context: A solitary pulmonary nodule ( SPN) is a single abnormality in the lung that is smaller than 3 cm in diameter. Generally, a pulmonary nodule must grow to at least 1 cm in diameter before it can be seen on a chest X-ray. An SPN is surrounded by normal lung tissue and is not associated with any other abnormality in the lung or nearby lymph nodes (small, bean-shaped structures found throughout the body). People with SPNs usually do not experience symptoms. SPNs are usually noticed by chance on a chest X-ray that has been taken for another reason (referred to as an incidental finding). SPNs are a common abnormality seen on chest X-rays that often needs further evaluation. Approximately 150,000 cases are detected every year as incidental findings, either on X-rays or CT scans. Most SPNs are benign (noncancerous); however, they may represent an early stage of primary lung cancer or may indicate that cancer is metastasizing (spreading) from another part of the body to the affected lung. Determining whether the SPN seen on the chest X-ray or chest CT scan is benign or malignant (cancerous) is important. Prompt diagnosis and treatment of early lung cancer that looks like an SPN may be the only chance to cure the cancer. Solitary pulmonary nodules may have the following causes: Neoplastic (an abnormal growth that can be benign or malignant): Lung cancer Metastasis (spread of cancer from other parts of the body to the lung) Lymphoma (a tumor made up of lymphoid tissue) Carcinoid (a small, slow-growing tumor that can spread) Hamartoma (an abnormal mass of normal tissues that are poorly organized) Fibroma (a tumor made up of fibrous connective tissue) Neurofibroma (a noncancerous tumor made up of nerve fibers) Blastoma (a tumor composed mainly of immature, undifferentiated cells) Sarcoma (a tumor made up of connective tissue -- usually cancerous) Inflammatory (infectious) -- Granuloma (small, granular inflammatory lesions) Infection caused by bacteria -- Tuberculosis or nocardiosis Infections caused by fungi -- Histoplasmosis, coccidioidomycosis, blastomycosis, or cryptococcosis Other infectious causes: Lung abscess (an infection in which cells of a part of the lung die) Round pneumonia (infection caused by virus or bacteria; air spaces of the lungs are filled with fluid and cells) Hydatid cyst (a cyst formed by the larval stage of a tapeworm, Echinococcus) Inflammatory (noninfectious): Rheumatoid arthritis (a generalized disease of the connective tissues; joint pain is the main symptom) Granulomatosis with polyangiitis (inflammation of the small blood vessels characterized by lesions that kill the cells in different organs of the body) Sarcoidosis (a disease characterized by granular lesions of unknown cause that involves various organs of the body) Lipoid (resembling fat) pneumonia Congenital: Arteriovenous malformation (failure of proper or normal development of arteries and veins) Sequestration (a piece of lung tissue that has become separated from the surrounding healthy tissue) Lung cyst (an abnormal sac that contains gas, fluid, or a semisolid material) Miscellaneous: Pulmonary infarct (death of cells or of a portion of lung, resulting from a sudden insufficiency of blood supply) Round atelectasis (decreased or absent air in a part of the lung) Mucoid impaction (the filling of parts of the lung with mucus) Progressive massive fibrosis, also called "black lung disease" (formation of fibrous tissue as a reactive process, as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue) Occasionally, a shadow on the X-ray film may be mistaken for a SPN. Most persons with a SPN do not experience symptoms. Generally, a SPN is detected as an incidental finding. Lung cancer can often appear as an SPN on chest X-ray. Therefore, the goal of investigating an SPN is to differentiate a benign growth from a malignant growth as soon and as accurately as possible. SPNs should be considered potentially cancerous until proven otherwise. People should always communicate openly and honestly with their health care provider about their history and risk factors. The following features are important when assessing whether the SPN is benign or malignant. Age: Risk of malignancy increases with age. Risk of 3% at age 35-39 years Risk of 15% at age 40-49 years Risk of 43% at age 50-59 years Risk of greater than 50% in people ages 60 and older Smoking history: A history of smoking increases the chances of the SPN being malignant. Prior history of cancer: People with a history of cancer in other areas of the body have a greater chance that the SPN is malignant. Occupational risk factors for lung cancer: Exposure to asbestos, radon, nickel, chromium, vinyl