Incidentally discovered, intentionally managed: a narrative review of the last decade’s updates on the management of neuroendocrine tumor of the appendix - Review article

Sep 23, 2026

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Appendiceal neuroendocrine neoplasms are an increasingly recognized, heterogeneous subset of gastroenteropancreatic neuroendocrine tumors, often found incidentally on appendectomy specimens. Postoperative management depends on histopathology-driven risk stratification and alignment with WHO and ENETS guidance, separating well-differentiated NETs and poorly differentiated neuroendocrine carcinomas. Tumor size, Ki-67, depth of invasion (notably mesoappendiceal involvement), and lymphovascular invasion determine treatment. Recommendations favor appendectomy for low-risk tumors and right hemicolectomy for high-risk disease, while intermediate 1.0–2.0 cm cases remain controversial. This review appraises recent evidence, refines individualized risk frameworks, and proposes evidence-based surveillance to support consistent multidisciplinary care.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Introduction

Background and clinical relevance

Histopathological risk stratification

Surgical decision-making in current guidelines

REVIEW ARTICLE Annals of Gastroenterology (2026) 39, 390-404 Incidentally discovered, intentionally managed: a narrative review of the last decade’s updates on the management of neuroendocrine tumor of the appendix Salvatore Raiaa,i, Maria Rita Gaia Livatinog, Giorgio Maria Orazig, Maria Grazia Marattab,i, Enza Gencod,i, Romina Grazia Giancipolih,i, Vittoria Rufinie,i, Ernesto Rossic, Sabrina Chiloroa, Claudio Fiorillof, Sergio Alfierif, Giampaolo Tortorab, Alfredo Pontecorvia, Guido Rindic,i, Antonio Bianchia,i*, Giovanni Schinzarib,i* Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Abstract Appendiceal neuroendocrine neoplasms (aNENs) represent an increasingly recognized and heterogeneous subset of gastroenteropancreatic neuroendocrine tumors (NETs), most often identified incidentally on appendectomy specimens. Postoperative management relies on accurate risk stratification grounded in histopathological assessment and aligned with major international guidelines (WHO, ENETS), which distinguish between well-differentiated NETs (NET grades 1 to 3) and poorly differentiated neuroendocrine carcinomas. Critical prognostic determinants shaping therapeutic decision-making include tumor size, proliferative index (Ki-67), depth of invasion—particularly mesoappendiceal involvement—and lymphovascular invasion (LVI) . Consensus recommendations suggest simple appendectomy as definitive treatment for low-risk tumors (<1 cm) and right hemicolectomy for high-risk lesions (>2 cm) or those exhibiting LVI. However, the management of intermediate-sized aNENs (1.0- 2.0 cm) remains the principal area of clinical uncertainty, with emerging data suggesting that appendectomy alone may be sufficient for carefully selected patients without adverse pathological factors. This review synthesizes and critically appraises the most recent evidence and international guidelines with the goal of refining current clinical practice. In particular, it provides an updated framework for individualized risk stratification, evaluates the balance between oncological benefit and procedural morbidity in determining the optimal surgical approach, and outlines evidence-based surveillance strategies to support a more consistent, risk-adapted multidisciplinary management of aNENs. Keywords Appendiceal neuroendocrine tumor, neuroendocrine neoplasms, surgical management, right hemicolectomy, ENETS guidelines Ann Gastroenterol 2026; 39 (4): 390-404 Conflict of Interest: None *Co-senior authors (shared last authorship) Correspondence to: Salvatore Raia, MD, Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy, e-mail: [salvatore.raia1@unicatt.it](salvatore.raia1@unicatt.it) Received 19 February 2026; accepted 21 March 2026; published online 28 May 2026 DOI: [https://doi.org/10.20524/aog.2026.1070](https://doi.org/10.20524/aog.2026.1070) This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercialShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms Introduction Neuroendocrine neoplasms (NENs) represent a biologically and clinically heterogeneous group of tumors arising from the diffuse neuroendocrine cell system, with the gastroenteropancreatic (GEP) tract recognized as the principal site of origin, a point repeatedly underscored by leading international guidelines [1]. While general guidelines provide a comprehensive overview of diagnosis and treatment, the specific clinical approach often requires further refinement based on the primary site [2] . Within the GEP system, appendiceal NENs (aNENs) constitute a distinct and relatively rare entity, typically accounting for a small percentage of appendecto

FAQs

How are appendiceal neuroendocrine neoplasms typically identified?

They are most often detected incidentally on appendectomy specimens performed for suspected acute appendicitis.

Which prognostic factors guide postoperative management?

Tumor size, Ki-67 proliferative index, depth of invasion (including mesoappendiceal involvement), and lymphovascular invasion, alongside margin status, are used for risk stratification.

What treatment is generally recommended for low-risk versus high-risk tumors?

Simple appendectomy is recommended for low-risk tumors (<1 cm), whereas right hemicolectomy is suggested for high-risk lesions (>2 cm) or those with lymphovascular invasion.

Sep 23, 2026

Uploaded by Bulrr