How is non-small cell lung cancer diagnosed?
Most lung cancers are not found until they start to cause symptoms. Symptoms can suggest that a person might have lung cancer, but the actual diagnosis is made by looking at lung cells under a microscope.
Common signs and symptoms of lung cancer
Most lung cancers do not cause any symptoms until they have spread too far to be cured, but symptoms do occur in some people with early lung cancer. If you go to your doctor when you first notice symptoms, your cancer might be diagnosed at an earlier stage, when treatment is more likely to be effective. The most common symptoms of lung cancer are:
- A cough that does not go away or gets worse
- Chest pain that is often worse with deep breathing, coughing, or laughing
- Weight loss and loss of appetite
- Coughing up blood or rust-colored sputum (spit or phlegm)
- Shortness of breath
- Feeling tired or weak
- Infections such as bronchitis and pneumonia that don’t go away or keep coming back
- New onset of wheezing
When lung cancer spreads to distant organs, it may cause:
- Bone pain (like pain in the back or hips)
- Neurologic changes (such as headache, weakness or numbness of an arm or leg, dizziness, balance problems, or seizures)
- Jaundice (yellowing of the skin and eyes)
- Lumps near the surface of the body, due to cancer spreading to the skin or to lymph nodes (collections of immune system cells) in the neck or above the collarbone
Most of the symptoms listed above are more likely to be caused by conditions other than lung cancer. Still, if you have any of these problems, it’s important to see your doctor right away so the cause can be found and treated, if needed.
Some lung cancers can cause a group of very specific symptoms. These are often described as syndromes.
Cancers of the top part of the lungs (sometimes called Pancoast tumors) may damage a nerve that passes from the upper chest into your neck. This can cause severe shoulder pain. Sometimes these tumors also cause a group of symptoms called Horner syndrome:
- Drooping or weakness of one eyelid
- Having a smaller pupil (dark part in the center of the eye) in the same eye
- Reduced or absent sweating on the same side of the face
Conditions other than lung cancer can also cause Horner syndrome.
Superior vena cava syndrome
The superior vena cava (SVC) is a large vein that carries blood from the head and arms back to the heart. It passes next to the upper part of the right lung and the lymph nodes inside the chest. Tumors in this area may push on the SVC, which can cause the blood to back up in the veins. This can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. While SVC syndrome can develop gradually over time, in some cases it can become life-threatening, and needs to be treated right away.
Some lung cancers can make hormone-like substances that enter the bloodstream and cause problems with distant tissues and organs, even though the cancer has not spread to those tissues or organs. These problems are called paraneoplastic syndromes. Sometimes these syndromes may be the first symptoms of lung cancer. Because the symptoms affect other organs, patients and their doctors may suspect at first that a disease other than lung cancer is causing them.
Some of the more common paraneoplastic syndromes that can be caused by non-small cell lung cancer include:
- High blood calcium levels (hypercalcemia), which can cause frequent urination, thirst, constipation, nausea, vomiting, belly pain, weakness, fatigue, dizziness, confusion, and other nervous system problems
- Excess growth of certain bones, especially those in the finger tips, which is often painful
- Blood clots
- Excess breast growth in men (gynecomastia)
Again, many of the symptoms listed above are more likely to be caused by conditions other than lung cancer. Still, if you have any of these problems, it’s important to see your doctor right away so the cause can be found and treated, if needed.
Medical history and physical exam
If you have any signs or symptoms that suggest you might have lung cancer, your doctor will want to take a medical history to check for risk factors and learn more about your symptoms. Your doctor will also examine you to look for signs of lung cancer and other health problems.
If the results of the history and physical exam suggest you might have lung cancer, more involved tests will be done. These could include imaging tests and/or getting biopsies of lung tissue.
Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done for a number of reasons both before and after a diagnosis of lung cancer, including:
- To help find a suspicious area that might be cancerous
- To learn how far cancer may have spread
- To help determine if treatment has been effective
- To look for possible signs of cancer coming back after treatment
This is often the first test your doctor will do to look for any masses or spots on the lungs. Plain x-rays of your chest can be done at imaging centers, hospitals, and even in some doctors’ offices. If the x-ray is normal, you probably don’t have lung cancer (although some lung cancers may not show up on an x-ray). If something suspicious is seen, your doctor may order more tests.
Computed tomography (CT) scan
A CT (or CAT) scan is more likely to show lung tumors than routine chest x-rays. A CT scan can also provide precise information about the size, shape, and position of any lung tumors and can help find enlarged lymph nodes that might contain cancer that has spread from the lung. This test can also be used to look for masses in the adrenal glands, liver, brain, and other internal organs that might be due to the spread of lung cancer.
The CT scan is a test that uses x-rays to produce detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. A computer then combines these pictures into images of slices of the part of your body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body.
Before the CT scan, you may be asked to drink a contrast solution or you may get an injection of a contrast solution through an IV (intravenous) line. This helps better outline structures in your body. The contrast may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or low blood pressure can occur. Be sure to tell the doctor if you have any allergies or if you ever had a reaction to any contrast material used for x-rays.
A CT scanner has been described as a large donut, with a narrow table that slides in and out of the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.
CT-guided needle biopsy: If a suspected area of cancer lies deep within the body, a CT scan can be used to guide a biopsy needle precisely into the suspected area. For this procedure, you stay on the CT scanning table, while the doctor advances a biopsy needle through the skin and toward the mass. CT scans are repeated until the doctor can see that the needle is within the mass. A biopsy sample is then removed and looked at under a microscope.
Magnetic resonance imaging (MRI) scan
MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal cord.
Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details.
MRI scans take longer than CT scans (often up to an hour), and are a little more uncomfortable. You have to lie inside a narrow tube, which is confining and can upset people with a fear of enclosed spaces. Special “open” MRI machines can sometimes help with this if needed, but the images may not be as sharp in some cases. MRI machines make buzzing and clicking noises, so some centers provide earplugs to help block this out.
Positron emission tomography (PET) scan
A PET scan can be a very important test if you appear to have early stage lung cancer. Your doctor can use this test to help see if the cancer has spread to nearby lymph nodes or other areas, which can help determine if surgery may be an option for you. This test can also be helpful in getting a better idea whether an abnormal area on a chest x-ray or CT scan might be cancer.
PET scans are also useful if your doctor thinks the cancer may have spread but doesn’t know where. PET can reveal spread of cancer to the liver, bones, adrenal glands, or some other organs. It is not as useful for looking at the brain, since all brain cells use a lot of glucose.
For this test, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body over the next day or so.) Because cancer cells in the body are growing rapidly, they absorb more of the radioactive sugar. After about an hour, you will be moved onto a table in the PET scanner. You lie on the table for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it provides helpful information about your whole body.
Many centers have special machines that can do both a PET and CT scan at the same time (PET/CT scan). This lets the doctor compare areas of higher radioactivity on the PET with the more detailed appearance of that area on the CT.
A bone scan can help show if a cancer has spread to the bones.
For this test, a small amount of low-level radioactive material is injected into a vein (intravenously, or IV). The substance settles in areas of bone changes throughout the entire skeleton over the course of a couple of hours. You then lie on a table for about 30 minutes while a special camera detects the radioactivity and creates a picture of your skeleton.
Areas of active bone changes attract the radioactivity and show up as “hot spots.” These areas may suggest metastatic cancer, but arthritis or other bone diseases can also cause the same pattern. To distinguish among these conditions, your cancer care team may use other imaging tests such as plain x-rays or MRI scans to get a better look at the areas that light up, or they may even take biopsy samples of the bone.
PET scans, which are often done in patients with non-small cell lung cancer, can usually show if cancer has spread to the bones, so bone scans aren’t needed very often. Bone scans are done mainly when there is reason to think the cancer may have spread to the bones (because of symptoms such as bone pain) and other test results aren’t clear.
