Lung Cancer

What is cancer of the lung?
Cancer of the lung, like all cancers, results from an abnormality in the body's basic unit of life, the cell. Normally, the body maintains a system of checks and balances on cell growth so that cells divide to produce new cells only when needed. Disruption of this system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor.
Tumors can be benign or malignant; when we speak of "cancer," we refer to those tumors that are considered malignant. Benign tumors can usually be removed and do not spread to other parts of the body. Malignant tumors, on the other hand, grow aggressively and invade other tissues of the body, allowing entry of tumor cells into the bloodstream or lymphatic system which spread the tumor to other sites in the body. This process of spread is termed metastasis; the areas of tumor growth at these distant sites are called metastases. Since lung cancer tends to spread, or metastasize, very early in its course, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs—particularly the adrenal glands, liver, brain, and bone—are the most common sites for lung cancer metastasis.
The lung is also a very common site for metastasis from tumors in other parts of the body. Tumor metastases are made up of the same type of cells as the original, or primary, tumor. For example, if prostate cancer spreads via the bloodstream to the lungs, it is metastatic prostate cancer in the lung and is not lung cancer.The principal function of the lungs is the exchange of gases between the air we breathe and the blood. Through the lung, carbon dioxide is removed from the body and oxygen from inspired air enters the bloodstream. The right lung has three lobes, while the left lung is divided into two lobes and a small structure called the lingula that is the equivalent of the middle lobe. The major airways entering the lungs are the bronchi, which arise from the trachea. The bronchi branch into progressively smaller airways called bronchioles that end in tiny sacs known as alveoli, where gas exchange occurs. The lungs and chest wall are covered with a thin layer of tissue called the pleura.
Lung cancers can arise in any part of the lung, and 90%-95% of cancers of the lung are thought to arise from the epithelial, or lining cells of the larger and smaller airways (bronchi and bronchioles); for this reason, lung cancers are sometimes called bronchogenic carcinomas or bronchogenic cancers. Cancers can also arise from the pleura (the thin layer of tissue that surrounds the lungs), called mesotheliomas, or rarely from supporting tissues within the lungs, for example, blood vessels.
How common is lung cancer?
Lung cancer is responsible for the most cancer deaths in both men and women throughout the world. The American Cancer Society estimates that 213,380 new cases of lung cancer in the U.S. will be diagnosed and 160,390 deaths due to lung cancer will occur in 2007. Lung cancer is predominantly a disease of the elderly; almost 70% of people diagnosed with the condition are over 65 years of age, while less than 3% of cases occur in people under age 45.
Lung cancer was not common prior to the 1930s but increased dramatically over the following decades as tobacco smoking increased. In many developing countries, the incidence of lung cancer is beginning to fall following public education about the dangers of cigarette smoking and effective smoking-cessation programs. Nevertheless, lung cancer remains among the most common types of cancers in both men and women worldwide.
Lung cancer has also surpassed breast cancer in causing the most cancer-related deaths in women in the United States.

What causes lung cancer?
Smoking
The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked over time; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history. While the risk of lung cancer is increased with even a 10 pack-year smoking history, those with 30 pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.
Pipe and cigar smoking can also cause lung cancer, although the risk is not as high as with cigarette smoking. While someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.
Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing, or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking. For more, please read the Smoking and Quitting Smoking article.
Passive smoking
Passive smoking, or the inhalation of tobacco smoke from other smokers sharing living or working quarters, is also an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with other nonsmokers. An estimated 3,000 lung cancer deaths occur each year in the U.S. that are attributable to passive smoking.
Asbestos fibers
Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past for both thermal and acoustic insulation materials. Today, asbestos use is limited or banned in many countries, including the Unites States. Both lung cancer and mesothelioma (a type of cancer of the pleura or of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos. Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in exposed workers. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, and those asbestos workers who smoke have a risk that is 50 to 90 times greater than nonsmokers.
