A lung nodule or pulmonary nodule is a relatively small focal density in the
lung
The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
. A solitary pulmonary nodule (SPN) or coin lesion, is a
mass
Mass is an Intrinsic and extrinsic properties, intrinsic property of a physical body, body. It was traditionally believed to be related to the physical quantity, quantity of matter in a body, until the discovery of the atom and particle physi ...
in the
lung
The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
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 found in up to 0.2% of
chest X-ray
A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...
s
and around 1% of
CT scan
A computed tomography scan (CT scan), formerly called computed axial tomography scan (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 or ...
s.
The
nodule
Nodule may refer to:
* Nodule (geology), a small rock or mineral cluster
* Manganese nodule, a metallic concretion found on the seafloor
*Nodule (medicine), a small aggregation of cells
*Root nodule
Root nodules are found on the roots of plants, ...
most commonly represents a
benign
Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer.
A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...
tumor such as a
granuloma
A granuloma is an aggregation of macrophages (along with other cells) that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such sub ...
or
hamartoma
A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...
, but in around 20% of cases it represents a
malignant
Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer.
A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
,
especially in
older adults
Old age is the range of ages for people nearing and surpassing life expectancy. People who are of old age are also referred to as: old people, elderly, elders, senior citizens, seniors or older adults. Old age is not a definite biological sta ...
and
smokers. Conversely, 10 to 20% of patients with
lung cancer
Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
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"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
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
The thoracic wall or chest wall is the boundary of the thoracic cavity.
Structure
The bony skeletal part of the thoracic wall is the rib cage, and the rest is made up of muscle, skin, and fasciae.
The chest wall has 10 layers, namely (from ...
or skin, such as a
nipple
The nipple is a raised region of tissue on the surface of the breast from which, in lactating females, breast milk, milk from the mammary gland leaves the body through the lactiferous ducts to Breastfeeding, nurse an infant. The milk can flow th ...
, a healing
rib fracture
A rib fracture is a break in a rib bone. This typically results in chest pain that is worse with inspiration. Bruising may occur at the site of the break. When several ribs are broken in several places a flail chest results. Potential complicat ...
or
electrocardiographic
Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity through repeated cardiac cycles.
It is an electrogram of the heart which is a graph of voltage versus time of t ...
monitoring.
The most important cause to exclude is any form of
lung cancer
Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
, 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). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
,
carcinoid tumor
A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, whe ...
and a solitary
metastasis
Metastasis is a pathogenic agent's spreading 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, ...
to the lung (common unrecognised primary tumor sites are
melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
s,
sarcoma
A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues.
Sarcom ...
s or
testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility.
Risk factors include an c ...
). Benign tumors in the lung include
hamartoma
A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...
s and
chondromas.
The most common benign coin lesion is a
granuloma
A granuloma is an aggregation of macrophages (along with other cells) that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such sub ...
(inflammatory
nodule
Nodule may refer to:
* Nodule (geology), a small rock or mineral cluster
* Manganese nodule, a metallic concretion found on the seafloor
*Nodule (medicine), a small aggregation of cells
*Root nodule
Root nodules are found on the roots of plants, ...
), for example due to
tuberculosis
Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
or a
fungal infection
Fungal infection, also known as mycosis, is a disease caused by fungi. Different types are traditionally divided according to the part of the body affected: superficial, subcutaneous, and systemic. Superficial fungal infections include common ...
, such as
Coccidioidomycosis
Coccidioidomycosis (, ) is a mammalian mycosis, fungal disease caused by ''Coccidioides immitis'' or ''Coccidioides posadasii''. It is commonly known as cocci, Valley fever, California fever, desert rheumatism, or San Joaquin Valley fever. Cocci ...
.
Other infectious causes include a
lung abscess
Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection.
This pus-filled cavity is often caused by aspiration, which m ...
,
pneumonia
Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
(including
pneumocystis pneumonia
''Pneumocystis'' pneumonia (PCP), also known as ''Pneumocystis jirovecii'' pneumonia (PJP), is a form of pneumonia that is caused by the yeast-like fungus '' Pneumocystis jirovecii''.
''Pneumocystis'' specimens are commonly found in the lungs o ...
) or rarely
nocardia
''Nocardia'' is a genus of weakly staining Gram-positive, catalase, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (appearing similar to fungi, but being truly bacteria). It contains a total of 8 ...
l infection or worm infection (such as
dirofilariasis or
dog heartworm infestation). Lung nodules can also occur in
immune disorder
An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:
* By the component(s) of the immune system affected
* By whether the immune system is overactive or underactive
* By whether ...
s, 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 h ...
or
granulomatosis with polyangiitis
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), after Nazi German physician Friedrich Wegener, is a rare, long-term, systemic disorder that involves the formation of granulomas and vasculitis, inflammatio ...
, or
organizing pneumonia
Cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia (BOOP), is an inflammation of the bronchioles (bronchiolitis) and surrounding tissue in the lungs. It is a form of idiopathic interstitial pne ...
.
A solitary lung nodule can be found to be an
arteriovenous malformation
An arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. Usually congenital, this vascular anomaly is widely known because of its occurrence in the central nervous system (usually ...