Tests to diagnose lung cancer
Symptoms and the results of certain tests may strongly suggest that a person has lung cancer, but the actual diagnosis of non-small cell lung cancer is made by looking at lung cells under a microscope.
The cells can be taken from lung secretions (sputum or phlegm), removed from a suspicious area (known as a biopsy), or found in fluid removed from the area around the lung (thoracentesis). The choice of which test(s) to use depends on the situation.
A sample of sputum (mucus you cough up from the lungs) is looked at under a microscope to see if it contains cancer cells. The best way to do this is to get early morning samples from you 3 days in a row. This test is more likely to help find cancers that start in the major airways of the lung, such as most squamous cell lung cancers. It may not be as helpful for finding other types of non-small cell lung cancer.
Doctors can often use a hollow needle to get a small sample from a suspicious area (mass). In a fine needle aspiration (FNA) biopsy, the doctor uses a syringe with a very thin, hollow needle (thinner than the ones used for blood tests) to withdraw (aspirate) cells and small fragments of tissue. In a core biopsy, a larger needle is used to remove one ore more small cylinders (cores) of tissue. Core biopsies provide a larger sample than FNA biopsies.
An advantage of needle biopsies is that they don’t require a surgical incision, but in some cases they might not provide enough of a sample to make a diagnosis and to classify DNA changes in the cancer cells that can help doctors choose anticancer drugs.
If the suspected tumor is in the outer portion of the lungs, either kind of biopsy needle can be inserted through the skin on the chest wall. This is called a transthoracic needle biopsy. The area where the needle is to be inserted may be numbed with local anesthesia first. The doctor then guides the needle into the area while looking at the lungs with either fluoroscopy (which is like an x-ray, but the image is shown on a screen rather than on film) or CT scans. Unlike fluoroscopy, CT doesn’t give a constant picture, so the needle is inserted toward the mass, a CT image is taken, and the direction of the needle is guided based on the image. This is repeated a few times until the needle is within the mass.
A possible complication of this procedure is that air may leak out of the lung at the biopsy site and into the space between the lung and the chest wall. This can cause part of the lung to collapse and may cause trouble breathing. This complication, called a pneumothorax, often gets better without any treatment. If not, it is treated by putting a small tube into the chest space and sucking out the air over a day or two, after which it usually heals on its own.
An FNA biopsy may also be done to check for cancer in the lymph nodes between the lungs:
- Transtracheal FNA or transbronchial FNA is done by passing the needle through the wall of the trachea (windpipe) or bronchi (the large airways leading into the lungs) during bronchoscopy or endobronchial ultrasound (described below).
- In some cases an FNA biopsy is done during endoscopic esophageal ultrasound (described below) by passing the needle through the wall of the esophagus.
Bronchoscopy can help the doctor find some tumors or blockages in the larger airways of the lungs.
For this exam, a lighted, flexible fiber-optic tube (called a bronchoscope) is passed through the mouth or nose and down into the windpipe and bronchi. The mouth and throat are sprayed first with a numbing medicine. You may also be given medicine through an intravenous (IV) line to make you feel relaxed.
Small instruments can be passed down the bronchoscope to take biopsies (samples of tissue). The doctor can also sample cells from the lining of the airways with a small brush (bronchial brushing) or by rinsing the airways with sterile saltwater (bronchial washing). These tissue and cell samples are then looked at under a microscope.
Ultrasound is a type of imaging test that uses sound waves to create pictures of the inside of your body. For this test, a small, microphone-like instrument called a transducer gives off sound waves and picks up the echoes as they bounce off body tissues. The echoes are converted by a computer into a black and white image on a computer screen.
For endobronchial ultrasound, a bronchoscope is fitted with an ultrasound transducer at its tip and is passed down into the windpipe. This is done with numbing medicine (local anesthesia) and light sedation.
