Pathogenesis It most often arises centrally in larger bronchi, and while it often metastasizes to locoregional lymph nodes (particularly the hilar nodes) early in its course, it generally disseminates outside the thorax somewhat later than other major types of lung cancer. Large tumors may undergo central necrosis, resulting in cavitation. A<unk> -cell carcinoma is often preceded for years by<unk> -cell metaplasia or dysplasia in the respiratory epithelium of the bronchi, which later transforms to carcinoma in situ. Large scale studies such as The Cancer Genome Atlas (TCGA) have systematically characterized recurrent somatic alterations likely driving lung<unk> -cell carcinoma initiation and development. Gene mutations and copy number alterations<unk> -cell lung carcinoma is one of the tumor types with the highest number of mutations since smoking, the main driver of the disease, is a strong mutagenic factor. Inactivating mutations in lung SCC affect many tumor suppressor genes such as TP53 (mutated in 81% of cases), MLL2 (20%), CDKN2A (15%), KEAP1 (12%) and PTEN (8%). Recurrent loss-of-function mutations have been observed also in NOTCH1 (8%), suggesting a tumor suppressive role in lung SCC for this gene, that has also been implicated as an oncogene in haematological cancers. On the other hand, recurrent gain-of-function mutations have been found in oncogenes such as PIK3CA (16%) and NFE2L2 (15%). Common oncogene copy number amplifications have been found in SOX2, PDGFRA, EGFR, FGFR1 and CCND1. Deletions were observed in tumor suppressors such as CDKN2A, PTEN and NF1. Some alterations such as the ones affecting TP53 and CDKN2A are shared by lung SCC and the other most common type of NSCLC, lung adenocarcinoma. Conversely, the two main driver oncogenes of the latter, EGFR and KRAS, are rarely mutated in lung SCC. Somatically altered pathways Many of the gene mutations and copy number alterations occur in pathways whose deregulation seems to be important for the initiation and progression of the tumor. Specifically, KEAP1 and NFE2L2 belong to the oxidative stress response pathways; alterations in these genes tend to occur in a mutually exclusive fashion, and therefore this pathway is overall altered in more than 30% of the cases. Similarly, the<unk>  cell differentiation pathway, whose components include SOX2, TP63 and NOTCH1, is altered in 44% of the tumors. Alterations in the receptor tyrosine kinase pathway are also common but not as widespread as for the adenocarcinoma type. RNA expression profiles Recently, four mRNA expression subtypes (primitive, basal, secretory, and classical) were identified and validated within<unk> -cell carcinoma. The primitive subtype correlates with worse patient survival. These subtypes, defined by intrinsic expression differences, provide a possible foundation for improved patient prognosis and research into individualized therapies.
Squamous-cell carcinoma of the lung
Sarcomatoid carcinoma of the lung
Adenocarcinoma of the lung
Giant-cell carcinoma of the lung
Pulmonary sclerosing pneumocytoma
Acinic cell carcinoma of the lung
Non-small-cell lung carcinoma
Large-cell lung carcinoma