Neuroendocrine neoplasms of the lung - The latest updates - Minireviews

Q: Which immunohistochemical markers are commonly used in lung neuroendocrine neoplasms?

Lung neuroendocrine neoplasms are typically positive for chromogranin A, synaptophysin, and CD56 (NCAM1). INSM1 has been proposed as a useful neuroendocrine marker, and ASCL1 is another transcription factor expressed only in a subgroup.

Sep 23, 2026

Uploaded by Quinn Holloway

Neuroendocrine neoplasms are heterogeneous malignant tumors that originate from neuroendocrine cells, occurring most frequently in the gastrointestinal tract and the lung. The 2021 World Health Organization classification recognizes lung neuroendocrine neoplasms as an independent group, covering typical and atypical neuroendocrine tumors as well as small cell and large cell neuroendocrine carcinomas. Despite largely unchanged terminology, clinically relevant updates affect epidemiology, clinical behavior, diagnosis, therapy, and prognosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Classification of lung neuroendocrine neoplasms

Histopathological criteria and grading

Diagnostic biomarkers and evaluation

| W | J | C | O | World Journal of
Clinical Oncology | | --- | --- | --- | --- | --- | Submit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Clin Oncol 2025 May 24; 16(5): 106630 DOI: 10.5306/wjco.v16.i5.106630 ISSN 2218-4333 (online) MINIREVIEWS Neuroendocrine neoplasms of the lung: The latest updates Riccardo Orlandi Specialty type: Oncology Provenance and peer review: Invited article; Externally peer reviewed. Peer-review model: Single blind Peer-review report’s classification Scientific Quality: Grade B Novelty: Grade C Creativity or Innovation: Grade C Scientific Significance: Grade B P-Reviewer: Ren SQ Received: March 4, 2025 Revised: March 21, 2025 Accepted: April 1, 2025 Published online: May 24, 2025 Processing time: 77 Days and 8.4 Hours Riccardo Orlandi, Department of Thoracic Surgery, University of Milan, Milan 20122, Italy Corresponding author: Riccardo Orlandi, MD, Doctor, Department of Thoracic Surgery, University of Milan, Via Festa del Perdono, 7, Milan 20122, Italy. [riccardo.orlandi@unimi.it](riccardo.orlandi@unimi.it) Abstract Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells, most frequently in the gastrointestinal tract and in the lung. The latest 2021 World Health Organization (WHO) classification of lung tumors defines neuroendocrine neoplasms of the lung as an independent group of tumors, including typical and atypical neuroendocrine tumors and small cell and large cell neuroendocrine carcinomas. Although the overall nomenclature is essentially unchanged from the fourth WHO classification, there are several clinically relevant updates. In this review article, we discuss the epidemiological, clinical, diagnostic, therapeutic and prognostic features of these fascinating neoplasms, including the latest insights, current challenges and future perspectives. Key Words: Neuroendocrine lung cancer; Carcinoid; Small cell lung cancer; Large cell neuroendocrine lung cancer; Diagnosis; Management ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved. Core Tip: Neuroendocrine neoplasms (NENs) arise from neuroendocrine cells and vary in malignancy, commonly affecting the gastrointestinal tract and lungs. The 2021 World Health Organization classification of lung tumors categorizes lung NENs into typical and atypical neuroendocrine tumors and high-grade small cell and large cell neuroendocrine carcinomas. While the classification remains largely unchanged, key clinical updates have been introduced. This review explores the epidemiology, diagnosis, treatment, and prognosis of lung NENs, highlighting emerging insights, and future directions. Citation: Orlandi R. Neuroendocrine neoplasms of the lung: The latest updates. World J Clin Oncol 2025; 16(5): 106630 URL: [https://www.wjgnet.com/2218-4333/full/v16/i5/106630.htm](https://www.wjgnet.com/2218-4333/full/v16/i5/106630.htm) DOI: [https://dx.doi.org/10.5306/wjco.v16.i5.106630](https://dx.doi.org/10.5306/wjco.v16.i5.106630) WJCO [https://www.wjgnet.com](https://www.wjgnet.com) 1 May 24, 2025 Volume 16 Issue 5 Orlandi R. Challenges and perspectives of neuroendocrine neoplasms INTRODUCTION Lung neuroendocrine neoplasms (LNNs) represent a group of uncommon tumors with multiple grades of malignancy apparently deriving from Kulchitsky cells, which are argentaffin amine precursor uptake and decarboxylation cells of the bronchial epithelium [1] . In 2021, the latest World Health Organization (WHO) classification of lung tumors affirmed LNNs as an independent group of tumors with heterogeneous malignancy [2], as previously established in 2015 [3], including low-graded typical carcinoid (TC), intermediate-graded atypical carcinoids (AC), high-graded small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as presented in Table 1. The distinction is based o

FAQs

How does the 2021 WHO classification define lung neuroendocrine neoplasms?

It classifies lung neuroendocrine neoplasms into typical and atypical neuroendocrine tumors, and into high-grade small cell and large cell neuroendocrine carcinomas as an independent tumor group.

What criteria distinguish typical carcinoid from atypical carcinoid and high-grade tumors?

The distinction relies on histopathological features, Ki-67 index, mitotic rate, and necrosis. Typical carcinoid shows <2 mitoses/2 mm² without necrosis, atypical carcinoid shows 2–10 mitoses/2 mm² or focal necrosis, while small cell and large cell neuroendocrine carcinomas have high mitotic rates with extended/diffuse necrosis.

Which immunohistochemical markers are commonly used in lung neuroendocrine neoplasms?

Lung neuroendocrine neoplasms are typically positive for chromogranin A, synaptophysin, and CD56 (NCAM1). INSM1 has been proposed as a useful neuroendocrine marker, and ASCL1 is another transcription factor expressed only in a subgroup.

Sep 23, 2026

Uploaded by Quinn Holloway