The transducer can be pointed in different directions to look at lymph nodes and other structures in the mediastinum (the area between the lungs). If suspicious areas such as enlarged lymph nodes are seen on the ultrasound, a hollow needle can be passed through the bronchoscope and guided into these areas to obtain a biopsy. The samples are then sent to a lab to be looked at under a microscope.
Endoscopic esophageal ultrasound
This test is like endobronchial ultrasound, except the doctor passes an endoscope (a lighted, flexible scope) down the throat and into the esophagus (the tube connecting the throat to the stomach). This is done with numbing medicine (local anesthesia) and light sedation.
The esophagus lies just behind the windpipe and is close to some lymph nodes inside the chest to which lung cancer may spread. As with endobronchial ultrasound, the transducer can be pointed in different directions to look at lymph nodes and other structures inside the chest that might contain lung cancer. If enlarged lymph nodes are seen on the ultrasound, a hollow needle can be passed through the endoscope to get biopsy samples of them. The samples are then sent to a lab to be looked at under a microscope.
Mediastinoscopy and mediastinotomy
These procedures may be done to look more directly at and get samples from the structures in the mediastinum (the area between the lungs). They are done in an operating room while you are under general anesthesia (in a deep sleep). The main difference between the two is in the location and size of the incision.
Mediastinoscopy: A small cut is made in the front of the neck and a thin, hollow, lighted tube is inserted behind the sternum (breast bone) and in front of the windpipe to look at the area. Instruments can be passed through this tube to take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas. Looking at the samples under a microscope can show whether cancer cells are present.
Mediastinotomy: The surgeon makes a slightly larger incision (usually about 2 inches long) between the left second and third ribs next to the breast bone. This lets the surgeon reach some lymph nodes that cannot be reached by mediastinoscopy.
If there is a buildup of fluid around the lungs (pleural effusion), doctors can use thoracentesis to find out if it was caused by cancer spreading to the lining of the lungs (pleura). The buildup might also be caused by other conditions, such as heart failure or an infection.
For this procedure, the skin is numbed and a hollow needle is inserted between the ribs to drain the fluid. (In a similar test called pericardiocentesis, fluid is removed from within the sac around the heart.) The fluid is checked under a microscope for cancer cells. Chemical tests of the fluid are also sometimes useful in telling a malignant (cancerous) pleural effusion from a benign (non-cancerous) one.
If a malignant pleural effusion has been diagnosed, thoracentesis may be repeated to remove more fluid. Fluid buildup can keep the lungs from filling with air, so thoracentesis can help the patient breathe better.
Thoracoscopy can be done to find out if cancer has spread to the spaces between the lungs and the chest wall, or to the linings of these spaces. It can also be used to sample tumors on the outer parts of the lungs as well as nearby lymph nodes and fluid, and to assess whether a tumor is growing into nearby tissues or organs. This procedure is not often done just to diagnose lung cancer, unless other tests such as needle biopsies are unable to get enough samples for the diagnosis.
Thoracoscopy is done in the operating room while you are under general anesthesia (in a deep sleep). A small cut (incision) is made in the side of the chest wall. (Sometimes more than one cut is made.) The doctor then inserts a thin, lighted tube with a small video camera on the end through the incision to view the space between the lungs and the chest wall. Using this, the doctor can see potential cancer deposits on the lining of the lung or chest wall and remove small pieces of tissue to be looked at under the microscope. (When certain areas can’t be reached with thoracoscopy, the surgeon may need to make a larger incision in the chest wall, known as a thoracotomy.)
Thoracoscopy can also be used as part of the treatment to remove part of a lung in some early-stage lung cancers. This type of operation, known as video-assisted thoracic surgery (VATS), is described in more detail in the “Surgery for non-small cell lung cancer” section.
