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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.
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.
How 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.
How 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.
Treatment: 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).
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).
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, 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
Treated as lung adenocarcinoma: non-squamous chemotherapy with pembrolizumab, driver testing, and the parent's stage-based pathway.
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Query for this cancer: (TITLE:"Large cell carcinoma of the lung" OR ABSTRACT:"Large cell carcinoma of the lung" OR TITLE:"Large-cell lung carcinoma" OR ABSTRACT:"Large-cell lung carcinoma" OR TITLE:"Large cell lung carcinoma" OR ABSTRACT:"Large cell lung carcinoma" OR TITLE:"Large-cell carcinoma" OR ABSTRACT:"Large-cell carcinoma" OR TITLE:"Large-cell / NOS" OR ABSTRACT:"Large-cell / NOS" OR TITLE:"Large cell lung carcinoma with rhabdoid phenotype variant retired in 2015" OR ABSTRACT:"Large cell lung carcinoma with rhabdoid phenotype variant retired in 2015") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Large cell carcinoma of the lung, not a curated reading list.
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Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Not recommended for CrCl below 45.
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
See all on the product pages:PembrolizumabPemetrexed·Printable cards in the navigator
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