Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung , derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and women, is responsible for 1.3 million deaths worldwide annually. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.

The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma . This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation. The most common cause of lung cancer is long-term exposure to tobacco smoke. The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases , is often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution, including secondhand smoke.

Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Depending on the stage and treatment, the five-year survival rate is 14%.

Classification

The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. There are two main types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80.4%) and small-cell (16.8%) lung carcinoma. This classification, based on histological criteria, has important implications for clinical management and prognosis of the disease.

Non-small cell lung carcinoma (NSCLC)

The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large cell lung carcinoma.

Accounting for 25% of lung cancers, squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.

Adenocarcinoma accounts for 40% of lung cancers. It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.

Small cell lung carcinoma (SCLC)

Small cell lung carcinoma (SCLC, also called "oat cell carcinoma") is less common. It tends to arise in the larger airways (primary and secondary bronchi) and grows rapidly, becoming quite large. The "oat" cell contains dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this an endocrine/paraneoplastic syndrome association. While initially more sensitive to chemotherapy, it ultimately carries a worse prognosis and is often metastatic at presentation. Small cell lung cancers are divided into limited stage and extensive stage disease. This type of lung cancer is strongly associated with smoking.

Others

In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.

Secondary cancers

The lung is a common place for metastasis from tumors in other parts of the body. These secondary cancers are identified by the site of origin; thus, a breast cancer metastasis to the lung is still known as breast cancer. They often have a characteristic round appearance on chest radiograph. In children, the majority of lung cancers are secondary.

Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.

Staging

See also: Lung cancer staging

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis). Small cell lung carcinoma is classified as limited stage if it is confined to one half of the chest and within the scope of a single radiotherapy field; otherwise, it is extensive stage .

Signs and symptoms

Symptoms that suggest lung cancer include:

  • dyspnea (shortness of breath)
  • hemoptysis (coughing up blood)
  • chronic coughing or change in regular coughing pattern
  • wheezing
  • chest pain or pain in the abdomen
  • cachexia (weight loss), fatigue, and loss of appetite
  • dysphonia (hoarse voice)
  • clubbing of the fingernails (uncommon)
  • dysphagia (difficulty swallowing).

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.

Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus.

Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.

Causes

The main causes of lung cancer (and cancer in general) include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.

Smoking

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer. Across the developed world, almost 90% of lung cancer deaths are caused by smoking. In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women). Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women. Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.

The length of time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed. In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers, and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.

Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker as well. Studies from the U.S., Europe, the UK, and Australia have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation.

Roughly ten-fifteen percent of lung cancer patients have never smoked. That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United

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