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Louis de Mestier Université de Paris, Department of Gastroenterology-Pancreatology, Beaujon University Hospital (APHP), Clichy, France

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Angela Lamarca Division of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation, University of Manchester, Manchester, United Kingdom

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Jorge Hernando Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Wouter Zandee Department of Internal Medicine, Sector Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Division of Endocrinology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Teresa Alonso-Gordoa Department of Medical Oncology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain

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Marine Perrier Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France

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Annemiek ME Walenkamp Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

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Bipasha Chakrabarty Department of Pathology, The Christie, Manchester, United Kingdom

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Stefania Landolfi Department of Pathology, Vall d’Hebron University Hospital, Barcelona, Spain

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Marie-Louise F Van Velthuysen Department of Pathology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Gursah Kats-Ugurlu Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Alejandra Caminoa Department of Pathology, University Hospital Ramon y Cajal, Madrid, Spain

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Maxime Ronot Université de Paris, Department of Radiology, Beaujon University Hospital (APHP), Clichy, France

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Prakash Manoharan Department of Radiology and Nuclear Medicine, The Christie, Manchester, United Kingdom

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Alejandro Garcia-Alvarez Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Tessa Brabander Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

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María Isabel García Gómez-Muriel Department of Radiology, University Hospital Ramon y Cajal, Madrid, Spain

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Guillaume Cadiot Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France

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Anne Couvelard Université de Paris, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France

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Jaume Capdevila Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Marianne E Pavel Department of Endocrinology, Erlangen University Hospital, Erlangen, Germany

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Jérôme Cros Université de Paris, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France

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Introduction The classification of neuroendocrine neoplasms (NENs) relies on differentiation (well-differentiated neuroendocrine tumors (NETs) or poorly-differentiated neuroendocrine carcinomas (NECs)) and the proliferation index, which is

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Julien Hadoux Oncologie Endocrinienne, Département d’Imagerie, Gustave Roussy, Villejuif, France

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Thomas Walter Service d’Oncologie, ENETS Centre of Excellence, Hospices Civils de Lyon et Université de Lyon, Lyon, France

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Christina Kanaan Service de Pathologie, Département de Biologie et Pathologie Médicale, Gustave Roussy, Villejuif, France

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Ségolène Hescot Département d’Oncologie, Institut Curie, Paris, France

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Vincent Hautefeuille Service d’Hépato-gastro-entérologie et Cancérologie Digestive, CHU Amiens Picardie, Amiens, France

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Marine Perrier Département d’Hépato-gastro-entérologie, CHU de Reims, Reims, France

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Igor Tauveron Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, CHU Clermont-Ferrand, Clermont-Ferrand, France
Laboratoire GReD, Université Clermont Auvergne, Clermont-Ferrand, France

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Sandrine Laboureau Département d’Endocrinologie-Diabétologie-Nutrition, CHU d’Angers, Angers Cedex 9, France

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Christine Do Cao CHU de Lille, Service d’Endocrinologie, Lille, France

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Caroline Petorin CHU Clermont-Ferrand, Service de Chirurgie Digestive et Hépatobiliaire, Clermont-Ferrand, France

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Odile Blanchet CRB, CHU d’Angers, Angers Cedex 9, France

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Matthieu Faron Département de Chirurgie, Gustave Roussy, Villejuif, France

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Emmanuelle Leteurtre CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Université de Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, Lille, France

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Marie-Christine Rousselet Département de Pathologie, CHU d’Angers, Angers Cedex 9, France

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Juliette Joubert Zakeyh Laboratoire d’Anatomie Pathologique, CHU Clermont-Ferrand, Clermont-Ferrand, France

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Aude Marchal Service d’Anatomo-Pathologie, CHU Reims, Reims, France

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Denis Chatelain Service d’Anatomo-Pathologie, CHU Amiens, Amiens, France

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Clément Beaulaton Service d’Anatomo-Pathologie, Institut Curie, Paris, France