Radon gas
Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. It decays to form products that emit a type of ionizing radiation. Radon gas is a known cause of lung cancer, with an estimated 12% of lung cancer deaths attributable to radon gas, or 15,000 to 22,000 lung cancer-related deaths annually in the U.S., making radon the second leading cause of lung cancer in the U.S. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings. The U.S. Environmental Protection Agency estimates that one out of every 15 homes in the U.S. contains dangerous levels of radon gas. Radon gas is invisible and odorless, but it can be detected with simple test kits.
Familial predisposition
While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and nonsmoking relatives of those who have had lung cancer than in the general population. Recent research has localized a region on the long (q) arm of the human chromosome number 6 that is likely to contain a gene that confers an increased susceptibility to the development of lung cancer in smokers.
Lung diseases
The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with a slightly increased risk (four to six times the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.
Prior history of lung cancer
Survivors of lung cancer have a greater risk than the general population of developing a second lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs), the risk for development of second cancers approaches 6% per year.
Air pollution
Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk similar to that of passive smoking for the development of lung cancer.
What are the types of lung cancer?
Lung cancers, also known as bronchogenic carcinomas ("carcinoma" is another term for cancer), are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways, so a distinction between these two types is important.
SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking, with only 1% of these tumors occurring in nonsmokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell type often seen in SCLC, these cancers are sometimes called oat cell carcinomas.
NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC has three main types that are named based upon the type of cells found in the tumor:
Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC . While adenocarcinomas are associated with smoking like other lung cancers, this type is especially observed as well in nonsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.
Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi.
Large cell carcinomas, sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC.
Mixtures of different types of NSCLC are also seen.
Other types of cancers can arise in the lung; these types are much less common than NSCLC and SCLC and together comprise only 5%-10% of lung cancers:
Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3-4 cm or less) when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection.
Cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response can rarely occur in the lung.
As discussed previously, metastastatic cancers from other primary tumors in the body are often found in the lung. Tumors from anywhere in the body may spread to the lungs either through the bloodstream, through the lymphatic system, or directly from nearby organs. Metastatic tumors are most often multiple, scattered throughout the lung, and concentrated in the peripheral rather than central areas of the organ.
What are the signs and symptoms of lung cancer?
Symptoms of lung cancer are varied dependent upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. A person with lung cancer may have the following kinds of symptoms:
No symptoms: In up to 25% of people who get lung cancer, the cancer is first discovered on a routine chest x-ray or CT scan as a solitary small mass sometimes called a coin lesion. These patients with small single masses often report no symptoms of lung cancer at the time it is discovered.
Symptoms related to the cancer: The growth of the cancer and invasion of lung tissues and surroundings may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder pain that travels down the outside of the arm (called Pancoast's Syndrome) or paralysis of the vocal cords leading to hoarseness. Invasion of the esophagus may lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses, pneumonia) in the obstructed area.
Symptoms related to metastasis: Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may include blurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.
Paraneoplastic symptoms: Lung cancers frequently are accompanied by so-called paraneoplastic syndromes that result from production of hormone-like substances by the tumor cells. Paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type. A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing's syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.
Nonspecific symptoms: Nonspecific symptoms seen with many cancers including lung cancers include weight loss, weakness, and fatigue. Psychological symptoms such as depression and mood changes are also common.
When should one consult a doctor?
One should consult a health care provider if they develop the symptoms associated with lung cancer, in particular, if they have
a new persistent cough or worsening of an existing chronic cough,
blood in the sputum,
persistent bronchitis or repeated respiratory infections,
chest pain,
unexplained weight loss and/or fatigue, and/or
breathing difficulties such as shortness of breath or wheezing.
How is lung cancer diagnosed?
Doctors use a wide range of diagnostic procedures and tests to diagnose lung cancer. These include:
The history and physical examination may reveal the presence of symptoms or signs that are suspicious for lung cancer. In addition to asking about symptoms and risk factors for cancer development, doctors may detect signs of breathing difficulties, airway obstruction, or infections in the lungs. Cyanosis, a bluish color of the skin and the mucous membranes due to insufficient oxygen in the blood, suggests compromised function of the lung. Likewise, changes in the tissue of the nail beds, known as clubbing, may also indicate lung disease.
