Lung cancer

How Is Non-Small Cell Lung Cancer Diagnosed?

Most lung cancers are not found until they start to cause symptoms, at which point they are often already at an advanced stage.

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 and treated while it is curable. Or, at the least, you could live longer with a better quality of life. The most common symptoms of lung cancer are:

• a cough that does not go away
• chest pain that is often worse with deep breathing, coughing, or laughing
• hoarseness
• weight loss and loss of appetite
• bloody or rust-colored sputum (spit or phlegm)
• shortness of breath
• recurring infections such as bronchitis and pneumonia
• new onset of wheezing

When lung cancer spreads to distant organs, it may cause:

• bone pain
• neurologic changes (such as headache, weakness or numbness of a limb, dizziness, or recent onset of a seizure)
• 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

Some lung cancers can cause a group of very specific symptoms. These are often described as "syndromes."

Horner syndrome

Cancer of the top part of the lungs (sometimes called Pancoast tumors) may damage a nerve that passes from the upper chest into your neck. Their most common symptom is severe shoulder pain. Sometimes they 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.

Paraneoplastic syndromes

Some lung cancers may 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 early lung cancer. Because the symptoms affect other organs, patients and their doctors may suspect at first that diseases other than lung cancer cause them.

The most common paraneoplastic syndromes caused by non-small cell lung cancer are:

• high blood calcium levels (hypercalcemia), which can cause frequent urination, constipation, weakness, 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)

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.

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 (health-related interview) to check for risk factors and symptoms. Your doctor will also examine you to look for signs of lung cancer and other health problems.

If symptoms and/or the results of the physical exam suggest lung cancer might be present, more involved tests will likely be done. These might include imaging tests and/or getting biopsies of lung tissue.

Imaging tests

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, including to help find out whether a suspicious area might be cancerous, to learn how far cancer may have spread, and to help determine if treatment has been effective.

Chest x-ray

This is often the first test your doctor will do to look for any masses or spots on the lungs. A plain x-ray of your chest can be done in any outpatient setting. If the x-ray is normal, you probably don't have lung cancer. If something suspicious is seen, your doctor may order additional tests.

Computed tomography (CT) scan

The CT or CAT scan is an x-ray test that produces 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 receive an IV (intravenous) line through which a contrast dye is injected. 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 ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.

In recent years, spiral CT (also known as helical CT) has become available in many medical centers. This type of CT scan uses a faster machine. The scanner part of the machine rotates around the body continuously, allowing doctors to collect the images much more quickly than standard CT. As a result, you do not have to hold your breath for as long while the image is taken. This lowers the chance of "blurred" images occurring as a result of breathing motion. It also lowers the dose of radiation received during the test. The "slices" it images are thinner, which yields more detailed pictures.

A CT scan can provide precise information about the size, shape, and position of any tumors and can help find enlarged lymph nodes that might contain cancer that has spread from the lung. CT scans are more sensitive than routine chest x-rays in finding early lung cancers.

This test can also be used to look for masses in the adrenal glands, brain, and other internal organs that may be affected by the spread of lung cancer.

CT guided needle biopsy: In some cases, a CT scan can be used to guide a biopsy needle precisely into a suspected area of cancer spread. For this procedure, you stay on the CT scanning table, while a radiologist advances a biopsy needle through the skin and toward the location of the mass. CT scans are repeated until the doctors 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

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 are a little more uncomfortable than CT scans. First, they take longer -- often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). Newer, "open" MRI machines can sometimes help with this if needed. The machine also makes buzzing and clicking noises that you may find disturbing. Some centers provide headphones with music to block this out.

MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal cord.

Positron emission tomography (PET) scan

PET scans involve injecting glucose (a form of sugar) that contains a radioactive atom into the blood. The amount of radioactivity used is very low. Because cancer cells in the body are growing rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create 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.

This can be a very important test if you have early stage lung cancer. Your doctor can use this test to see if the cancer has spread to lymph nodes. It is also helpful in getting a better idea whether an abnormal area on your chest x-ray may be cancer.

A PET scan is 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.

Some newer machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the doctor to compare areas of higher radioactivity on the PET with the appearance of that area on the CT.

Bone scan

A bone scan can help show if a cancer has metastasized (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 appear as "hot spots" on your skeleton -- that is, they attract the radioactivity. These areas may suggest the presence of metastatic cancer, but arthritis or other bone diseases can also cause the same pattern. To distinguish between these conditions, your cancer care team may use other imaging tests such as simple 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 the spread of cancer to 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, etc.) and other test results aren't clear.

Procedures that sample tissues and cells

Symptoms and the results of imaging tests may strongly suggest that lung cancer is present, 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 (phlegm) or by removing the cells from a suspicious area (known as a biopsy). One or more of the tests below may be used to find out if a lung mass seen on imaging tests is indeed lung cancer. These tests can also be used to tell the exact type of lung cancer you may have and to help determine how far it may have spread.

A pathologist, a doctor who specializes in using lab tests to diagnose diseases such as cancer, will examine the cells using a microscope. If you have any questions about your pathology results or any diagnostic tests, do not hesitate to ask your doctor. If needed, you can get a second opinion of your pathology report by having your tissue specimen sent to a pathologist at another lab recommended by your doctor.

Sputum cytology

A sample of phlegm (mucus you cough up from the lungs) is viewed under a microscope to see if cancer cells are present. The best way to do this is to get early morning samples from you 3 days in a row.

