{"entity":{"id":"large-cell-lung-carcinoma","kind":"cancer","name":"Large cell carcinoma of the lung","aka":["Large-cell lung carcinoma","Large cell lung carcinoma","Large-cell carcinoma","Large-cell / NOS","Large cell lung carcinoma with rhabdoid phenotype (variant retired in 2015)","Undifferentiated non-small-cell lung cancer"],"tldr":"Large cell carcinoma is the name for a non-small-cell lung cancer whose cells look neither glandular nor squamous under the microscope. Since 2015 pathologists use protein stains to sort most of these tumours into adenocarcinoma or squamous cell carcinoma, so a true large cell diagnosis is now rare and is treated like adenocarcinoma.","summary":"The WHO classification defines large cell carcinoma as an undifferentiated non-small-cell carcinoma that lacks the cytological, architectural and immunohistochemical features of small cell carcinoma, adenocarcinoma or squamous cell carcinoma; since 2015 the diagnosis can be made only on a resection specimen after immunohistochemistry (TTF-1, napsin A, p40, p63, neuroendocrine markers) is negative or inconclusive (Travis 2015). In a study of 121 tumours across the historical spectrum of large cell carcinoma, all 47 large cell neuroendocrine carcinomas showed neuroendocrine lineage, all 24 basaloid and both lymphoepithelioma-like carcinomas showed squamous markers, and 18 of 22 clear cell carcinomas had glandular differentiation with KRAS mutations in 39 percent (Pelosi 2014); tumours with no marker at all are clinically and genomically indistinguishable from solid adenocarcinoma (Rekhtman 2014). Large cell neuroendocrine carcinoma is now classified with the neuroendocrine neoplasms.\n\nHow it differs from its parent: this is a diagnosis of exclusion within non-small-cell lung cancer rather than a lineage. Its former variants (clear cell, rhabdoid, basaloid, lymphoepithelioma-like) were reassigned in 2015, and the rhabdoid phenotype no longer exists as a category.\n\nHow common: about 10 percent of lung cancers in the PDQ figure, which predates the reclassification; no current registry figure for the narrowed category was found in the sources read.\n\nTreatment: no trial has enrolled large cell carcinoma alone. Guidelines and the PDQ summary treat it with non-squamous (adenocarcinoma) regimens, including pemetrexed-based chemotherapy with pembrolizumab, and recommend the same driver testing as adenocarcinoma because null-immunophenotype tumours carry adenocarcinoma-type alterations (Rekhtman 2014).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Large-cell_lung_carcinoma","links":[{"label":"NCI PDQ (health professional): non-small cell lung cancer treatment, histological shares","url":"https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq"},{"label":"Travis 2015, JTO: the 2015 WHO classification of lung tumours","url":"https://doi.org/10.1097/jto.0000000000000630"},{"label":"Pelosi 2014, Virchows Archiv: large cell carcinoma of the lung reclassified by immunohistochemistry and molecular biology","url":"https://doi.org/10.1007/s00428-013-1501-6"},{"label":"Rekhtman 2014, Curr Opin Pulm Med: large cell carcinoma redefined by immunohistochemistry and genomics","url":"https://doi.org/10.1097/mcp.0000000000000068"}],"tags":["subtype-page","wave4","lung"],"related":["nsclc","lung-adenocarcinoma","lung-squamous-cell-carcinoma","pulmonary-sarcomatoid-carcinoma","lung-net"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pemetrexed","pembrolizumab","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"lung","burden":"About 10 percent of lung cancers in the NCI PDQ figures, but the category has shrunk since 2015 because most tumours once called large cell are reassigned to adenocarcinoma or squamous cell carcinoma by immunohistochemistry (Travis 2015).","subtypes":["Large cell carcinoma, null immunophenotype (treated as solid adenocarcinoma)","Large cell carcinoma with unclear staining (TTF-1 and p40 both weak or focal)","Former variants reassigned in 2015: clear cell (to adenocarcinoma), basaloid and lymphoepithelioma-like (to squamous), large cell neuroendocrine carcinoma (to neuroendocrine)"],"biomarkers":["Negative or inconclusive TTF-1, napsin A, p40 and p63","Neuroendocrine markers negative (otherwise large cell neuroendocrine carcinoma)","Driver testing as for adenocarcinoma (KRAS most often)","PD-L1"],"standardOfCare":[{"setting":"All stages","approach":"Treated as lung adenocarcinoma: non-squamous chemotherapy with pembrolizumab, driver testing, and the parent's stage-based pathway.","refs":["lung-adenocarcinoma","pemetrexed","pembrolizumab","nsclc"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"nsclc"},"route":"/cancers/large-cell-lung-carcinoma/","neighbours":{"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"basaloid-squamous-cell-carcinoma-lung","kind":"cancer","name":"Basaloid squamous cell carcinoma of the lung","route":"/cancers/basaloid-squamous-cell-carcinoma-lung/"},{"id":"lung-net","kind":"cancer","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","route":"/cancers/lung-net/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pulmonary-sarcomatoid-carcinoma","kind":"cancer","name":"Sarcomatoid carcinoma of the lung","route":"/cancers/pulmonary-sarcomatoid-carcinoma/"},{"id":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","route":"/cancers/lung-squamous-cell-carcinoma/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}]}}