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A lung nodule or pulmonary nodule is a relatively small focal density in the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
. 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 elementar ...
in the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
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, 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 med ...
s and around 1% of CT scans. The nodule most commonly represents a
benign 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 ...
tumor such as a granuloma 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. 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 b ...
, especially in
older adults Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms for people at this age include old people, the elderly (worldwide usage), OAPs (British usage ...
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 tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
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 Segmental resection (or segmentectomy) is a surgical procedure to remove part of an organ or gland, as a sub-type of a resection, which might involve removing the whole body part. It may also be used to remove a tumor and normal tissue around i ...
. 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 The nipple is a raised region of tissue on the surface of the breast from which, in females, milk leaves the breast through the lactiferous ducts to feed an infant. The milk can flow through the nipple passively or it can be ejected by smooth mu ...
, 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 complicatio ...
or
electrocardiographic Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...
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 tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
, 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 enlar ...
,
carcinoid tumor A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) a ...
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
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
s,
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 sar ...
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 ...
). 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
chondroma A chondroma is a benign cartilaginous tumor, which is encapsulated with a lobular growing pattern. Tumor cells (chondrocytes, cartilaginous cells) resemble normal cells and produce the cartilaginous matrix (amorphous, basophilic material). Prese ...
s. 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 ...
or a fungal infection, such as
Coccidioidomycosis Coccidioidomycosis (, ), commonly known as cocci, Valley fever, as well as California fever, desert rheumatism, or San Joaquin Valley fever, is a mammalian fungal disease caused by '' Coccidioides immitis'' or ''Coccidioides posadasii''. Coccid ...
. 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 may ...
,
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 severity ...
(including pneumocystis pneumonia) or rarely nocardial infection or worm infection (such as
dirofilariasis Dirofilariasis is an infection by parasites of the genus ''Dirofilaria''. It is transmitted through a mosquito bite; its main hosts include dogs and wild canids. These can give rise to granulomas in the pulmonary artery. Some common symptoms incl ...
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 t ...
s, such as
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
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 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 pn ...
. A solitary lung nodule can be found to be an arteriovenous malformation, a hematoma or an
infarction Infarction is tissue death (necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from the ...
zone. It may also be caused by bronchial atresia, sequestration, an inhaled foreign body 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 simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
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 subs ...
s such as
asbestos Asbestos () is a naturally occurring fibrous silicate mineral. There are six types, all of which are composed of long and thin fibrous crystals, each fibre being composed of many microscopic "fibrils" that can be released into the atmosphere b ...
and previously diagnosed cancer,
respiratory infection Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI ...
s, or
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
. * 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 ...
or the
pleura The pulmonary pleurae (''sing.'' pleura) are the two opposing layers of serous membrane overlying the lungs and the inside of the surrounding chest walls. The inner pleura, called the visceral pleura, covers the surface of each lung and dips b ...
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 alve ...
and/or
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
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 that ...
, a solitary nodule with an enhancement off less than 15
Hounsfield unit 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 tr ...
s (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 rem ...
).
* 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 Ground-glass opacity (GGO) is a finding seen on chest x-ray (radiograph) or computed tomography (CT) imaging of the lungs. It is typically defined as an area of hazy opacification (x-ray) or increased attenuation (CT) due to air displacement by ...
. File:CT of part solid lung nodule.png, Part solid nodule. File:CT of ground glass lung nodule.png,
Ground glass opacity Ground-glass opacity (GGO) is a finding seen on chest x-ray (radiograph) or computed tomography (CT) imaging of the lungs. It is typically defined as an area of hazy opacification (x-ray) or increased attenuation (CT) due to air displacement by ...
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 by processes of sprouting and splitting ...
.
Air bronchogram An air bronchogram is defined as a pattern of air-filled bronchi on a background of airless lung. Material was copied from this source, which is available under Creative Commons Attribution 4.0 International License __TOC__ Consolidations In pulm ...
s 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 tr ...
, 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 Medical diagnosis (abbreviated Dx, Dx, or Ds) is the process of determining which disease or condition explains a person's symptoms and signs. It is most often referred to as diagnosis with the medical context being implicit. The information re ...
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 severity ...
,
atelectasis Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct ...
(lung collapse) or lymphadenopathies (swollen lymph nodes).


CT scan

For incidentally detected nodules on CT scan,
Fleischner Society The Fleischner Society is an international, multidisciplinary medical society for thoracic radiology, dedicated to the diagnosis and treatment of diseases of the chest. Founded in 1969 by eight radiologists whose predominant professional interests ...
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 Metabolism, metabolic processes, and in other physiological activities including bl ...
(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) scan ...
. 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 ''Sensitivity'' and ''specificity'' mathematically describe the accuracy of a test which reports the presence or absence of a condition. Individuals for which the condition is satisfied are considered "positive" and those for which it is not are ...
). 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 cell ...
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 A tuberculoma is a clinical manifestation of tuberculosis which conglomerates tubercles into a firm lump, and so can mimic cancer tumors of many types in medical imaging studies. They often arise within individuals in whom a primary tuberculosis ...
.


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 rev ...
of pulmonary nodules include
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(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, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
, 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, aft ...
or
bronchoscopy Bronchoscopy is an endoscopic technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument (bronchoscope) is inserted into the airways, usually through the nose or mouth, or occasionally through a trac ...
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 Bronchoscopy is an endoscopic technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument (bronchoscope) is inserted into the airways, usually through the nose or mouth, or occasionally through a trac ...
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, aft ...
(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 an abnormal 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 shortness of breath. In a minority of cases, a one-way valve i ...
). 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 surgical drain that is inserted through the chest wall and into the pleural space or the mediastinum in order to remove clinically undesired substance ...
.


Management


Excision

Where workup indicates a high risk of cancer, excision can be performed by
thoracotomy A thoracotomy is a surgical procedure to gain access into the pleural space of the chest. It is performed by surgeons (emergency physicians or paramedics under certain circumstances) to gain access to the thoracic organs, most commonly the hea ...
or
video-assisted thoracoscopic surgery Video-assisted thoracoscopic surgery (VATS) is a type of minimally invasive thoracic surgery performed using a small video camera mounted to a fiberoptic thoracoscope (either 5 mm or 10 mm caliber), with or without angulated visuali ...
, 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