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Valérie Hervieu Service d’Anatomo-Pathologie, ENETS Centre of Excellence, Hospices Civils de Lyon et Université de Lyon, Lyon, France

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Catherine Lombard-Bohas Service d’Oncologie, ENETS Centre of Excellence, Hospices Civils de Lyon et Université de Lyon, Lyon, France

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Michel Ducreux Service d’Oncologie Digestive, Département de Médecine, Gustave Roussy, Villejuif, France
Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, France

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Jean-Yves Scoazec Service de Pathologie, Département de Biologie et Pathologie Médicale, Gustave Roussy, Villejuif, France
Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, France

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Eric Baudin Oncologie Endocrinienne, Département d’Imagerie, Gustave Roussy, Villejuif, France

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the Groupe d’Etude des Tumeurs Endocrines (GTE)
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the ENDOCAN-RENATEN network
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Patients This was a multicentre retrospective study of seven tertiary centres of the French expert network for the management of neuroendocrine neoplasms ENDOCAN-RENATEN (approved by the French National Cancer Institute, INCa). Patients were diagnosed

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Igryl S Cordero-Hernandez Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Alicia C Ross Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Arvind Dasari Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Daniel M Halperin Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Beth Chasen Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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James C Yao Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Introduction Neuroendocrine neoplasms (NEN) are a heterogenous group of malignancies, most commonly arising from gastroenteropancreatic (GEP) sites, with increasing incidence and prevalence worldwide ( Dasari et al. 2017 , Das & Dasari 2021

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Mairéad G McNamara Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
Division of Cancer Sciences, University of Manchester, Manchester, UK

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Jean-Yves Scoazec Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France
Université Paris Sud, Faculté de Médecine de Bicêtre, Le Kremlin-Bicêtre, France

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Thomas Walter Department of Gastroenterology and Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France

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al . 2016 , McNamara et al . 2019 ). There has been recent progress in the pathological diagnosis of high grade neuroendocrine neoplasms (NENs) ( Lloyd et al . 2017 , Rindi et al . 2018 a ) and in the description of their molecular and immune

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Ophélie De Rycke Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France
Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France

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Thomas Walter Department of Gastro-enterology and oncology, Hospices Civils de Lyon, Edouard Herriot University Hospital, Lyon, France

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Marine Perrier Department of Hepato-Gastroenterology and Digestive Oncology, Robert Debré University Hospital, Reims, France

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Olivia Hentic Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France

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Catherine Lombard-Bohas Department of Gastro-enterology and oncology, Hospices Civils de Lyon, Edouard Herriot University Hospital, Lyon, France

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Romain Coriat Department of Gastroenterology, Cochin University Hospital, Paris, France

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Guillaume Cadiot Department of Hepato-Gastroenterology and Digestive Oncology, Robert Debré University Hospital, Reims, France

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Anne Couvelard Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospital, Paris/Clichy, France

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Philippe Ruszniewski Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France
Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France

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Jérôme Cros Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospital, Paris/Clichy, France

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Louis de Mestier Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France
Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France

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, 2018 Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study . Endocrine 60 490 – 498 . ( https://doi.org/10.1007/s12020

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S Felder Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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H Jann Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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R Arsenic Institut für Pathologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany

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T Denecke Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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V Prasad Klinik für Nuklearmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Klinik für Nuklearmedizin, Universitätklinikum Ulm, Ulm, Germany

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B Knappe-Drzikova Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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S Maasberg Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany

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B Wiedenmann Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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M Pavel Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum der Friedrich-Alexander Universität Erlangen, Erlangen, Germany

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A Pascher Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uinversitätsklinikum Münster, Münster, Germany

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U F Pape Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany

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G Fazio N , et al . 2016 Clinical management of patients with gastric neuroendocrine neoplasms associated with chronic atrophic gastritis: a retrospective, multicentre study . Endocrine 51 . ( https://doi.org/10.1007/s12020-015-0584-z