chloride, and polycyclic hydrocarbons increases the chance that the SPN is malignant. Travel history: People who have traveled to areas with endemic mycosis (such as histoplasmosis, coccidioidomycosis, or blastomycosis) or a high prevalence of tuberculosis have a higher chance of the SPN being benign. People who have a history of tuberculosis or pulmonary mycosis have a greater chance of the SPN being benign. Blood tests cannot lead to a diagnosis. However, the following tests may indicate whether the SPN is benign or malignant: Anemia (low levels of hemoglobin) or an elevated erythrocyte sedimentation rate (speed at which red blood cells settle in anticoagulated blood) may indicate an underlying cancer or an infectious disease. Elevated levels of liver enzymes, alkaline phosphatase, or serum calcium may indicate that the SPN is cancerous and spreading or that cancer is spreading from other parts of the body to the lung. Persons who have histoplasmosis or coccidioidomycosis may have high levels of immunoglobulin G and immunoglobulin M antibodies specific to these fungi. A tuberculin skin test is used to help determine whether the SPN has been caused by the bacteria Mycobacterium tuberculosis. The test involves injecting the tuberculin antigen (a substance that triggers the immune system to produce cells that attack and try to destroy the antigen) into the skin and observing the body's response. If the injection site swells and reddens, there is a chance that the SPN has been caused by tuberculosis. Chest X-rays Because SPNs are often first detected on chest X-rays, ascertaining whether the nodule is in the lung or outside it is important. A chest X-ray taken from a side position, fluoroscopy, or a CT scan may help confirm the location of the nodule. Although nodules of 5 mm diameter are occasionally found on chest X-rays, SPNs are often 8-10 mm in diameter. Patients who have an older chest X-ray should show it to their health care provider for comparison. This is important, because the growth rate of a nodule can be determined. The doubling time of most malignant SPNs is one to six months, and any nodule that grows more slowly or more rapidly is likely to be benign. Chest X-rays can provide information regarding size, shape, cavitation, growth rate, and calcification pattern. All of these features can help determine whether the lesion is benign or malignant. However, none of these features is entirely specific for lung cancer. Characteristics that may help establish the diagnosis with reasonable certainty include (1) a benign pattern of calcification, (2) a growth rate that is either too slow or too fast to be lung cancer, (3) a specific shape or appearance of the nodule consistent with that of a benign lesion, and (4) unequivocal evidence of another benign disease process. CT scan The CT scan is an invaluable aid in identifying features of the nodule and determining the likelihood of cancer. In addition to the features seen on a chest X-ray, a CT scan of the chest allows better assessment of the nodule. The advantages of a CT scan over chest X-ray include the following: Better resolution: Nodules as small as 3-4 mm can be detected. Features of the SPN are better visualized on CT scan, thereby aiding the diagnosis. Better localization: A nodule's location can be more accurately determined. Areas that are difficult to assess on X-rays are visualized better on a CT scan. CT scanning provides more details of the internal structures and more readily shows calcifications. If the CT scan demonstrates fat within the nodule, the lesion is benign. This is specific for a benign lesion. CT scanning helps distinguish between a neoplastic abnormality and an infective abnormality. Positron emission tomography ( PET) Malignant cells need more energy than normal cells and benign abnormalities; therefore, they consume more sugar. PET involves a radiolabeled substance to measure this activity. Malignant nodules absorb more of the substance than benign nodules and normal tissue and can be readily identified on the 3-dimensional, colored image. PET scan is an accurate, noninvasive exam, but the procedure is expensive. Single-photon emission computed tomography Single-photon emission computed tomography ( SPECT) imaging is performed using a radiolabeled substance, technetium Tc P829. SPECT scans are less expensive than PET scans but have comparable sensitivity and specificity. However, the test has not been evaluated in a large number of people and it is not widely available. In addition, the SPECT scans are less sensitive for nodules smaller than 20 mm in diameter. Biopsy (a sample of cells is removed for examination under a