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Lung cancer has been more frequently observed during the last 70 years. Many factors thought to be of pathogenic importance in the past are now considered to be totally unrelated or minimally related to cancer. The exposure to asbestosis, polycyclic aromatic hydrocarbons, nickel, arsenic, radon, and vinyl chloride are also responsible for carcinomas. But all of these factors become extremely unimportant when compared with the role played by smoking. Tobacco has a long history dating back to 600 A.D. It is known that Native Americans smoked tobacco for special religious and medical purposes. In 1964, the first report was published about the dangers of smoking and it was noticed that the nicotine and tar in cigarettes cause lung cancer. It is currently known that the smoke contains high levels of carcinogenic tobacco-specific nitrosamines. Therefore lung tumors that are histologically similar to the smoking-related lung cancers in humans do not develop in "non-smoker" animals. Most cases of lung cancer are most frequently diagnosed at an advanced stage where only limited number of treatment alternatives can be offered to these patients. The development of lung cancer involves multiple phases of tumorigenesis including interactions among genetic, epigenetic, and environmental factors with resultant dysregulation of key oncogenes and tumor suppressor genes ending in activation of cancer-related signaling pathways. For years, lung cancers have been classified as small cell and non-small cell lung cancers and this classification was satisfactory for treatment. The past decade has witnessed the discovery of multiple molecules that are effective in the development of lung cancer which are more commonly detected in adenocarcinomas. Therefore in histopathological examination, special aim is placed on discriminating adenocarcinomas from the other lung cancers so as to effectively select tumors for targeted molecular testing. Current review summarizes the histopathological features of lung cancers according to the 2015 World Health Organization (WHO) classification of lung cancer and attempts to focus on further understanding of the molecular abnormalities underlying lung cancer development and progression.

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