Lung cancer is a disease where tissue in the lung grows out of control. This leads to invasion of adjacent tissue and infiltration beyond the lungs (metastasis).

Lung cancer, the most common cause of cancer-related death in men and the second most common in women, is responsible for 1.3 million deaths worldwide annually. The most common symptoms are shortness of breath, cough (including coughing up blood), and weight loss.

 The main types of lung cancer are small cell lung cancer and non-small cell lung cancer. This distinction is important because non-small cell lung cancer is sometimes curable with surgery, while small cell cancer is not. Also, small cell lung cancer usually responds better to chemotherapy.

 The most significant risk factor for developing lung cancer is long-term exposure to inhaled carcinogens, especially tobacco smoke. The occurrence of lung cancer in non-smokers, who account for less than 10% of cases, appears to be due to a combination of genetic factors. Radon gas, asbestos, and air pollution may also contribute to the development of lung cancer.

 Lung cancer is often seen on chest x-ray and 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. Even with treatment, the overall five-year survival rate is 14%.

Classification

 Types

 There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80%) and small-cell (roughly 20%) lung cancer. This classification, although based on simple histological criteria, has very important implications for clinical management and prognosis of the disease.

 Non-small cell lung cancer (NSCLC)

 The non-small cell lung cancers are grouped together because their prognosis and management are roughly identical. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma. When NSCLC cannot be subtyped, it is assigned SNOMED code 8046/3.

 Squamous cell lung carcinoma, accounting for 29% of lung cancers, usually starts near a central bronchus. Cavitation and necrosis within the center of the cancer is a common finding. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.

 Adenocarcinoma is the most common subtype of NSCLC, accounting for 32% 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.

 Large cell carcinoma is a fast-growing form, accounting for 9% of lung cancers, that grows near the surface of the lung. It is often poorly differentiated and tends to metastasize early.

 Small cell lung cancer (SCLC)

 Small cell lung cancer (SCLC, also called "oat cell carcinoma") is the less common form of lung cancer. It tends to start in the larger breathing tubes and grows rapidly becoming quite large. The oncogene most commonly involved is L-myc. The "oat" cell contains dense neurosecretory granules which give this an endocrine/paraneoplastic syndrome association. It is initially more sensitive to chemotherapy, but ultimately carries a worse prognosis and is often metastatic at presentation. This type of lung cancer is strongly associated with smoking.

 

Other types

 Rarer forms of lung cancer include carcinoid, adenoid cystic carcinoma (cylindroma) and mucoepidermoid carcinoma.

 Metastatic cancers

 The lung is a common place for metastasis from tumors in other parts of the body. These cancers, however, are identified by the site of origin, e.g. a breast cancer metastasis to the lung is still known as breast cancer. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer itself.

 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 cancer is staged from IA ("one A", best prognosis) to IV ("four", worst prognosis). Small cell lung cancer 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)

    * 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 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.

 Unfortunately, many of the symptoms of lung cancer (bone pain, fever, 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 bone, such as the spine (causing back pain and occasionally spinal cord compression), the liver and the brain. About 10% of people with lung cancer do not have symptoms of it at the time of diagnosis; these cancers are usually found on routine chest x-rays.

 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. 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 non-smokers: 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 continues to smoke as well as the amount smoked increases the person's chances of developing lung cancer. If a person stops smoking, these chances steadily decrease as damage to the lungs is repaired and contaminant particles are gradually vacated. More recent work has shown that, across the developed world, almost 90% of lung cancer deaths are caused by smoking. 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 than those who have quit.

  Asbestos

 Asbestos can cause a variety of lung diseases. It increases the risk of developing lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

 Radon gas

 Radon is a colorless and odourless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer after smoking.

 Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picoCuries per liter (pCi/L). Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk with prolonged radon exposure above the EPA's action level of 4 pCi/L.

 Viruses

 Viruses are known to cause lung cancer in animals and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus, JC virus, simian virus 40 (SV40), BK virus and cytomegalovirus.

 Pathophysiology

 Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Oncogenes are genes that are believed make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutations in the K-ras proto-oncogene are responsible for 20–30% of non-small cell lung cancers. Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q and 17p are particularly common in small cell lung carcinoma. The TP53 tumor suppressor gene, located on chromosome 17p, is often affected. 

Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in interleukin-1, cytochrome P450 and DNA repair molecules such as XRCC1. People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.

 Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (infection) and pleural effusion. If there are no X-ray findings but the suspicion is high (e.g. a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. In any case, bronchoscopy or CT-guided biopsy is often necessary to identify the tumor type.

 The differential diagnosis for patients who present with abnormalities on chest x-ray includes lung cancer, as well as other nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.

 

 

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