JOURNAL OF THE ITALIAN SOCIETY OF ANATOMIC PATHOLOGY AND DIAGNOSTIC CYTOPATHOLOGY, ITALIAN DIVISION OF THE INTERNATIONAL ACADEMY OF PATHOLOGY Periodico trimestrale - Aut. Trib. di Genova n. 75 del 22/06/1949 ISSN: 1591-951X (Online) The GIPAD handbook of the gastrointestinal pathologist (in the Covid-19 era) - Part II 01VOL. 113 Edited by Paola Parente and Matteo Fassan FEBRUARY 2021 Editor-in-Chief C. Doglioni G. Pelosi M. Barbareschi San Raffaele Scientific Institute, Milan University of Milan Service of Anatomy and M. Fassan F. Pierconti University of Padua Pathological Histology, Trento Catholic University of Sacred G. Fornaciari Heart, Rome Associate Editor University of Pisa M. Chilosi M.P. Foschini S. Pileri Department of Pathology, Verona Bellaria Hospital, Bologna Milano European Institute of University, Verona G. Fraternali Orcioni Oncology, Milan S. Croce e Carle Hospital, Cuneo 01Vol. 113 P. Querzoli Managing Editor E. Fulcheri St Anna University Hospital, Ferrara University of Genoa February 2021 P. N oz za L. Resta M. Guido Pathology Unit, Ospedali Galliera, University of Bari Genova, Italy University of Padua S. Lazzi G. Rindi Catholic University of Sacred Italian Scientific Board University of Siena L. Leoncini M. Brunelli Heart, Rome University of Siena E.D. Rossi University of Verona C. Luchini G. Bulfamante Catholic University of Sacred University of Verona University of Milano G. Magro Heart, Rome G. Cenacchi University of Catania A.G. Rizzo University of Bologna E. Maiorano “Villa Sofia-Cervello” Hospital, C. Clemente University of Bari Aldo Moro Palermo San Donato Hospital, Milano A. Marchetti G. Rossi M. Colecchia University of Chieti-Pescara Hospital S. Maria delle Croci, IRCCS National Cancer Institute, G. Marucci Azienda Romagna, Ravenna Milan Bellaria Hospital, Bologna P. Cossu-Rocca G. Martignoni G. Santeusanio University of Sassari IRCCS Sacro Cuore Don Calabria University of Rome “Tor Vergata G. d’Amati Hospital, Negrar, Verona L. Saragoni Sapienza University of Rome G. Negri Morgagni-Pierantoni Hospital, Forlì E. d’Amore Pathology Unit Central Hospital G. Tallini San Bortolo Hospital, Vicenza Bolzano University of Bologna A. D’Errico A. Orlandi L. Ventura S. Orsola-Malpighi Hospital, University of Rome “Tor Vergata” University of Bologna M. Paulli San Salvatore Hospital, L’Aquila P.A. Dei Tos University of Pavia; IRCCS San G. Zamboni University of Padua Matteo Hospital Foundation, Pavia University of Verona International Scientific Board Governing Board SIAPEC-IAP R. Alaggio President: Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA A. Sapino G. Bhagat University of Torino Columbia University, New York, USA Past President: A. Capitanio M. Truini Linköping University Hospital, Likping, Sweden Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda, Milan T.V. Colby Mayo Clinic Scottsdale, AZ, USA President Elect: G. Cserni F. Fraggetta University of Szeged, Szeged, Hungary Cannizzaro Hospital, Catania, Italy S. Di Palma General Secretary: Royal Surrey County Hospital, Guilford, UK E. Bonoldi J. Fukuoka Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan Nagasaki University, Nagasaki, Japan Councillors: C. Giannini E. Bonoldi Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan MN, USA E. Fulcheri J. Kulka University of Genoa Semmelweis University, Budapest, Hungary A. Parafioriti T. Mentzel Gaetano Pini Hospital, Milan Dermatopathology Bodensee, Friedrichshafen, Baden-Württemberg Germany G.F. Zannoni M. Mihm Catholic University of Sacred Heart, Rome Brigham and Women’s Hospital, Harvard Medical School, Boston, Massa- chusetts, USA Representative L. Pantanowitz University/IRCCS: University of Pittsburgh Medical Center, Pittsburgh, PA, USA E. Maiorano M. Reyes-Múgica University of Bari UPMC Children’s Hospital of Pittsburgh; University of Pittsburgh School of Hospital/Individuals Medicine, Pittsburgh, PA, USA L. Molinaro F. Roncaroli City of Health and Science, Turin Imperial College of London, UK A. Skálová Junior counsellor: Charles Univesity, Plzen, Czech Republic V. L’Imperio M. Smith San Gerardo Hospital, University of Milano-Bicocca, Monza Mayo Clinic Scottsdale, AZ, USA Citology Board: S. Suster G. Fadda Medical College Wisconsin, Milwaukee, WI, USA Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome Y. Zen G. Negri King’s College Hospital & King’s College London, UK Central Hospital Bolzano Coord. National Council: Editorial Secretariat M. Guido F. Pedica University of Padua School of Medicine San Raffaele Scientific Institute, Milan L. Saragoni Morgagni-Pierantoni