, a
hematoma
A hematoma, also spelled haematoma, or blood suffusion is a localized bleeding outside of blood vessels, due to either disease or trauma including injury or surgery and may involve blood continuing to seep from broken capillaries. A hematoma is ...
or an
infarction
Infarction is tissue death (necrosis) due to Ischemia, inadequate blood supply to the affected area. It may be caused by Thrombosis, artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as a ...
zone. It may also be caused by
bronchial atresia,
sequestration, an inhaled
foreign body
A foreign body (FB) is any object originating outside the body of an organism. In machinery, it can mean any unwanted intruding object.
Most references to foreign bodies involve propulsion through natural orifices into hollow organs.
Foreign b ...
or
pleural plaque.
Risk factors
Risk factors for incidentally discovered nodules are mainly:
*
General risk factors of lung cancer such as exposure to
tobacco smoking
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...
or other
carcinogen
A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
s such as
asbestos
Asbestos ( ) is a group of naturally occurring, Toxicity, toxic, carcinogenic and fibrous silicate minerals. There are six types, all of which are composed of long and thin fibrous Crystal habit, crystals, each fibre (particulate with length su ...
and previously diagnosed cancer,
respiratory infection
Respiratory tract infections (RTIs) are infectious diseases involving the lower or upper respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tra ...
s, or
chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...
.
* 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
A fissure is a long, narrow crack opening along the surface of Earth. The term is derived from the Latin word , which means 'cleft' or 'crack'. Fissures emerge in Earth's crust, on ice sheets and glaciers, and on volcanoes.
Ground fissure
A ...
or the
pleura
The pleurae (: pleura) are the two flattened closed sacs filled with pleural fluid, each ensheathing each lung and lining their surrounding tissues, locally appearing as two opposing layers of serous membrane separating the lungs from the med ...
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 subpleural nodule.png, subpleural nodule.][
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 is any air-filled enlargement in the body's tissues. Most commonly emphysema refers to the permanent enlargement of air spaces (alveoli) in the lungs, and is also known as pulmonary emphysema.
Emphysema is a lower respiratory tract di ...
and/or fibrosis
Fibrosis, also known as fibrotic scarring, is the development of fibrous connective tissue in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease.
Repeated injuries, ch ...
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 CT scan, X-ray computed tomography (CT) using radiocontrast. Radiocontrasts for X-ray CT are generally Iodinated contrast, iodine-based types. This is useful to highlight structure ...
, a solitary nodule with an enhancement off less than 15 Hounsfield units (HU), whereas a higher enhancement indicates a malignant tumor (with a sensitivity estimated at 98%).[ Updated: Sep 30, 2018]
* Areas of fatty tissue (−40 to −120 HU) indicates a hamartoma
A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...
. 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
An aspergilloma is a clump of mold which exists in a body cavity such as a paranasal sinus or an organ such as the lung. By definition, it is caused by fungi of the genus ''Aspergillus''.
Signs and symptoms
People with aspergillomata typically re ...
).[
]
* 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
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and ...
.[
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
The Hounsfield scale ( ), named after Sir Godfrey Hounsfield, is a quantitative scale for describing radiodensity. It is frequently used in CT scans, where its value is also termed CT number.
Definition
The Hounsfield unit (HU) scale is a linear t ...
, 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, blood tests, 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 Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
, atelectasis
Atelectasis is the partial collapse or closure of a lung resulting in reduced or absence in gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the Pulmonary alveolus, alveoli are deflated down to l ...
(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
Unnecessary health care (overutilization, overuse, or overtreatment) is health care provided with a higher volume or cost than is appropriate.
In the United States, where health care costs are the highest as a percentage of GDP, overuse was the ...
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, r ...
(PET scan) is appropriate (if available). It can be done simultaneously as a CT scan in the form of PET-CT. 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 ''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 cellular processes; the co ...
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
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...
of pulmonary nodules include magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
(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 is, ...
(SPECT).
Histopathology
For cases suspicious enough to proceed to biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...
, small biopsies can be obtained by fine needle aspiration
Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, ...
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
Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, a ...
(which can be done under CT guidance). Needle aspiration can only retrieve groups of cells for cytology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...
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
A pneumothorax is collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and dyspnea, shortness of breath. In a minority of cases, a one-way valve is ...
). However, not all these cases of pneumothorax need treatment with a chest tube
A chest tube (also chest drain, thoracic catheter, tube thoracostomy or intercostal drain) is a drain (surgery), surgical drain that is inserted through the chest wall and into the pleural space or the Mediastinum. The insertion of the tube is som ...
.
Management
Excision
Where workup indicates a high risk of cancer, excision can be performed by thoracotomy
A thoracotomy is a surgical procedure that involves cutting open the chest wall to gain access into the pleural cavity, It is mostly performed by specialist cardiothoracic surgeons, although emergency physicians or paramedics occasionally also ...
or video-assisted thoracoscopic surgery, which can also confirm the diagnosis by microscopical examination.
See also
* Minimally invasive adenocarcinoma of the lung
Footnotes
External links
{{Respiratory tract neoplasia
Lung cancer