal dominant manner. There appears to be more than one causative gene; thus far, only the IPMK gene has been identified as a causative germline mutation. This was identified by carrying out whole-exome sequencing of germline and tumour DNA in a family with multiple members diagnosed with SI NET. Identification of NET predisposition genes in other families via these methods will allow the development of dedicated NET gene panels which can be used to screen NET patients and at-risk relatives for hereditary mutations. Close surveillance of at-risk individuals is important to detect NETs early when curative surgery can be offered and the morbidity and mortality of metastatic NETs can be avoided.