Hospital, Forlì F. Tallarigo Public Health Unit, COR Calabria, Crotone APOF Representative: G. Dell’Antonio San Raffaele Scientific Institute, Milan AITIC Representative: Moris Cadei ASST Spedali Civili-Unibs, Brescia Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology Publisher Pacini Editore S.r.l. Via Gherardesca, 1 56121 Pisa, Italy Tel. +39 050 313011 Fax +39 050 3130300 [email protected] www.pacinimedicina.it CONTENTS PATHOLOGICA 01 February 2021 REVIEWS Introduction to neuroendocrine neoplasms of the digestive system: definition and classification F. Inzani, G. Rindi ......................................................................................................................................................................................... 1 Neuroendocrine neoplasms of the esophagus and stomach L. Mastracci, G. Rindi, F. Grillo, E. Solcia, M. Campora, M. Fassan, P. Parente, A. Vanoli, S. La Rosa ......................................................... 5 Neuroendocrine neoplasms of the duodenum, ampullary region, jejunum and ileum M. Milione, P. Parente, F. Grillo, G. Zamboni, L. Mastracci, C. Capella, M. Fassan, A. Vanoli ..................................................................... 12 Neuroendocrine neoplasms of the appendix, colon and rectum M. Volante, F. Grillo, F. Massa, F. Maletta, L. Mastracci, M. Campora, J. Ferro, A. Vanoli, M. Papotti ......................................................... 19 Neuroendocrine neoplasms of the biliary tree, liver and pancreas: a pathological approach C. Luchini, G. Pelosi, A. Scarpa, P. Mattiolo, D. Marchiori, R. Maragliano, F. Sessa, S. Uccella ................................................................. 28 Histopathology of IBD Colitis. A practical approach from the pathologists of the Italian Group for the study of the gastrointestinal tract (GIPAD) V. Villanacci, L. Reggiani-Bonetti, T. Salviato, G. Leoncini, M. Cadei, L. Albarello, A. Caputo, M.C. Aquilano, S. Battista, P. Parente ................................................................................................................................................................................. 39 Histopathology of Non-IBD Colitis. A practical approach from the Italian Group for the study of the gastrointestinal tract (GIPAD) V. Villanacci, L. Reggiani-Bonetti, G. Leoncini, P. Parente, M. Cadei, L. Albarello, G. Mandelli, A. Caputo ................................................. 54 Front cover: A duodenal gastrinoma, showing a trabecular pattern, with vascular pseudorosettes (A, hematoxylin and eosin), and tumor cell reactivity for gastrin (B, gastrin immunostaining); An ampullary-type somatostatin- producing neuroendocrine tumor, showing tubulo-acinar structures with psammoma bodies in a solid/trabecular architectural background (A, hematoxylin and eosin), and extensive somatostatin expression by tumor cells (B, somatostatin immunostaining) (page 14). PATHOLOGICA 2021;113:1-4; DOI: 10.32074/1591-951X-227 Review Introduction to neuroendocrine neoplasms of the digestive system: definition and classification Frediano Inzani1,3, Guido Rindi1-3 1 Anatomic Pathology Section, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy; 2 Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; 3 ENETS Center of Excellence, Roma, Italy Summary Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined neuroendocrine. This broad definition comprises tumors found at different sites of the body with similar morphology but different behavior and genetic background. From a clinical standpoint neuroendocrine neoplasms may be functioning, when they give rise to unregulated secretion of hormones. Functioning tumors account for about one-third of neuroendocrine neoplasms. From a pathological standpoint neuroendo- crine neoplasm are classified by cancer category, cancer families/classes, cancer types, cancer grade and cancer stage. The category identifies the cancer major trait and thus defined as neuroendocrine neoplasia (NEN) to comprise all families/classes of neuroen- docrine cancer. The cancer family/types are neuroendocrine tumors (NET) as well differen- tiated, and neuroendocrine carcinoma (NEC) as poorly differentiated forms. Cancer grade, Received: November 21, 2020 Accepted: November 23, 2020 based on proliferation measure by mitotic count and Ki-67%, and cancer stage, based on tumor size and invasion (T), node deposits (N) and distant metastases (M), complete the Correspondence pathological classification. Site-specific differences are the rule. Still missing is a genetic Guido