25 Years of Neuroendocrine Neoplasms of the Gastrointestinal Tract G. Rindi & G. Petrone & F. Inzani Published online: 8 January 2014 # Springer Science+Business Media New York 2014 Abstract 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. Keywords Tumor . Carcinoma . Endocrine . Neuroendocrine . Immunohistochemistry . Chormogranin A . Synaptophysin . Ki67 Introduction This paper will attempt to briefly describe the evolution of knowledge, definition and classification of gastrointestinal (GI) neuroendocrine neoplasms (NEN) as personally experi- enced by pathologists in the last 25 years. We do not aim to write a comprehensive and complete review of the multiple and diverse pieces of information accumulated slowly and with many difficulties along these years. Rather this paper aims at providing a very personal view of what was felt as relevant or what subsequently resulted so in the daily practice of pathologists facing the diagnosis of GI NENs. We certainly will not mention many contributions, so the reader is invited to forgive our limited approach and to follow this story with a light attitude. The paper is divided into two parts, the first dealing with the way GI NENs was considered and stood in the pathology and medical community in the past 25 years, and the second brief part dealing with the present day. 25 Years Ago till Today The Gastrointestinal Pathology Landscape in 1989 In the 1980s, several events occurred that were bound to significantly impact on the daily practice of GI pathologists. After years of skepticism, the scientific community accepted Helicobacter pylori (Hp ) as the cause of peptic ulcer disease and its potential role for promoting gastric mucosa-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma [1–3]. Hp detection on gastric samples is now the gold stan- dard tool for infection detection and gastric cancer prevention. Omeprazole was also introduced as first prescription proton pump inhibitor (PPI) and main co-actor with antimicrobial therapy for Hp eradication [4]. At the same time, the first genetic multistep model of cancerogenesis was unveiled and this was for colorectal can- cer [5]. Surveillance and removing of adenomatous polyps by colonoscopy soon became the main prevention tool leading to the current screening programs [6]. Overall the digestive tract became the source of multiple preventive and diagnostic investigations, mainly, but not only, by endoscopic means, and this resulted in a large vol- ume of samples for GI pathologists. More NENs were soon to be detected. G. Rindi : G. Petrone : F. Inzani Institute of Pathology, Università Cattolica del Sacro Cuore – Policlinico A. Gemelli, Largo A. Gemelli, 8, 00168 Rome, Italy G. Rindi (*) Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore – Policlinico Gemelli, Largo A. Gemelli, 8, 00168 Roma, Italy e-mail: guido.rindi@rm.unicatt.it Endocr Pathol (2014) 25:59–64 DOI 10.1007/s12022-013-9292-5