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Kjell Oberg Department of Endocrine Oncology, Department of Medical Sciences, University Hospital, Entrance 78, SE-751 85 Uppsala, Sweden
Department of Endocrine Oncology, Department of Medical Sciences, University Hospital, Entrance 78, SE-751 85 Uppsala, Sweden

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classification and the pathology of gastro-entero-pancreatic neuroendocrine neoplasms is discussed by Prof. Günter Klöppel ( Klöppel 2011 ). A number of biomarkers has been developed during the last decades based on development of the immunoassays for various gut

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Frank Weber Division of Endocrine Surgery Department of General-, Visceral- and Transplantations Surgery, Medical Faculty, University of Duisburg-Essen, Essen, Germany

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Lois M Mulligan Division of Cancer Biology and Genetics Cancer Research Institute, Queen’s University, Kingston, Canada

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-endocrine manifestations (i.e., adrenocortical neoplasm, thymic and bronchial neuroendocrine neoplasms, breast and soft tissue tumors) beyond the parathyroid adenoma, gastrinoma and prolactinoma described originally, and also to understand the genetic, epigenetic and post

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Anela Blažević Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Anand M Iyer Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Marie-Louise F van Velthuysen Department of Pathology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Johannes Hofland Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Gaston J H Franssen Department of Surgery, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Richard A Feelders Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Marina Zajec Laboratory of Neuro-Oncology/Clinical & Cancer Proteomics, Department of Neurology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Theo M Luider Laboratory of Neuro-Oncology/Clinical & Cancer Proteomics, Department of Neurology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Wouter W de Herder Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Leo J Hofland Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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small bowel neuroendocrine neoplasms . Endocrine 67 718 – 726 . ( https://doi.org/10.1007/s12020-019-02107-4 ) Laskaratos FM Walker M Wilkins D Tuck A Ramakrishnan S Phillips E Gertner J Megapanou M Papantoniou D Shah R , 2018

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Massimo Milione 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

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Patrick Maisonneuve Division of Epidemiology and Biostatistics, European Institute of Oncology (IEO), Milan, Italy

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Alessio Pellegrinelli 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

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Federica Grillo Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova and Policlinico San Martino, Genova, Italy

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Luca Albarello Pathology Unit, IRCCS San Raffaele Scientifica Institute, Milan, Italy

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Paola Spaggiari Cancer Center Humanitas, Milan, Italy

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Alessandro Vanoli Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy

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Giovanna Tagliabue Lombardy Cancer Registry, Varese Province Cancer Registry Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

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Eleonora Pisa Division of Pathology, European Institute of Oncology (IEO), Milan, Italy

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Luca Messerini Diagnostic and Molecular Pathology, Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy

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Giovanni Centonze Department of Experimental Oncology and Molecular Medicine, Unit of Tumor Genomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Clinical Research Lab (CRAB), Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

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Frediano Inzani Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy

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Aldo Scarpa ARC-Net Research Centre and Department of Diagnostics and Public Health-Section of Pathology, University and Hospital Trust of Verona, Verona, Italy

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Mauro Papotti Department of Oncology, University of Turin, Turin, Italy

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Marco Volante Department of Oncology, University of Turin, Turin, Italy

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Fausto Sessa Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Nicola Fazio Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit, European Institute of Oncology (IEO), Milan, Italy

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Giancarlo Pruneri 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
University of Milan, School of Medicine, Milan, Italy

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Guido Rindi Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore-Fondazione Policlinico Universitario A. Gemelli, Rome, Italy

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Enrico Solcia Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy

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Stefano La Rosa Service of Clinical Pathology, Lausanne University Hospital, Institute of Pathology, Lausanne, Switzerland

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Carlo Capella Department of Medicine and Surgery, University of Insubria, Varese, Italy

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widely shown to be an important diagnostic tool for neuroendocrine neoplasms, this study, has added new and interesting findings with regards to the importance of proliferation in MANECs as well. Indeed, as previously reported for pure NECs ( Sorbye et

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