Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.

Circulating Angiogenic Markers in Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review

“…Next-generation sequencing has provided not only insights into the pathophysiology of NENs, but also potential targetable mutations and prognostic markers [ 31 , 32 ]. NETest (Wren Laboratories, Branford, CT, USA) is a polymerase chain reaction (PCR)-based multianalyte algorithmic assay using blood or tissue samples [ 33 ] that shows the most promising results so far in terms of predicting diagnosis, outcome and response to treatment [ 33 , 34 , 35 ], with the potential to detect tumor progression up to 2 years before radiological changes [ 36 ]. Circulating tumor cells, free circulating DNA and microRNA testing has been extrapolated in NENs and shown some potential, although further research is required [ 37 , 38 , 39 , 40 ].…”

Neuroendocrine Tumor Arising within Mature Cystic Teratoma of the Pancreas: Literature Review and Case Report

“…They are most commonly found in the gonads, but can arise in almost any structure along the midline of the body, with the pancreas among the rarest sites of occurrence [ 8 , 9 ]. Moreover, pancreatic neuroendocrine tumors are also rare heterogenous pancreatic diseases, accounting for less than 3% of all pancreatic neoplasms [ 10 , 11 ]. Consequently, to the best of our knowledge, only two cases of pancreatic teratoma with concomitant neuroendocrine tumor have been reported so far [ 5 , 6 ].…”

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

“…It can reveal recurrence and may predict prognosis. A new immunohistochemical marker is the transcription factor insulinoma-associated protein 1 (INSM1), which is more specific for the differentiation of NETs of the pancreas and rectum[ 4 , 35 , 44 , 45 ].…”

“…It has difficulties and a limited role in imaging small lesions of the stomach, duodenum and small bowel. Magnetic resonance imaging (MRI) is usually selected for preoperative staging and especially for evaluation of hepatic metastases (sensitivity 91%)[ 44 , 61 ] and their response to chemotherapy[ 62 ]. Diffusion weighted MRI and contrast enhanced MRI aid in the detection of small hepatic metastases.…”