How is small cell lung cancer diagnosed?

Most lung cancers are not found until they start to cause symptoms. Symptoms can suggest that a person may 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 some people with early lung cancer do have symptoms. 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
• Hoarseness
• 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 (collection 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 specific symptoms. These are often described as syndromes.

Horner syndrome

Cancers of the upper 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.

Paraneoplastic syndromes

Some lung cancers may make hormone-like or other 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 first suspect that a disease other than lung cancer is causing them.

Some of the more common paraneoplastic syndromes associated with small cell lung cancer (SCLC) are:

SIADH (syndrome of inappropriate anti-diuretic hormone): In this condition, the cancer makes a hormone (ADH) that causes the kidneys to retain water. This causes salt levels in the blood to become very low. Symptoms of SIADH can include fatigue, loss of appetite, muscle weakness or cramps, nausea, vomiting, restlessness, and confusion. Without treatment, severe cases may lead to seizures and coma.

Cushing syndrome: In some cases, lung cancer cells may make ACTH, a hormone that causes the adrenal glands to secrete cortisol. This can lead to symptoms such as weight gain, easy bruising, weakness, drowsiness, and fluid retention. Cushing syndrome can also cause have high blood pressure and high blood sugar levels (or even diabetes).

Neurologic problems: Small cell lung cancer can sometimes cause the body's immune system to attack parts of the nervous system, which can lead to problems. One example is a muscle disorder called the Lambert-Eaton syndrome. In this syndrome, muscles around the hips become weak. One of the first signs may be trouble getting up from a sitting position. Later, muscles around the shoulder may become weak. A rarer problem is paraneoplastic cerebellar degeneration, which can cause loss of balance and unsteadiness in arm and leg movement, as well as trouble speaking or swallowing. Small cell lung cancer can also cause other nervous system problems, such as muscle weakness, sensation changes, vision problems, or even changes in behavior.

Again, many of the symptoms listed above can also 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 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 may have lung cancer, 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 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 recurrence after treatment

Chest x-ray

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 (but 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

The CT or CAT 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 and organs 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). 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.

CT scans take longer than regular x-rays, and they expose you to a small amount of radiation. The test itself is painless, other than, perhaps, the insertion of the IV line. You need to lie still on a table while it is being done. During the test, the table slides 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.

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 (better) than routine chest x-rays in finding early lung cancers.

Most patients with SCLC will have a CT of the chest and abdomen to look at the lungs and lymph nodes, and to look for masses in the adrenal glands, liver, and other internal organs that may be affected by the spread of lung cancer. Some patients will have a CT of the brain to look for cancer spread, but an MRI may be done instead.

CT guided needle biopsy: In cases where 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 remain 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 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). Special, “open” MRI machines can sometimes help with this if needed, although the images may not be as sharp in some cases. MRI machines make buzzing and clicking noises that you may find disturbing. Some centers provide earplugs to help block this noise out.

Most patients with SCLC will have an MRI scan to look for possible cancer spread to the brain, although a CT scan may be used instead. MRI may also be used to look for possible spread to the spinal cord if the patients have certain symptoms.

Positron emission tomography (PET) scan

For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. The amount of radioactivity used is very low. Cancer cells in the body are growing rapidly, so they absorb large amounts 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.

This can be a very important test if you appear to have early stage (or limited) SCLC. Your doctor can use this test to see if the cancer has spread to lymph nodes or other organs, which can help determine your treatment options. A PET scan can also be helpful in getting a better idea whether an abnormal area on your chest x-ray may be cancer.

PET scans are also useful if your doctor thinks the cancer may have spread but doesn't know where. It 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 machines are able to perform 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. This is the type of PET most often used in SCLC patients.

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 among 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.

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. PET scans can usually show the spread of cancer to bones, so bone scans aren't usually needed if a PET scan has already been done.

Other tests to diagnose lung cancer and its spread

Bronchoscopy

This test may be used to find a lung tumor or to take a sample of a tumor to see if it is cancer. 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 larger airways of the lungs. At the same time, 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.

Endobronchial ultrasound

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 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 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 to get biopsy samples of them. The samples are then sent to a lab to be looked at under a microscope.