microscope): Different ways are used to collect biopsy samples from the airway or lung tissue where the SPN is located. Bronchoscopy: This procedure is used for SPNs that are situated closer to the walls of the airways. A bronchoscope (a thin, flexible, lighted tube with a tiny camera at the end) is inserted through the mouth or nose and down the windpipe. From there, it can be inserted into the airways (bronchi) of the lungs. During bronchoscopy, the health care professional takes a biopsy sample from the SPN. If the lesion is not easily accessible on the airway wall or is smaller than 2 cm in diameter, a needle biopsy may be performed. This procedure is called a transbronchial needle aspiration ( TBNA) biopsy. Transthoracic needle aspiration ( TTNA) biopsy: This type of biopsy is used if the lesion is not easily accessible on the airway wall or is smaller than 2 cm in diameter. If the SPN is on the periphery of the lung, a biopsy sample has to be taken with the help of a needle inserted through the chest wall and into the SPN. It is usually performed with CT guidance. With SPNs larger than 2 cm in diameter, the diagnostic accuracy is higher (90%-95%). However, the accuracy decreases (60%-80%) in nodules that are smaller than 2 cm in diameter. Video-assisted thoracoscopy ( VATS) is performed with the help of a thoracoscope (a flexible, lighted tube with a tiny camera at the end) inserted into the chest through a small cut on the chest wall. The camera displays the image on a TV screen, and the surgeon uses the display to guide the operation. This is an option that may be used to remove the nodule for both treatment and for confirming diagnosis. Based on the results of exams and tests, a person with SPN can be divided into one of the following three groups: Persons with probable benign SPN: Persons who have been diagnosed with probable benign SPN may need to undergo further serial testing such as chest X-ray or CT scans every three to four months in the first year, every six months in the second year, and once every year for up to five years. Determining that the SPN is benign is typically based on factors that include: Persons younger than age 35 without other risk factors Benign appearance on chest X-ray Stability of the SPN over a period of two years on chest X-rays. Other factors include gender, ethnicity, appearance of nodule, location of nodule, smoking history, medical history, and history of exposure to radon, asbestos or uranium. Persons with a malignant SPN: Persons who have been diagnosed with a malignant SPN based on the results of the exams and tests should have the nodule surgically removed. Persons with SPN that cannot be classified as either benign or malignant: Most persons fall into this category. However, as many as 75% of these patients have malignant nodules on further evaluation. Therefore, such persons are also advised to have it surgically removed. The SPN may be surgically removed in patients who have (1) a moderate-to-high risk for cancer and clinical signs that indicate that the nodule is malignant or (2) a nodule whose malignancy status cannot be determined even after a biopsy. SPN is removed surgically by either thoracotomy (open lung surgery) or a video-assisted thoracoscopic surgery ( VATS). Thoracotomy involves making a cut in the chest wall and removing small wedges of lung tissue. Patients undergoing this procedure are usually required to stay in the hospital for several days afterward. Video-assisted thoracoscopy is performed with the help of a thoracoscope (a flexible, lighted tube with a tiny camera at the end) inserted into the chest through a small cut on the chest wall. The camera displays the image on a TV screen, and the surgeon uses the display to guide the operation. Its advantages over thoracotomy include a shorter recovery time and a smaller incision. Follow-up Persons who have been diagnosed with a benign appearing SPN should schedule serial follow- up testing as guided by their doctor. Avoiding the possible causes may help prevent SPN from forming. Possible avoidable causes include the following: Smoking Traveling to areas with lots of cases of mycosis (histoplasmosis, coccidioidomycosis, blastomycosis) or to areas with a high prevalence of tuberculosis Occupational exposure to risk factors for lung cancer (such as asbestos, radon, nickel, chromium, vinyl chloride, polycyclic hydrocarbons) Most SPNs are benign, but they may represent an early stage of lung cancer. The 5-year survival rate for diagnosed lung cancer is 55% for localized disease and 4% for advanced disease. The only chance for cure of early lung cancer that presents as a SPN is prompt diagnosis and treatment.