[Large cell carcinoma, lymphoepithelioma-like carcinoma, NUT carcinoma]

The diagnosis of large cell carcinoma can only be made on a sampled resected tumor and should not be applied to biopsies or cytology. In the 2015 WHO classification, the definition of large cell carcinoma is restricted to carcinomas both lacking morphological signs of glandular, squamous or neuroendocrine differentiation and exhibiting a null or unclear phenotype (TTF1-/p40 ou p63 ou CK5/6+ focally). These carcinomas have an adenocarcinoma molecular profile because they harbor a significant number of KRAS and BRAF mutations, a profile that is more similar to adenocarcinoma than squamous cell carcinoma. They also have a worse prognosis than the other types of non-small cell lung carcinoma. Many large cell carcinomas previously classified on morphological data alone are now reclassified in the adenocarcinoma and squamous cell carcinoma types, including immunohistochemical features. The other large cell carcinoma subtypes from the 2004 WHO classification, i.e. large cell neuroendocrine carcinoma and basaloid carcinoma, are grouped respectively with the other neuroendocrine tumors and squamous cell carcinomas. Clear cell and rhabdoid features are now considered as cytological variants that can occur in any histopathological subtype and not as distinct subtypes. Lymphoepithelioma-like carcinoma is moved to the group of other and unclassified carcinomas as NUT carcinoma.