Fine needle aspiration (FNA) biopsy

A needle biopsy can often be used to get a small sample of cells from a suspicious area. For this test, the skin where the needle is to be inserted is first numbed with local anesthesia. The doctor guides a thin, hollow needle into the area while looking at your 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 continuous picture, so the needle is inserted in the direction of 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 tiny sample of the target area is then sucked into a syringe and looked at under the microscope to see if cancer cells are present.

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 can 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.

A thin needle can also be inserted through the wall of the trachea (windpipe) or bronchus (one of the larger tubes that carry air to the lungs) using a bronchoscope (see below) in order to sample nearby lymph nodes. This procedure, called transtracheal or transbronchial fine needle aspiration, is often used to take samples of lymph nodes around the windpipe and bronchi.

Bronchoscopy

For this exam, a lighted, flexible fiber-optic tube (bronchoscope) is passed through your 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.

Bronchoscopy can help the doctor find some tumors or blockages in the lungs. At the same time, small instruments can be passed down the bronchoscope to take biopsies (samples of tissue) or samples of lung secretions to be looked at under a microscope.

Endobronchial ultrasound (EBUS)

Ultrasound is a type of imaging test that uses sound waves to create images of parts of your body. For this test, a small, microphone-like instrument called a transducer emits 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 that is displayed 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. 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 by ultrasound into the abnormal structures to obtain a biopsy. The samples are then looked at under a microscope.

Endoscopic esophageal ultrasound (EUS)

This technique is similar to endobronchial ultrasound, except it involves using an endoscope (a lighted, flexible scope) that is passed down the throat and into the esophagus (the tube connecting the throat to the stomach), which lies just behind the windpipe. This is done with numbing medicine (local anesthesia) and light sedation.

The esophagus is close to some lymph nodes inside the chest to which lung cancer may spread. Ultrasound images taken from inside the esophagus can be helpful in finding large lymph nodes inside the chest that might contain lung cancer. If suspicious areas (such as 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 looked at under a microscope.

Mediastinoscopy and mediastinotomy

Both of these procedures allow the doctor to look more directly at and sample 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 a mediastinoscopy and a mediastinotomy is in the location and size of the incision.

For a mediastinoscopy, a small cut is made in the front of the neck above the breastbone (sternum) and a thin, hollow, lighted tube is inserted behind the sternum. Special 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 also allows the doctor to look at and remove mediastinal lymph nodes while the patient is under general anesthesia. For 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 allows the surgeon to reach lymph nodes that are not reached by mediastinoscopy.

Thoracentesis

Thoracentesis is done to find out whether or not a build-up of fluid around the lungs (pleural effusion) is the result of cancer spreading to the lining of the lungs (pleura). The build-up might also be caused by a condition such as heart failure or an infection.

For this procedure, the skin is numbed and a needle is placed 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 to look for cancer cells. Chemical tests of the fluid are also sometimes useful in telling a malignant (cancerous) pleural effusion from a benign one.

If a malignant pleural effusion has been diagnosed, thoracentesis may be repeated to remove more fluid. Fluid build-up can prevent the lungs from filling with air, so thoracentesis can help the patient breathe better.

Thoracoscopy

Thoracoscopy can be done to find out if cancer has spread to the space between the lungs and the chest wall, as well as to the linings of these spaces. Most often this procedure is done in the operating room while you are under general anesthesia (in a deep sleep). The doctor inserts a lighted tube with a small video camera on the end through a small cut made in the chest wall to view the space between the lungs and the chest wall. (Sometimes more than one cut is made.) Using this, the doctor can see potential cancer deposits on the lung or lining of the chest wall and remove small pieces of tissue to be looked at under the microscope. Thoracoscopy can also be used to sample lymph nodes and fluid and assess whether a tumor is growing into nearby tissues or organs.

Lab tests of biopsy and other samples

Samples that have been collected during biopsies or other tests are sent to a pathology lab. There, a doctor views the samples under a microscope to find out if they contain cancer and if so, what type of cancer it is. Special tests may be needed 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 for different types of cancer.

Immunohistochemistry (IHC): 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 contains 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 views the sample under a microscope can see this color change.

Molecular tests: In some cases, doctors may look for specific gene changes in the cancer cells that might affect how they are best treated. 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 anti-cancer drugs target EGFR, but they only seem to work against certain cancers. Some doctors may test for changes in genes such as EGFR and K-RAS to determine if these treatments are likely to be helpful. While these tests are available in specialized labs, they are not yet widely used.

Other tests

Blood tests

Blood tests are not used to diagnose lung cancer, but they are done to get a sense of a person's overall health. For example, prior to surgery, blood tests can help tell if a person is healthy enough to have an operation.

A complete blood count (CBC) determines whether your blood has the correct number of various cell types. For example, it can show if you are anemic (have a low number of red blood cells), if you may have trouble with bleeding (due to a low number of blood platelets), or if you are at increased risk for infections (due to 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. If cancer has spread to the liver and bones, it may cause abnormal levels of certain chemical in the blood. For example, spread to these areas may result in a higher than normal level of lactate dehydrogenase (LDH) in the blood.

Pulmonary function tests

Pulmonary function tests (PFTs) are often done after a lung cancer diagnosis to see how well your lungs are working (how much emphysema or chronic obstructive lung disease is present). This is especially important if surgery might be an option in treating the cancer. Because surgical removal of part or all of lung results in lower lung capacity, it's important to know how well the lungs are working beforehand. 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 a few different types of PFTs, but they all basically involve having you breathe in and out through a tube that is connected to different machines.