Neuroendocrine Tumors: A Multidisciplinary Approach

M. Papotti, W. W. de Herder, M., Papotti, W.W., de Herder, Federica Guaraldi, Giovanni Corona, Federica, Guaraldi, Giovanni, Corona

• Publisher: S. Karger
• Year: 2015
• Print ISBN: 9783318027723
• eBook ISBN: 9783318027730
• Topic: Medicine
• Subtopic: Gastroenterology & Hepatology

The term 'carcinoid' entered medical literature over 100 years ago to describe a peculiar intestinal epithelial neoplasm. Since then, a large body of literature has expanded the concept of carcinoid, later replaced by the term 'NeuroEndocrine Tumor' (NET), defining a wide spectrum of peculiar tumors, potentially affecting all organs and tissues, originating from neuroendocrine cells, sharing, but, at the same time, keeping, pathognomonic pathological, radiological and clinical features. This book provides an authoritative overview of the epidemiological, clinical, genetic, molecular and pathological characteristics of NETs and highlights the most relevant controversial issues in the classification, diagnosis and therapy. Furthermore the new frontiers in the field of medical therapies are presented, through a multidisciplinary and translational approach. Considering the fact that NETs have been recently demonstrated less rare as considered so far, 'Neuroendocrine Tumors: A Multidisciplinary Approach' is a must read for endocrinologists, gastroenterologists, endocrine surgeons, as well as pathologists, nuclear medicine physicians and radiologists focused on NET.

Papotti M, de Herder WW (eds): Neuroendocrine Tumors: A Multidisciplinary Approach.
Front Horm Res. Basel, Karger, 2015, vol 44, pp 1-23 (DOI: 10.1159/000381970)

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Epidemiology of Neuroendocrine Tumors

Merav Fraenkel^a · Antongiulio Faggiano^b · Gerlof D. Valk^c

^aEndocrinology Unit, Soroka University Medical Center and The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; ^bDepartment of Molecular and Clinical Endocrinology and Metabolism, Federico II University of Naples, Napoli, Italy; ^cDepartment of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

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Abstract

Formerly named carcinoids, neuroendocrine tumors originate from diffuse endocrine cells, can involve any part of the gastrointestinal tract, endocrine pancreas and bronchopulmonary (BP) tree, and have a wide range of malignant potential. This chapter summarizes the data available on the epidemiology of neuroendocrine neoplasia (NEN) from around the world, including the relative frequency according to organ of origin, annual incidence rates (IR) and trends in IR at the various anatomic sites, age and stage at presentation, racial and gender differences in IR and 5-year survival rates. Over time, changes have been made in the classification and registration of NEN, both in the same registry and across the globe, thus confounding the possibility to draw conclusions as to the true rise in IR of NEN that is observed all over the world. BP NEN has become the most common site in many western countries, while NEN of the rectum is more common in the Far East. In some countries, appendiceal NEN is the most common site in females. When compared to adenocarcinoma of the same location, the prognosis of NEN patients is better. Five-year survival rates are highest for NEN originating in the rectum and appendix, but lower in small intestinal and pancreatic NEN. Future research is needed to understand the contribution of genetic and environmental factors to NEN epidemiology.

© 2015 S. Karger AG, Basel

Neuroendocrine tumors (NETs) originate from diffuse neuroendocrine cells that are dispersed throughout the body, predominantly in the gastrointestinal tract, islets of Langerhans in the pancreas and the bronchopulmonary (BP) system. Neuroendocrine cells are unique in their capability to synthesize and secrete neuropeptides and hormones, leading to characteristic hormonal syndromes. NETs are comprised of cells that on immunohistochemistry may be identified by specific neuroendocrine markers, such as synaptophysin and chromogranin A. NETs are a heterogeneous group of tumors causing unique clinical syndromes and/or local symptoms, but, not uncommonly, may also be asymptomatic and discovered as an incidental finding [1].

