Lung cancer

Lung cancer, or lung carcinoma, is the uncontrolled division of epithelial cells which line the respiratory tract. There are two main categories of lung cancer: small cell and non-small cell which depend on the type of epithelial cell that’s dividing. Both types can be fatal, especially if the cancerous cells aggressively spread and establish secondary sites of cancer in other tissues. The major cause of lung cancer is smoking tobacco products, and has contributed to the deaths of millions of people, including famous individuals like Walt Disney and Claude Monet.

Now, air enters the respiratory tract through either the nose or mouth, and flows down the trachea, which divides into the right and left bronchi. Each bronchus enters its respective lung at the hilum, or the root of the lung. The bronchi then divides into lobar bronchi, which divide into segmental bronchi, and then into subsegmental bronchi which further branch to form conducting bronchioles, and then respiratory bronchioles which end with small sacs called alveoli that are surrounded by capillaries, which is where gas exchange happens.

Lining these airways are several types of epithelial cells which serve multiple functions. These include ciliated cells that have hairlike projections called cilia that work to sweep foreign particles and pathogens back to the throat to be swallowed. Another type called Goblet cells, which are called that because they look like goblets, secrete mucin to moisten the airways and trap foreign pathogens. There are also basal cells that are thought to be able to differentiate into other cells in the epithelium, club cells that act to protect the bronchiolar epithelium, and neuroendocrine cells that secrete hormones into the blood in response to neuronal signals.

Cells can become mutated because of environmental or genetic factors. A mutated cell becomes cancerous when it starts to divide uncontrollably. As cancer cells start piling up on each other, they become a small tumor mass, and they need to induce blood vessel growth, called angiogenesis, to supply themselves with energy. Malignant tumors are ones that are able to break through the basement membrane. Some of these malignant tumors go a step further and detach from their basement membrane at the primary tumor site, and then enter nearby blood vessels, and establish secondary sites of tumor growth throughout the body—a process called metastasis.

A well-known risk factor for small cell lung cancer and some types of non-small cell lung cancer is smoking tobacco and it’s dose-dependent, which means that smoking more cigarettes over a longer period of time increases the risk. Another risk factor is exposure to radon, a colorless, odorless gas which is a natural breakdown product of uranium found in the soil.

Other environmental factors include: asbestos; air pollution; and ionizing radiation, like from medical imaging with chest X-rays and CT scans. There are also some gene mutations that are known to be associated with an increased risk of lung cancer development. Once it develops, lung cancer tends to metastasize quickly, rapidly establishing sites of secondary tumors in other tissues. Tissues particularly at risk as a secondary site are the mediastinum and hilar lymph nodes because of their proximity to the lungs. But other sites include: the lung pleura, which is the lining of the lungs; as well as the heart; breasts; liver; adrenal glands; brain; and bones.

Lung cancer can be categorized as either small cell or non-small cell carcinomas. Small cell carcinomas account for a small portion of lung cancers and originate from small, immature neuroendocrine cells. That means that non-small cell carcinomas account for most lung cancers, and these can be further subdivided into four categories: adenocarcinomas, which frequently form glandular structures or have the ability to generate mucin; squamous cell carcinomas, which have squamous or square-shaped cells that produce keratin; carcinoid tumors from mature neuroendocrine cells; and large cell carcinomas which lack both glandular and squamous differentiation.

Small cell carcinomas are strongly associated with smoking, and usually develop centrally in the lung, near a main bronchus. In general, these grow the fastest and more rapidly metastasize to other organs than other types of non-small cell lung cancers. Because of this, by the time it’s diagnosed, it’s common to find large tumors in multiple locations both within and outside the lung. Typically, when a small cell carcinoma is within one lung, it’s considered limited. If it spreads beyond one lung, it’s considered extensive.

Small cell carcinomas can also sometimes secrete hormones and that can lead to what’s called a paraneoplastic syndrome. One example is when the tumor releases adrenocorticotropic hormone, causing an increase in production and the release of cortisol from the adrenal glands. This causes what’s known as Cushing’s syndrome, which causes a number of other symptoms, including an elevated blood glucose and high blood pressure.

Another example is when the tumor releases antidiuretic hormone which causes water retention leading to high blood pressure, edema, and concentrated urine. A slightly different type of paraneoplastic syndrome is when the small cell carcinoma prompts the body to produce auto-antibodies which bind and destroy neurons causing Lambert-Eaton myasthenic syndrome, which is a type II hypersensitivity reaction.

Non-small cell carcinomas are more of a mixed bag in terms of where they usually arise. Just like small cell carcinomas, squamous cell carcinoma tends to be centrally located, and has a strong association with smoking. Smoking also increases the risk of adenocarcinomas but they tend to develop peripherally, in a bronchiole or alveolar wall.

Large cell carcinomas and bronchial carcinoid tumors can be found throughout the lungs, centrally and peripherally. Of these two, large cell carcinoma has a stronger link to smoking. Both adenocarcinoma and squamous cell carcinoma can form Pancoast tumors, which are masses in the upper region of the lung that compress the blood vessels and nerves located there.