Lab tests of biopsy and other samples
Samples that have been collected during biopsies or other tests are sent to a pathology lab. A pathologist, a doctor who uses lab tests to diagnose diseases such as cancer, will look at the samples under a microscope and may do other special tests to help better classify the cancer. (Cancers from other organs can spread to the lungs. It’s very important to find out where the cancer started, because treatment is different depending on the type of cancer.)
The results of these tests are described in a pathology report, which is usually available within about a week. If you have any questions about your pathology results or any diagnostic tests, talk to your doctor. If needed, you can get a second opinion of your pathology report by having your tissue samples sent to a pathologist at another lab recommended by your doctor.
For more information on understanding your pathology report, see the “Lung Pathology” section of our website.
For this test, very thin slices of the sample are attached to glass microscope slides. The samples are then treated with special proteins (antibodies) designed to attach only to a specific substance found in certain cancer cells. If the patient’s cancer cells contain that substance, the antibody will attach to the cells. Chemicals are then added so that antibodies attached to the cells change color. The doctor who looks at the sample under a microscope can see this color change.
In some cases, doctors may look for specific gene changes in the cancer cells that could mean certain targeted drugs might help treat the cancer.
For example, the epidermal growth factor receptor (EGFR) is a protein that sometimes appears in high amounts on the surface of cancer cells and helps them grow. Some newer anti-cancer drugs that target EGFR seem to work best against lung cancers with certain changes in the EGFR gene, which are more common in certain groups, such as non-smokers, women, and Asians. But these drugs don’t seem to be as helpful in patients whose cancer cells have changes in the KRAS gene. Many doctors now test for changes in genes such as EGFR and KRAS to determine if these newer treatments are likely to be helpful.
About 5% of NSCLCs have been found to have a rearrangement in a gene called ALK. This change is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC. Doctors may test cancers for changes in the ALK gene to see if a drug (such as crizotinib) that targets this change may help them.
About 1% to 2% of NSCLCs have a rearrangement in the ROS1 gene, which might make the tumor respond to the targeted drug crizotinib. A similar percentage have a rearrangement in the RET gene. Certain drugs that target cells with RET gene changes might be options for treating these tumors.
Newer lab tests for certain other genes or proteins may also help guide the choice of treatment. Some of these are described in the section “What’s new in non-small cell lung cancer research and treatment?”
Blood tests are not used to diagnose lung cancer. But they can help to get a sense of a person’s overall health; for example, to see if a person is healthy enough to have surgery.
A complete blood count (CBC) determines whether your blood has normal numbers of various cell types. For example, it can show if you are anemic (have a low number of red blood cells), if you could have trouble with bleeding (due to a low number of blood platelets), or if you are at increased risk for infections (because of a low number of white blood cells). This test will be repeated regularly if you are treated with chemotherapy, because these drugs can affect blood-forming cells of the bone marrow.
Blood chemistry tests can help spot abnormalities in some of your organs, such as the liver or kidneys. For example, if cancer has spread to the liver and bones, it may cause abnormal levels of certain chemicals in the blood, such as a higher than normal level of lactate dehydrogenase (LDH).
Pulmonary function tests
Pulmonary function tests (PFTs) are often done after lung cancer is diagnosed to see how well your lungs are working (for example, how much emphysema or chronic bronchitis is present). This is especially important if surgery might be an option in treating the cancer. Surgery to remove lung cancer may mean removing part or all of a lung, so it’s important to know how well the lungs are working beforehand. Some people with poor lung function (like those with lung damage from smoking) don’t have enough lung reserve to withstand removing even part of a lung. These tests can give the surgeon an idea of whether surgery is a good option, and if so, how much lung can safely be removed.
There are different types of PFTs, but they all basically have you breathe in and out through a tube that is connected to a machine that measures airflow.
Sometimes PFTs are coupled with a test called an arterial blood gas. In this test, blood is removed from an artery (most blood tests use blood removed from a vein) to measure the amount of oxygen and carbon dioxide that it contains.
Last Medical Review: 05/22/2013
Last Revised: 05/22/2013