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A lung nodule or pulmonary nodule is a relatively small focal density in the lung. A solitary pulmonary nodule (SPN) or coin lesion, is a
mass Mass is an intrinsic property of a body. It was traditionally believed to be related to the quantity of matter in a physical body, until the discovery of the atom and particle physics. It was found that different atoms and different element ...
in the lung smaller than three centimeters in diameter. A pulmonary micronodule has a diameter of less than three millimetres. There may also be multiple nodules. One or more lung nodules can be an
incidental finding Incidental medical findings are previously undiagnosed medical or psychiatric conditions that are discovered unintentionally and during evaluation for a medical or psychiatric condition. Such findings may occur in a variety of settings, including ro ...
found in up to 0.2% of
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in me ...
s and around 1% of
CT scan A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
s. The nodule most commonly represents a benign tumor such as a granuloma or hamartoma, but in around 20% of cases it represents a
malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, especially in older adults and smokers. Conversely, 10 to 20% of patients with
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
are diagnosed in this way. If the patient has a history of smoking or the nodule is growing, the possibility of cancer may need to be excluded through further radiological studies and interventions, possibly including surgical resection. The
prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
depends on the underlying condition.


Causes

Not every round spot on a radiological image is a solitary pulmonary nodule: it may be confused with the projection of a structure of the chest wall or skin, such as a nipple, a healing rib fracture or electrocardiographic monitoring. The most important cause to exclude is any form of
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
, including rare forms such as primary pulmonary
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enl ...
, carcinoid tumor and a solitary
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
to the lung (common unrecognised primary tumor sites are melanomas,
sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sa ...
s or testicular cancer). Benign tumors in the lung include hamartomas and chondromas. The most common benign coin lesion is a granuloma (inflammatory nodule), for example due to
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in w ...
or a fungal infection, such as Coccidioidomycosis. Other infectious causes include a lung abscess,
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
(including pneumocystis pneumonia) or rarely nocardial infection or worm infection (such as dirofilariasis or
dog heartworm ''Dirofilaria immitis'', also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, that causes dirofilariasis. It is spread from host to host through the bites of mosquitoes. ...
infestation). Lung nodules can also occur in immune disorders, such as
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...
or
granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is a form of vasculitis ...
, or organizing pneumonia. A solitary lung nodule can be found to be an arteriovenous malformation, a hematoma or an infarction zone. It may also be caused by bronchial atresia, sequestration, an inhaled foreign body or
pleural plaque Pleural thickening is an increase in the bulkiness of one or both of the pulmonary pleurae. Causes Pleural plaques Pleural plaques are patchy collections of hyalinized collagen in the parietal pleura. They have a holly leaf appearance on X-ray. ...
.


Risk factors

Risk factors for incidentally discovered nodules are mainly: * General risk factors of lung cancer such as exposure to tobacco smoking or other
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subst ...
s such as asbestos and previously diagnosed cancer, respiratory infections, or chronic obstructive pulmonary disease. * Size: larger size confers a higher risk of cancer * Location: Upper lobe location is a risk factor for cancer, while a location close to a fissure or the pleura indicates a benign lymph node, especially if having a triangular shape. * Margin morphology: a spiculated margin is a risk factor for cancer. Benign causes tend to have a well defined border, whereas lobulated lesions or those with an irregular margin extending into the neighbouring tissue tend to be malignant. In particular, spiculations are highly predictive of malignancy with a positive predictive value up to 90%. Also, a "notch sign", which is an abrupt indentation of the nodule, increases the risk of cancer, but may also be found in granulomatous diseases. File:CT of a round well-delineated solid lung nodule with smooth border.jpg, Round well-delineated solid lung nodule with smooth border. File:CT of a lobulated lung nodule.png, Lobulated nodule. File:CT of a spiculated lung nodule.png, Spiculated lung nodule. File:CT of a lung nodule with a notch sign.png, A "notch sign". File:CT of perifissural nodule.png, A triangular perifissural node can be diagnosed as a benign lymph node. * Multiplicity: Where the presence of up to an additional 3 nodules has been found to increase the risk of cancer, but decrease in case of 4 or more additional ones, likely because it indicates a previous granulomatous infection rather than cancer. * Growth rate: solid cancers generally doubles in volume over between 100 and 400 days, while subsolid cancers (generally representing adenocarcinomas) generally doubles in volume over 3 to 5 years. One volume doubling equals approximately a 26% increase in diameter. * Presence of
emphysema Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces ( pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the a ...
and/or fibrosis is a risk factor for cancer. In comparison, the typical size doubling are less than 20 days for infections, and more than 400 days for benign nodules. * Enhancement: If the exam is done as a combined non-contrast and
contrast CT Contrast CT, or contrast enhanced computed tomography (CECT), is X-ray computed tomography (CT) using radiocontrast. Radiocontrasts for X-ray CT are generally iodine-based types. This is useful to highlight structures such as blood vessels tha ...
, a solitary nodule with an enhancement off less than 15 Hounsfield units (HU), whereas a higher enhancement indicates a malignant tumor (with a
sensitivity Sensitivity may refer to: Science and technology Natural sciences * Sensitivity (physiology), the ability of an organism or organ to respond to external stimuli ** Sensory processing sensitivity in humans * Sensitivity and specificity, statisti ...
estimated at 98%). Updated: Sep 30, 2018 * Areas of fatty tissue (−40 to −120 HU) indicates a hamartoma. However, only about 50% of hamartomas are fat containing. * If there is a central cavity, then a thin wall points to a benign cause whereas a thick wall is associated with malignancy (especially 4 mm or less versus 16 mm or more). File:CT of a fat containing hamartoma.png, Low attenuating nodule (in this case a fat containing hamartoma). File:CT of an aspergilloma.png, Cavitation with relatively thick wall, in this case aspergilloma). * In case of calcifications, a popcorn-like appearance indicates a hamartoma, which is benign. * In case of subsolid nodules, being part solid has a higher risk of cancer than being purely ground glass opacity. File:CT of part solid lung nodule.png, Part solid nodule. File:CT of ground glass lung nodule.png, Ground glass opacity nodule. * Pleural retraction is far more common in cancers. It is the pulling of visceral pleura towards the nodule. File:CT of a lung nodule with pleural retraction.png, Nodule with pleural retraction. File:CT of a subpleural nodule with pleural retraction.png, In this case, pleural retraction is seen as a triangular fat component. * A lung nodule abutting a pulmonary cyst is a rare finding, yet indicating cancer. * Bubble-like lucencies in the nodule indicate cancer: File:CT of spiculated lung nodule with bubble-like lucencies.png File:CT of lung nodule with bubble-like lucencies.png * Vascular convergence is where vessels converge to a nodule without adjoining or contacting the edge of the nodule, and is mainly seen in peripheral subsolid lung cancers. It reflects angiogenesis. Air bronchograms is defined as a pattern of air-filled bronchi on a background of airless lung, and may be seen in both benign and malignant nodules, but certain patterns thereof may help in risk stratification. CT densitometry, measuring absolute attenuation on the Hounsfield scale, has low sensitivity and specificity and is not routinely employed, apart from helping to distinguish solid from ground glass lesions, and to confirm visible fatty areas or calcifications.


