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World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1166-1179
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1166
Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract
Sebastián Díaz-López, Jerónimo Jiménez-Castro, Carlos Enrique Robles-Barraza, Carlos Ayala-de Miguel, Manuel Chaves-Conde
Sebastián Díaz-López, Jerónimo Jiménez-Castro, Carlos Enrique Robles-Barraza, Carlos Ayala-de Miguel, Manuel Chaves-Conde, Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
Author contributions: Díaz-López S contributed to investigation, writing-original draft, writing-review & editing, and visualization; Jiménez-Castro J contributed to conceptualization, investigation, supervision, writing-review & editing, and visualization; Robles-Barraza CE and Ayala-de Miguel C contributed to investigation and writing-review & editing; Chaves-Conde M contributed to conceptualization, supervision, writing-review & editing, and visualization.
Conflict-of-interest statement: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Díaz-López: Travel expenses/Congress Support: Merck, Pfizer, LEO Pharma, IPSEN Pharma; J. Jiménez-Castro: Honoraria: Servier, Merck. Travel expenses/Congress Support: Amgen; CE Robles-Barraza: Honoraria: GSK, Aztra, Pharmamar, Roche. Travel expenses/Congress support: GSK, Aztra; C. Ayala-de Miguel: Honoraria: LEO Pharma. Travel expenses/Congress Support: Pfizer, Novartis; M. Chaves-Conde: Honoraria: Merck. Travel expenses/Congress Support: Pfizer, MSD, Merck.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jerónimo Jiménez-Castro, MD, Staff Physician, Medical Oncology Department, Hospital Universitario Valme, Ctra. de Cádiz Km. 548.9, C.P. 41014, Seville, Andalucía, Spain. jerojc@gmail.com
Received: December 6, 2023
Peer-review started: December 6, 2023
First decision: January 6, 2024
Revised: January 17, 2024
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: April 15, 2024
Abstract

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.

Keywords: Mixed neuroendocrine non-neuroendocrine neoplasms, Mixed adeno-neuroendocrine carcinomas, Mixed tumours, Gastroenteropancreatic, Treatment, Etiology, Diagnosis

Core Tip: In this review we try to clarify definition of mixed neuroendocrine (NE) non-NE tumours that have been changed along past years and analyze available evidence about their diagnosis and treatment options according to their location and extension. We have to bear in mind that we do not have validated protocols or clinical guidelines on the management of this group of diseases, although most authors propose treating mixed NE non-NE neoplasm with the high-grade NE component as treatment target. In any case, the lack of high-quality scientific evidence, based on randomised clinical trials, makes it essential to deepen our knowledge of this group of neoplasms.