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 such as smoking, 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 due to chronic disease of the lung. Likewise, changes in the tissue of the nail beds, known as clubbing, also may indicate chronic 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 small 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 mimic lung cancer.



• CT (computerized tomography, computerized axial tomography, or CAT) scans may be performed on the chest, abdomen, and/or brain to examine for both metastatic and lung tumors. A CT scan of the chest may be ordered when X-rays do not show an abnormality 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, that is, they will demonstrate more nodules. Sometimes intravenous contrast material is given prior to the scan 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. This may result in 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 CT 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 appropriate 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 drugs to produce three-dimensional colored images of those substances in the tissues within the body. While CT scans and MRI scans look at anatomical structures, PET scans measure metabolic activity and the function of tissues. 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, receiving approximately the amount of radiation exposure as two chest X-rays. The drug accumulates in certain tissues more than others, depending on the drug that is injected. The drug discharges particles known as positrons from whatever tissues take them up. 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 radioactive drug has accumulated. For example, combining glucose (a common energy source in the body) with a radioactive substance will show where glucose is rapidly being used, for example, 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, fiberoptic probe inserted through the nose or mouth) may reveal areas of tumor that can be sampled (biopsied) for diagnosis by a pathologist. 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 it requires sedation or anesthesia. While bronchoscopy is relatively safe, it 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 usually is possible. Some patients may cough up dark-brown blood for one to two days after the procedure. More serious but 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 that may contain metastases) or thoracotomy (surgical opening of the chest wall for removal or biopsy of a tumor). With a thoracotomy, it is rare to be 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 tumor metastatic to the liver. One current focus of research in the area of lung cancer is the development of a blood test to aid in the diagnosis of lung cancer. Researchers have preliminary data that has identified specific proteins, or biomarkers, that are in the blood and may signal that lung cancer is present in someone with a suspicious area seen on a chest X-ray or other imaging study.

Schematic illustration of a lung cancer located in the right upper lobe of the lung.