{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:28:56Z","timestamp":1786357736310,"version":"build-2736575974"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Rare lung neuroendocrine neoplasms (LNENs), including pulmonary carcinoids and large-cell neuroendocrine carcinomas (LCNEC), are heterogeneous tumors. Current World Health Organization (WHO) classification primarily relies on morphological features, leading to important inter-observer variability and sub-optimal prognostic accuracy. This review highlights the clinical utility of molecular profiling to overcome these diagnostic and prognostic challenges. Recent multi-omics studies have demonstrated that pulmonary carcinoids are not a uniform entity but comprise distinct molecular subgroups (A1, A2, B, and supra-carcinoids) with unique clinical and genomic features. Furthermore, the recently described atypical SCLC adds another layer of heterogeneity to this spectrum. For clinical practice, a biomarker panel consisting of OTP, CD44, and Ki-67 can improve the prediction of disease recurrence in pulmonary carcinoids, enabling personalized follow-up strategies. Furthermore, subgroup-specific markers, such as OTP, ASCL1, and HNF1A, may facilitate clinical implementation of molecular profiles. Within LCNEC molecular profiles are heterogenous, generally defining two major subgroups (SCLC-like and NSCLC-like). Emerging therapies targeting\n                    <jats:italic>DLL3<\/jats:italic>\n                    and\n                    <jats:italic>SEZ6<\/jats:italic>\n                    show potential relevance for clinical screening of these targets. Integration of subgroup-specific molecular markers into routine diagnostics is essential. This approach may allow clinicians to refine risk stratification, prevent unnecessary long-term surveillance, and develop personalized treatment approaches for patients with pulmonary NENs.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1840985","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:36:24Z","timestamp":1786354584000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical utility of molecular profiling in rare lung neuroendocrine neoplasms"],"prefix":"10.3389","volume":"16","author":[{"given":"Daphne","family":"Leunissen","sequence":"first","affiliation":[{"name":"Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre","place":["Maastricht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Moonen","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre","place":["Maastricht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijmen","family":"van Weert","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre","place":["Maastricht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Heijboer","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Erasmus MC Cancer Institute, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Hillen","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre","place":["Maastricht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Von der Th\u00fcsen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst-Jan","family":"Speel","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre","place":["Maastricht, Netherlands"]},{"name":"Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center","place":["Rotterdam, 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