NETs of the gastrointestinal tract were originally described by Oberndorfer in 1907, who coined the name ‘Karzinoide’ to describe submucosal tumors in the small bowel which followed an indolent course when compared to adenocarcinoma. The first description of BP NETs was made by Laennec about 100 years earlier [1].

Histologic Classification of Neuroendocrine Tumors

Major changes have been made in the classification of NETs throughout the years. The most widely accepted is the WHO classification, which is based on the histologic grade (according to the Ki-67 and mitotic index) and degree of differentiation (well vs. poorly differentiated) [2]. This new classification argues against the use of the term ‘carcinoid’ combined with the organ from which this tumor originated, as this may be misleading and does not reflect the diversity of malignant potential that these tumors may carry. The most recent WHO 2010 system renders all NETs as neoplasms with a malignant potential and calls for the use of the term neuroendocrine neoplasia (NEN) [3, 4]. This is in contrast to the older paradigm assuming these are rare, slow-growing tumors with an indolent behavior. Unfortunately, this new terminology of NEN has not yet been fully accepted around the world. Moreover, some publications still classify NEN according to the embryonic source of the organ. These complexities in classification and grading are further accentuated in the terminology of BP NEN. The most recent WHO classification of BP NEN, published in 2004, mainly relies on morphology, with the aid of mitotic count and assessment of the presence of necrosis, and divides BP NEN into 4 subtypes [3-5]. A grading system based on the Ki-67 index for BP NEN has recently been introduced but has not been officially accepted yet [6].

Coding Systems of Neuroendocrine Tumors

Most, but not all, national and local cancer registries used the International Classification of Disease for Oncology (ICD-O) coding system to collect data on the epidemiology of these NEN. This coding system has been updated periodically and, therefore, early reports are often incompatible with more recent data. The latest ICD-O-3, used for the coding of NEN, is presented in table 1. The first 4 digits designate the histologic diagnosis and the fifth digit, designated as ‘behavior code’, reports the biologic behavior according to the following: 0 = benign, 1 = borderline malignancy, 2 = in situ, 3 = malignant (http://seer.cancer.gov/behavrecode/). In addition, the anatomic site of the tumor is recorded.

Table 1. ICD-O codes for NETs

NET histology	ICD code
Carcinoid tumor	8240
Enterochromaffin cell carcinoid	8241
Goblet cell carcinoid	8243
Composite carcinoid	8244
Adenocarcinoid	8245
Neuroendocrine carcinoma	8246
Apudoma	8248
AC	8249
Stromal carcinoid	9091
Islet cell carcinoma	8150
Insulinoma	8151
Glucagonoma	8152
Gastrinoma	8153
Mixed islet cell/exocrine adenocarcinoma	8154
VIPoma	8155
Somatost...

Table of contents

• Cover Page
• Front Matter
• Epidemiology of Neuroendocrine Tumors
• Biochemical Testing in Patients with Neuroendocrine Tumors
• Clinical Syndromes Related to Gastrointestinal Neuroendocrine Neoplasms
• Radiological Imaging: Computed Tomography, Magnetic Resonance Imaging and Ultrasonography
• Nuclear Medicine Imaging of Neuroendocrine Tumors
• Endoscopy and Endoscopic Ultrasound in Assessing and Managing Neuroendocrine Neoplasms
• Pathology: Classification and Immunoprofile
• Genetics and Epigenetics of Pancreatic Neuroendocrine Tumors and Pulmonary Carcinoids
• Pancreatic Surgery
• Gastrointestinal Surgery of Neuroendocrine Neoplasms
• Transplantation and Debulking Procedures for Neuroendocrine Tumors
• A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy
• Medical Therapy of Pulmonary Neuroendocrine Neoplasms: Targeted, Symptomatic and Chemotherapy
• Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors
• Hormone and Receptor Candidates for Target and Biotherapy of Neuroendocrine Tumors
• The Role of Chemotherapy in Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors
• Other Novel Therapies: Biomarkers, microRNAs and microRNA Inhibitors, DNA Methylation, Epigenetics, Immunotherapy and Virotherapy
• Author Index
• Subject Index