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Large cell neuroendocrine carcinoma is a lung cancer that looks like a large-cell tumour under the microscope but has the neuroendocrine markers and the fast, aggressive behaviour of small-cell lung cancer. It sits between the two halves of the usual split, which is why teams disagree about whether to treat it as one or the other.
What it is. The fifth edition of the World Health Organization classification of thoracic tumours (2021) places large cell neuroendocrine carcinoma in the lung neuroendocrine neoplasm chapter, alongside typical carcinoid, atypical carcinoid and small cell carcinoma, rather than among the non-small-cell types it resembles by size and architecture (Nicholson 2022). The diagnosis needs both a neuroendocrine morphology, organoid nesting, rosettes or a trabecular pattern with a high mitotic count and necrosis, and confirmation of neuroendocrine differentiation by immunohistochemistry, which is why it is rarely diagnosed confidently on a small biopsy.
Where it sits in the family. It belongs to neither side of the clinical split that organises every other page in this family. The IASLC's ninth-edition staging work analysed pulmonary neuroendocrine carcinoma as its own group within the lung database, and clinical practice has run it both ways, as a non-small-cell cancer eligible for resection and adjuvant chemotherapy and as a small-cell cancer given platinum and etoposide. On this site it is a child of the lung cancer family page rather than of non-small-cell or small-cell lung cancer; the reasoning is set out in the taxonomy section of docs/CANCER-PAGES.md.
How it is treated. No randomised trial has settled it and this record does not claim one. Localised disease is resected where it can be, as for other non-small-cell tumours of the same stage, and advanced disease is generally given a platinum doublet, with the choice between the small-cell and the non-small-cell backbone decided case by case. The parent record carries the staging, the diagnostic pathway and the screening and prevention material that apply here unchanged.
What it is not. It is not large cell carcinoma, which by the 2021 definition is an undifferentiated tumour with no glandular, squamous or neuroendocrine features and is a diagnosis of exclusion made on a resection specimen. It is not small cell carcinoma, whose cells are small with scant cytoplasm and finely granular chromatin. It is not a carcinoid: typical and atypical carcinoids are low and intermediate-grade tumours with a very different course, and sit under the neuroendocrine family page in this corpus.
Rare, and counted differently depending on which classification a registry uses. GLOBOCAN does not report it, and registry series that separate the four main histological types put large cell carcinoma as a whole at 6.5 percent of lung cancers in both men and women worldwide (101,861 cases in men and 59,271 in women in 2022, Lancet Respiratory Medicine 2025); large cell neuroendocrine carcinoma is a subset of that group, so no separate incidence figure can be quoted from the sources read here.
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
Same organ: Mediastinal germ cell tumour, Pleuropulmonary blastoma (types I, Ir, II and III), Type A and type AB thymoma, Type B1 and type B2 thymoma, Type B3 thymoma, Micronodular thymoma with lymphoid stroma, Adenocarcinoma of the lung, Squamous cell carcinoma of the lung, Large cell carcinoma of the lung, Sarcomatoid carcinoma of the lung, Adenosquamous carcinoma of the lung, Invasive mucinous adenocarcinoma of the lung, Adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung, Basaloid squamous cell carcinoma of the lung, Lymphoepithelial carcinoma of the lung, Pulmonary blastoma (adult), Non-small-cell lung cancer, Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, BRAF V600E-mutant non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, NTRK fusion-positive non-small-cell lung cancer, PD-L1-high non-small-cell lung cancer without a driver mutation, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid), Thymoma (WHO types A, AB, B1, B2 and B3), Thymic carcinoma
Resection where the tumour is resectable, staged by TNM 9 as for any other lung cancer, with adjuvant chemotherapy decided case by case; no randomised trial establishes the regimen, and teams differ over whether to use the small-cell or the non-small-cell backbone.
A platinum doublet, with the choice between the small-cell and the non-small-cell backbone made case by case; the parent and the small-cell page carry the regimens.
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Query for this cancer: (TITLE:"Large cell neuroendocrine carcinoma of the lung" OR ABSTRACT:"Large cell neuroendocrine carcinoma of the lung" OR TITLE:"Pulmonary large cell neuroendocrine carcinoma" OR ABSTRACT:"Pulmonary large cell neuroendocrine carcinoma" OR TITLE:"LCNEC" OR ABSTRACT:"LCNEC" OR TITLE:"Large-cell neuroendocrine carcinoma" OR ABSTRACT:"Large-cell neuroendocrine carcinoma" OR TITLE:"Large cell neuroendocrine carcinoma a WHO 2021 lung neuroendocrine carcinoma, between small-cell and non-small-cell disease" OR ABSTRACT:"Large cell neuroendocrine carcinoma a WHO 2021 lung neuroendocrine carcinoma, between small-cell and non-small-cell disease" OR TITLE:"High-grade pulmonary neuroendocrine carcinoma, non-small-cell type" OR ABSTRACT:"High-grade pulmonary neuroendocrine carcinoma, non-small-cell type") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Large cell neuroendocrine carcinoma of the lung, not a curated reading list.
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