This test may be used if the doctor is considering surgery as a part of treatment, which is not often the case for small cell lung cancer. It is much more useful in staging non-small cell lung cancer.

Endoscopic esophageal ultrasound

This technique is similar to 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. Ultrasound images taken from inside the esophagus can help find large lymph nodes 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.

This test may be used if the doctor is considering surgery as a part of treatment, which is not often the case for small cell lung cancer. It is much more useful in staging non-small cell lung cancer.

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. These tests are not often used for cases of small cell lung cancer. They are much more useful in staging non-small cell lung cancer.

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. 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: The surgeon makes a slightly larger incision (usually about 2 inches long) between the second and third ribs next to the breast bone. This allows the surgeon to reach lymph nodes that cannot be reached by mediastinoscopy.

Thoracentesis

Thoracentesis is done to relieve symptoms caused by a buildup of fluid around the lungs (pleural effusion) and to see if this fluid buildup is 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 to look 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 build-up can keep the lungs from filling with air, so thoracentesis can help the patient breathe better.

Thoracoscopy

This procedure can be done to find out if cancer has spread to the space 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 sufficient samples for the diagnosis. It may be done to see if the cancer has spread to the pleura (the membrane around the lung).

Thoracoscopy is done in an 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 the 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" section. Because surgery is not often part of the treatment of SCLC, this test isn’t often needed.

Bone marrow aspiration and biopsy

These tests are done to look for spread of the cancer into the bone marrow. Bone marrow is where new blood cells are made and is found inside certain bones. These tests may be done in patients thought to have limited stage small cell lung cancer but who have blood test results suggesting the cancer may have reached the bone marrow.

The two tests are usually done at the same time. The samples are most often taken from the back of the pelvic (hip) bone.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). The skin over the hip is cleaned. Then the skin and the surface of the bone are numbed with local anesthetic, which may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out a small amount of liquid bone marrow (about 1 teaspoon). Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is twisted as it is pushed down into the bone. The biopsy will likely also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding.

Sampling tissues and cells

Symptoms and the results of imaging tests may strongly suggest that lung cancer is present, but the actual diagnosis of lung cancer is made by looking at lung cells under a microscope.

The cells can be obtained from lung secretions (phlegm), or the cells can be removed 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 have and to help determine how far it may have spread.

A pathologist, a doctor who uses lab tests to diagnose diseases such as cancer, will look at the cells under a microscope. The results will be 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.

Sputum cytology

For this test, a sample of sputum (mucus you cough up from the lungs) is looked at 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 on the chest wall where the needle is to be inserted may be numbed with local anesthesia. The doctor then 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 provide a continuous 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 small sample of the mass is then sucked into a syringe and sent to a lab, where it is looked at under the microscope to see if cancer cells are present. (In some cases, if the diagnosis isn't clear based on the FNA biopsy, a larger needle may be used to remove a slightly bigger piece of lung tissue. This is known as a core needle biopsy.)

A needle biopsy may be useful for getting samples from tumors in the outer portions of the lungs, where other tests such as bronchoscopy (described below) may not be as helpful.

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 take samples of lymph nodes around the trachea (windpipe) and bronchi (the larger airways leading into the lungs). This can be done during a bronchoscopy (described in the previous section). A thin, hollow needle is inserted through the end of the bronchoscope and through the wall of the trachea or bronchus to sample the nearby lymph nodes. This procedure is called a transtracheal FNA or transbronchial FNA and is most accurate when guided by endobronchial ultrasound as described in the previous section.

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 depending on the type of cancer.

Immunohistochemistry

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.

Blood tests

Blood tests are not used to diagnose lung cancer, but they are often done to get a sense of a person's overall health and to help tell if cancer may have spread to other areas.

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 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 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, 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) may be done after lung cancer is diagnosed to see how well your lungs are working. They are generally only needed if surgery might be an option in treating the cancer. Since surgery is rarely used to treat small cell lung cancer, these tests are not often done for patients known to have small cell lung cancer..

There are different types of PFTs, but they all basically involve having you breathe in and out through a tube that is connected to different machines.