Diagnosis

A diagnostic workup can include a variety of scans and biopsies.


Definition

Nodular density is used to distinguish larger lung tumors, smaller infiltrates or masses with other accompanying characteristics. An often used formal radiological definition is the following: a single lesion in the lung completely surrounded by functional lung tissue with a diameter less than 3 cm and without associated
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
, atelectasis (lung collapse) or lymphadenopathies (swollen lymph nodes).


CT scan

For incidentally detected nodules on CT scan, Fleischner Society guidelines are given in table below. For multiple nodes, management is based on the most suspicious node. These guidelines do not apply in lung cancer screening, in patients with immunosuppression, or in patients with known primary cancer. More frequent CT scans than what is recommended has not been shown to improve outcomes but will increase radiation exposure and the unnecessary health care can be expected to make the patient anxious and uncertain., which cites * *


PET scan

If there is an intermediate risk of malignancy, further imaging with
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
(PET scan) is appropriate (if available). It can be done simultaneously as a CT scan in the form of
PET-CT Positron emission tomography–computed tomography (better known as PET-CT or PET/CT) is a nuclear medicine technique which combines, in a single gantry, a positron emission tomography (PET) scanner and an x-ray computed tomography (CT) scann ...
. Around 95% of patients with a malignant nodule will have an abnormal PET scan, while around 78% of patients with a benign nodule will look normal on PET (this is the test
sensitivity and specificity In medicine and statistics, sensitivity and specificity mathematically describe the accuracy of a test that reports the presence or absence of a medical condition. If individuals who have the condition are considered "positive" and those who do ...
). Thus, an abnormal PET scan will reliably pick up cancer, but several other types of nodules (inflammatory or infectious, for example) will also show up on a PET scan. If the nodule has a diameter of less than one centimeter, PET scans are often avoided because of an increased risk of falsely normal results. Cancerous lesions usually have a high
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...
on PET, as demonstrated by their high uptake of FDG (a radioactive sugar). File:PET-CT of a tuberculoma.png, PET-CT of a tuberculoma.


Other imaging

Other potential forms of medical imaging of pulmonary nodules include magnetic resonance imaging (MRI) or
single photon emission computed tomography Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that i ...
(SPECT).


Histopathology

For cases suspicious enough to proceed to
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a d ...
, small biopsies can be obtained by fine needle aspiration or bronchoscopy are commonly used for diagnosis of lung nodules. CT guided percutaneous transthoracic needle biopsies have also proven to be very helpful in the diagnosis of SPN. In selected cases, nodules can also be sampled through the airways using bronchoscopy or through the chest wall using fine-needle aspiration (which can be done under CT guidance). Needle aspiration can only retrieve groups of cells for cytology and not a tissue cylinder or biopsy, precluding evaluation of the tissue architecture. Theoretically, this makes the diagnosis of benign conditions more difficult, although rates higher than 90% have been reported. Complications of the latter technique include hemorrhage into the lung and air leak in the pleural space between the lung and the chest wall ( pneumothorax). However, not all these cases of pneumothorax need treatment with a chest tube.


Management


Excision

Where workup indicates a high risk of cancer, excision can be performed by thoracotomy or video-assisted thoracoscopic surgery, which can also confirm the diagnosis by microscopical examination.


See also

*
Minimally invasive adenocarcinoma of the lung Minimally invasive adenocarcinoma of the lung (MIA) is defined as a small (≤3 cm), solitary tumour with predominant alveolar epithelial appearance ( lepidic growth), as ''in situ'' adenocarcinoma of the lung, with a zone of focal invasion of ...


Footnotes


External links

{{Respiratory tract neoplasia Lung cancer