The spectrum and classification of gastric and duodenal neuroendocrine tumours (original) (raw)
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Gastric neuroendocrine tumors: Biology and management
Annals of Gastroenterology
Neoplasms may originate from any of the endocrine cells of the gastric wall, most commonly the enterochromaffinlike (ECL) cells of the oxyntic mucosa. In recent years, the increasing number of screening gastroscopies and biopsies, and the widespread application of sophisticated immunohistochemical stains for neuroendocrine markers, have resulted in the frequent detection of ECL tumors. The latter are regarded as a separate clinicopathological entity seen in the setting of hypergastrinemic states, and their pathogenesis follows the sequence hyperplasia dysplasia neoplasia. According to the most recent WHO classification, gastric neuroendocrine tumors (NETs) are generally divided into well-differentiated NETs (class 1a), welldifferentiated neuroendocrine carcinomas (NECs) (class 1b) and poorly differentiated NECs (class 2). Well-differentiated tumors (NETs and NECs), for which the historic term carcinoid is still in use, include three subgroups: Type I (70-80%), associated with chronic atrophic gastritis, which are benign (class 1a) ECL cell tumors in the vast majority of cases; Type II (<10%), associated with gastrinoma in patients with multiple endocrine neoplasia type1 (MEN1), which are usually benign; and Type III or sporadic (25-25%), which tend to behave aggressively (usually class 1b). Resent advances in the diagnosis and management of these tumors include the measurement of serum chromogranin-A levels, which reflect tumor mass, the use of synthetic somatostatin analogues for imaging and therapeutic purposes, and the introduction of aggressive multimodality protocols for the management of metastatic disease. Little progress has been made in the treatment of the rare, highly malignant, poorly differentiated neuroendocrine carcinomas, which are rapidly fatal, showing only short-lived responses to chemotherapy. Research is currently focusing on the study of the molecular pathways of gastric endocrine cell tumorigenesis, including the role of various growth factors and gene regulation mechanisms.
Gastric neuroendocrine tumors Chapter 1 Overview on Gastric Cancer
2017
Gastric Neuroendocrine Tumors (NET)s are classified on the basis of criteria that are common to all gastrointestinal and pancreatic neuroendocrine neoplasms. Most neuroendocrine neoplasms of the stomach are NETs –well differentiated, nonfunctioning enterochromaffin–like(ECL) cell carcinoids (ECL cell NETs)-arise predominantly in the corpus-fundus region [1]. Three distinct types are recognized :
A Clinical Perspective on Gastric Neuroendocrine Neoplasia
Current Gastroenterology Reports, 2010
The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially based on widespread use of endoscopy and a greater pathological awareness of the condition. A key concern is the potential association with hypergastrinemia induced by proton pump inhibitor administration. Previous confusion regarding diagnosis and therapy has been diminished by a series of international consensus statements defining the biology and management strategies for the disease. Overall, gastric NETs are categorized as welldifferentiated or poorly differentiated neoplasms. Welldifferentiated gastric NETs are enterochromaffin-like (ECL) cell tumors subclassified into three types based on their relationship to gastrin, a key regulator of ECL cell neoplastic transformation. The treatment of type 1 and type 2 tumors depends on the size and invasiveness of the tumor, whereas type 3 tumors and poorly differentiated neuroendocrine carcinomas warrant aggressive surgical resection. The disease-specific 5-year survival ranges from about 95% in type 1 gastric carcinoids to about 25% in poorly differentiated gastric NECs. Elucidation of the precise biology of a gastric NET is critical to diagnosis and delineation of a typespecific management strategy.
Classification and histogenesis of gastroenteropancreatic endocrine tumours
European Journal of Clinical Investigation, 2008
A series of 267 gastroenteropancreatic endocrine tumours has been revised from the point of view of histopathologic diagnosis, hormonal profile and clinical behaviour. Results of this investigation, together with revised concepts on the histogenesis of gastroenteropancreatic endocrine growths, allowed to develop detailed classification systems which proved useful for precise tumour diagnosis and for clinicopathologic correlation, with special reference to tumour function, prognosis and therapy. Among 132 pancreatic growths, various types of islet cell tumours (61 cases), with (45 cases) or without (16 cases) hyperfunctional syndrome, were separated from different types of gut-related (38 cases) and 'ectopic' (three cases) tumours, as well as from 25 non-functioning, locally symptomatic tumours, three small cell carcinomas and two mixed endocrine-exocrine tumours. Among 97 intestinal tumours, 39 argentaffin EC cell carcinoids, mostly from the appendix and ileum, were separated from 23 hindgut-type carcinoids, mostly from the rectum, 22 gastrin cell tumours, mainly from the duodenal bulb, five somatostatin cell tumours, mostly from the periampullary region of the duodenum, and two gangliocytic paragangliomas. Among 38 gastric tumours, five small cell 'neuroendocrine' carcinomas were separated from three gastrin cell tumours and 30 argyrophil carcinoids, 27 of which arose in the body fundus, 16 associated with chronic atrophic gastritis and four with combined Zollinger Ellison/Multiple Endocrine Neoplasia Syndrome.
25 Years of Neuroendocrine Neoplasms of the Gastrointestinal Tract
This paper provides a personal pathologist's view of how neuroendocrine tumors (NET) were perceived and defined in the last quarter of a century. In years when the Helicobacter pylori, omeprazole and the adenoma–carcinoma sequence in colon carcinogenesis significantly impacted on gastrointestinal (GI) pathology daily practice, neuroendocrine neoplasms of the GI tract passed from the original carcinoid definition to the current NET and neuroendocrine carcinoma (NEC) definitions. The development of different concepts, basic tumor biology knowledge, tools for pathology diagnosis and the various World Health Organization (WHO) classifications from 1980 through 2010 are briefly reviewed and discussed.
