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A 75-year-old woman comes to the emergency department because of a severe headache and double vision for a day. She says she has recently also fallen several times because she feels unsteady when she is walking. She denies neck stiffness or pain. She has a history of lung cancer that recurred last year and was complicated by liver metastases. Examination shows that her voice sounds hoarse. She is afebrile, but drowsy. She is able to follow commands and is able to move all four of her extremities. Pupils are 4 mm bilaterally. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
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 it has contributed to the deaths of millions of people including famous individuals like Walt Disney and Claude Monet.
Each bronchi enters its respective lung at the hilum, or root of the lung.
The bronchi then divides into lobar bronchi, which divide into segmental bronchi, 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 occurs.
Lining these airways are several types of epithelial cells which serve multiple functions.
These include ciliated cells that have hair-like project 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, 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 - the lining of the lungs, heart, breasts, liver, adrenal glands, brain, and bones.
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.
In general, they 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 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 is called a paraneoplastic syndrome.
One example is when the tumor releases adrenocorticotropic hormone causing an increase in production and release of cortisol from the adrenal glands. This causes what’s known as Cushing’s syndrome which causes a number of symptoms including an elevated blood glucose and high blood pressure.
A slightly different type of paraneoplastic syndrome, is when small cell carcinoma prompts the body to produce autoantibodies 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.
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