ArticleESMO open2024
Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.
Article in ESMO open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Distinct Molecular Pathways Driving Thymic and Pulmonary Neuroendocrine Neoplasms: Organ of Origin Defines Molecular Identity and Yields CD44 as a Marker of Pulmonary Neuroendocrine Tumors.Endocrine pathology · 2026Article
- Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids.Molecular cancer · 2026Article
- Three-Tier Prognostic Stratification of Lung Carcinoids (NET G1-G2-G3) by Multivariable, Data-Driven Integration of Ki-67 and Mitotic Count.Endocrine pathology · 2026Article
- Phosphohistone H3 and Ki-67 as prognostic markers in metastatic small intestinal neuroendocrine tumours: A comparative, retrospective cohort study.Journal of neuroendocrinology · 2026Article
- European Society of Neuroendocrine Tumors (ENETS) 2025 guidance paper for lung and thymic carcinoids.Journal of neuroendocrinology · 2026Article
- Well-Differentiated Neuroendocrine Tumors of Lung: A Case Series Supporting the IARC/WHO Common Classification of Neuroendocrine Tumor Nomenclature and Grading.Endocrine pathology · 2026Article
- Clinical utility of molecular profiling in rare lung neuroendocrine neoplasms.Frontiers in oncology · 2026Review
- A dual-validated machine learning model for predicting 3-year mortality in atypical pulmonary carcinoid, a rare neuroendocrine tumor.Frontiers in endocrinology · 2026Article
- Updates on Pulmonary Neuroendocrine Carcinoids: Progress and Perspectives.Journal of clinical medicine · 2025Review
- ONECUT2 reprograms neuroendocrine fate and is an actionable therapeutic target in small cell lung cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Review
- Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.Journal of translational medicine · 2025Article
- Basic science and translational implications of current knowledge on neuroendocrine tumors.The Journal of clinical investigation · 2025Review
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Authors and funding
47 authors.
Funding
Abstract
backgroundSix thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND
methodsPatients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm
resultsThe accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value.
conclusionsThis study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.
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