Clinicopathological profile of neuroendocrine tumors of gastrointestinal tract
IP Journal of Diagnostic Pathology and Oncology, 2020
Introduction: Neuroendocrine neoplasms are derived predominately from enterochromaffin or Kulchitsky's cells. The estimated prevalence of neuroendocrine tumors (NET) is 1 to 2 cases per 100,000 people, of which gastrointestinal tract (GIT) is the most common site. And being a rare tumor, it is less studied Aim of the Study: To study the clinicopathological profile of Neuroendocrine tumors of GIT. Materials and Methods: All specimens of neuroendocrine tumors received from the Department of Surgery and Department of digestive health diseases during the period from September 2008 to September 2012 were included. Clinical details were collected from the medical records in all cases. The tumors were classified based on WHO classification 2010 using morphological findings on H&E slides. Immunohistochemistry was done in 40 cases using Synaptophysin, Chromogranin and Neuron specific enolase. Results: There were 886 neoplasms diagnosed in GIT of which 53 (5.98%) were NET. The mean age of presentation was 50 years. The male: Female ratio observed is 2:1. The most common presenting symptoms were abdominal pain followed by loss of appetite and weight. Carcinoid syndrome was seen in 2/53 (3.8%) patients .The most common site involved was Stomach followed by duodenum and ileum. NET Grade 1 was seen in 22 cases, NET Grade 2 was seen in 9cases, NET Grade3 was seen 4 cases and mixed adenocarcinoma and neuroendocrine carcinoma (MANEC) was seen in 18 cases. Metastasis to liver was seen in 3 cases Most of the NET tumors expressed the IHC markers, 95% were positive for NSE, 87.5% were positive for Synaptophysin and 82.5% cases were positive for Chromogranin Conclusion: Neuroendocrine tumors (NETs) are uncommon malignancies of GIT. Stomach was the most common anatomical site. NET grade 1 was the most common histological subtype. IHC markers NSE, Synaptophysin and chromogranin can be used in diagnosis of NETs
Endokrynologia Polska
This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially Guidelines Grażyna Rydzewska et al. Guidelines in the World Health Organization (WHO) and North American Neuroendocrine Tumor Society (NANETS) recommendations [12, 13] (Tab. 1). 1.1.1. Pathogenesis Type 1 and type 2 tumours develop from enterochromaffin-like (ECL) cells in the gastric mucosa in response to chronic oversecretion of gastrin. Secondary hypergastrinaemia-caused by achlorhydria in the course of chronic atrophic gastritis (CAG)-is responsible for the development of GNEN type 1. Primary hypergastrinaemia-in Zollinger-Ellison syndrome (ZES), sporadic or associated with multiple endocrine neoplasia 1 (MEN-1)-is responsible for GNEN type 2. Gastrin and its derivatives stimulate the proliferation, migration, and differentiation of ECL cells, which in turn leads to their hyperplasia and dysplasia. Hypergastrinaemia, without the interaction of the transforming factor/factors, does not cause the development of GNEN [4]. Menin dysfunction may constitute a transforming factor in patients with MEN-1. The literature also mentions other factors including the following: BCL2 apoptosis inhibiting protein, p53 protein, fibroblast growth factor (FGF), transforming growth factor (TGF), Regla protein dysfunction (inhibiting the proliferation of ECL cells) [14]. 1.1.2. Type 1 Gastric neuroendocrine neoplasms type 1 (70-80% GNEN) occur in patients with atrophic gastritis. They
Histopathology of gastrointestinal neuroendocrine neoplasms
Frontiers in oncology, 2013
Gastrointestinal neuroendocrine neoplasms (GI-NENs) arise from neuroendocrine cells distributed mainly in the mucosa and submucosa of the gastrointestinal tract. In 2010, the World Health Organization (WHO) classification of NENs of the digestive system was changed, categorizing these tumors as grade 1 neuroendocrine tumor (NET), grade-2NET, neuroendocrine carcinoma (large- or small-cell type), or mixed adenoneuroendocrine carcinoma (MANEC). Such a classification is based on the Ki-67 index and mitotic count in histological material. For the accurate pathological diagnosis and grading of NENs, it is important to clearly recognize the characteristic histological features of GI-NENs and to understand the correct method of counting Ki-67 and mitoses. In this review, we focus on the histopathological features of GI-NENs, particularly regarding biopsy and cytological diagnoses, neuroendocrine markers, genetic and molecular features, and the evaluation of the Ki-67 index and mitotic count...
Endocrine Precursor Lesions of Gastroenteropancreatic Neuroendocrine Tumors
Endocrine Pathology, 2007
This review focuses on precursor lesions of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs). There are three conditions that are associated with hyperplastic changes in endocrine cells preceding GEP-NETs: autoimmune chronic atrophic gastritis or multiple endocrine neoplasia type 1 (MEN1) with gastric enterochromaffin-like (ECL) cell hyperplasia; MEN1 with gastrin and somatostatin cell hyperplasia in the duodenum and glucagon cell hyperplasia in the islets of the pancreas; and inflammatory bowel disease with endocrine cell hyperplasia in the colon. In gastric ECL cell hyperplasia, it is assumed that hypergastrinemia promotes the growth of the ECL cells of the corpus mucosa and leads to hyperplasia and neoplasia. In the duodenum and the pancreas, the MEN1-associated germline mutation of the menin gene obviously causes hyperplasia of the gastrin and somatostatin cells (duodenum) and the glucagon cells (pancreas), resulting in multifocal development of tumors. These tumors show allelic deletion of the MEN1 gene, whereas the precursor lesions retain their heterozygosity. The endocrine cell hyperplasia in the colon described in inflammatory bowel disease has neither a genetic nor a definite hormonal background.