The chest x-ray is the most common first diagnostic step when any new symptoms of lung cancer are present. The chest x-ray procedure often involves a view from the back to the front of the chest as well as a view from the side. Like any x-ray procedure, chest x-rays expose the patient briefly to a minimum amount of radiation. Chest x-rays may reveal suspicious areas in the lungs but are unable to determine if these areas are cancerous. In particular, calcified nodules in the lungs or benign tumors called hamartomas may be identified on a chest x-ray and simulate lung cancer.
CT (computerized axial tomography scan, or CAT scan) scans may be performed on the chest, abdomen, and/or brain to examine for both metastatic and primary tumor. A CT scan of the chest may be ordered when x-rays are negative or do not yield sufficient information about the extent or location of a tumor. CT scans are x-ray procedures that combine multiple images with the aid of a computer to generate cross-sectional views of the body. The images are taken by a large donut-shaped x-ray machine at different angles around the body. One advantage of CT scans is that they are more sensitive than standard chest x-rays in the detection of lung nodules. Sometimes intravenous contrast material is given prior to the procedure to help delineate the organs and their positions. A CT scan exposes the patient to a minimal amount of radiation. The most common side effect is an adverse reaction to intravenous contrast material that may have been given prior to the procedure. There may be resulting itching, a rash, or hives that generally disappear rather quickly. Severe anaphylactic reactions (life-threatening allergic reactions with breathing difficulties) to contrast material are rare. CT scans of the abdomen may identify metastatic cancer in the liver or adrenal glands, and CT scans of the head may be ordered to reveal the presence and extent of metastatic cancer in the brain.
A technique called a low-dose helical CT scan (or spiral CT scan) is sometimes used in screening for lung cancers. This procedure requires a special type of CAT scanner and has been shown to be an effective tool for the identification of small lung cancers in smokers and former smokers. However, it has not yet been proven whether the use of this technique actually saves lives or lowers the risk of death from lung cancer. The heightened sensitivity of this method is actually one of the sources of its drawbacks, since lung nodules requiring further evaluation will be seen in approximately 20% of people with this technique. Of the nodules identified by low-dose helical screening CTs, 90% are not cancerous but require up to two years of costly and often uncomfortable follow-up and testing. Trials are underway to further determine the utility of spiral CT scans in screening for lung cancer.
Magnetic resonance imaging (MRI) scans may be indicated when precise detail about a tumor's location is required. The MRI technique uses magnetism, radio waves, and a computer to produce images of body structures. As with CT scanning, the patient is placed on a moveable bed which is inserted into the MRI scanner. There are no known side effects of MRI scanning, and there is no exposure to radiation. The image and resolution produced by MRI is quite detailed and can detect tiny changes of structures within the body. People with heart pacemakers, metal implants, artificial heart valves, and other surgically implanted structures cannot be scanned with an MRI because of the risk that the magnet may move the metal parts of these structures.
Positron emission tomography (PET) scanning is a specialized imaging technique that uses short-lived radioactive substances to produce three-dimensional colored images of those substances functioning within the body. While CT scans and MRI scans look at anatomical structures, PET scans measure metabolic activity and functioning of tissue. PET scans can determine whether a tumor tissue is actively growing and can aid in determining the type of cells within a particular tumor. In PET scanning, the patient receives a short half-lived radioactive drug and receives approximately the amount of radiation exposure as with two chest x-rays. The drug discharges positrons from wherever they are used in the body. As the positrons encounter electrons within the body, a reaction producing gamma rays occurs. A scanner records these gamma rays and maps the area where the drug is located. For example, combining glucose (a common energy source in the body) with a radioactive substance will show where glucose is being used in a growing tumor.
Bone scans are used to create images of bones on a computer screen or on film. Doctors may order a bone scan to determine whether a lung cancer has metastasized to the bones. In a bone scan, a small amount of radioactive material is injected into the bloodstream and collects in the bones, especially in abnormal areas such as those involved by metastatic tumors. The radioactive material is detected by a scanner, and the image of the bones is recorded on a special film for permanent viewing.
Sputum cytology: The diagnosis of lung cancer always requires confirmation of malignant cells by a pathologist, even when symptoms and x-ray studies are suspicious for lung cancer. The simplest method to establish the diagnosis is the examination of sputum under a microscope. If a tumor is centrally located and has invaded the airways, this procedure, known as a sputum cytology examination, may allow visualization of tumor cells for diagnosis. This is the most risk-free and inexpensive tissue diagnostic procedure, but its value is limited since tumor cells will not always be present in sputum even if a cancer is present. Also, noncancerous cells may occasionally undergo changes in reaction to inflammation or injury that makes them look like cancer cells.
Bronchoscopy: Examination of the airways by bronchoscopy (visualizing the airways through a thin probe inserted in a tube through the nose or mouth) may reveal areas of tumor that can be sampled for pathologic diagnosis. A tumor in the central areas of the lung or arising from the larger airways is accessible to sampling using this technique. Bronchoscopy may be performed using a rigid or a flexible, fiberoptic bronchoscope and can be performed in a same-day outpatient bronchoscopy suite, an operating room, or on a hospital ward. The procedure can be uncomfortable and require sedation or anesthesia. While the procedure is relatively safe, the procedure must be carried out by a lung specialist (pulmonologist or surgeon) experienced in the procedure. When a tumor is visualized and adequately sampled, an accurate cancer diagnosis is generally possible. Some patients may cough up dark-brown blood for one to two days after the procedure. More serious, and rare, complications include a greater amount of bleeding, decreased levels of oxygen in the blood, and heart arrhythmias as well as complications from sedative medications and anesthesia.
Needle biopsy: Fine needle aspiration (FNA) through the skin, most commonly performed with radiological imaging for guidance, may be useful in retrieving cells for diagnosis from tumor nodules in the lungs. Needle biopsies are particularly useful when the lung tumor is peripherally located in the lung and not accessible to sampling by bronchoscopy. A small amount of local anesthetic is given prior to insertion of a thin needle through the chest wall into the abnormal area in the lung. Cells are suctioned into the syringe and are examined under the microscope for tumor cells. This procedure is generally accurate when the tissue from the affected area is adequately sampled, but in some cases, adjacent or uninvolved areas of the lung may be mistakenly sampled. A small risk (3%-5%) of an air leak from the lungs (called a pneumothorax, which can easily be treated) accompanies the procedure.
Thoracentesis: Sometimes lung cancers involve the lining tissue of the lungs (pleura) and lead to an accumulation of fluid in the space between the lungs and chest wall (called a pleural effusion). Aspiration of a sample of this fluid with a thin needle (thoracentesis) may reveal the cancer cells and establish the diagnosis. As with the needle biopsy, a small risk of a pneumothorax is associated with this procedure.
Major surgical procedures: If none of the aforementioned methods yields a diagnosis, surgical methods must be employed to obtain tumor tissue for diagnosis. These can include mediastinoscopy (examining the chest cavity between the lungs through a surgically inserted probe with biopsy of tumor masses or lymph nodes) or thoracotomy (surgical opening of the chest wall with removal of as much tumor as possible). Thoracotomy is rarely able to completely remove a lung cancer, and both mediastinoscopy and thoracotomy carry the risks of major surgical procedures (complications such as bleeding, infection, and risks from anesthesia and medications). These procedures are performed in an operating room, and the patient must be hospitalized.
Blood tests: While routine blood tests alone cannot diagnose lung cancer, they may reveal biochemical or metabolic abnormalities in the body that accompany cancer. For example, elevated levels of calcium or of the enzyme alkaline phosphatase may accompany cancer that is metastatic to the bones. Likewise, elevated levels of certain enzymes normally present within liver cells, including aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), signal liver damage, possibly through the presence of metastatic tumor.