How is acute myeloid leukemia diagnosed?
Certain signs and symptoms might suggest that a person could have acute myeloid leukemia (AML), but tests are needed to confirm the diagnosis.
Medical history and physical exam
If signs or symptoms suggest you might have leukemia, the doctor will want to get a thorough medical history, including how long you have had symptoms and whether or not you have any risk factors.
During the physical exam, the doctor will likely pay close attention to your eyes, mouth, skin, lymph nodes, liver, spleen, and nervous system, and will look for areas of bleeding or bruising, or possible signs of infection.
If there is reason to think there might be problems caused by abnormal blood cells (anemia, infections, bleeding or bruising, etc.), you will get tests to check your blood cell counts. You might also be referred to a hematologist, a doctor who specializes in diseases of the blood (including leukemia).
Types of samples used to test for acute myeloid leukemia
If signs and symptoms and/or the results of the physical exam suggest you might have leukemia, the doctor will need to check samples of cells from your blood and bone marrow to be sure. Other tissue and cell samples may also be taken in order to help guide treatment.
Blood samples for tests for AML are generally taken from a vein in the arm.
Bone marrow samples
Bone marrow samples are obtained from 2 tests that are usually done at the same time:
- Bone marrow aspiration
- Bone marrow biopsy
The samples are usually taken from the back of the pelvic (hip) bone, but sometimes other bones are used instead. If only an aspiration is to be done, it may be taken from the sternum (breast bone).
In bone marrow aspiration, you lie on a table (either on your side or on your belly). The doctor will clean the skin over the hip and then numb the area and the surface of the bone by injecting a local anesthetic. This 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. 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 pushed down into the bone. This causes a feeling of pressure and may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.
These bone marrow tests are used to help diagnose leukemia, but they are also repeated later to tell if the leukemia is responding to treatment.
The cerebrospinal fluid (CSF) is the liquid that surrounds the brain and spinal cord. AML can sometimes spread to the area around the brain and spinal cord. To check for this spread, doctors remove a sample of CSF for testing. The procedure used to remove this fluid is called a lumbar puncture (spinal tap). A lumbar puncture is not often used to test for AML, unless the patient is having symptoms that could be caused by leukemia cells spreading into the brain and spinal cord.
For this test, the patient may lie on his side or sit up. The doctor first numbs an area of skin on the lower part of the back over the spine. A small, hollow needle is then inserted between the bones of the spine into the area around the spinal cord to withdraw some of the fluid. A lumbar puncture is sometimes used to deliver chemotherapy drugs into the CSF to help prevent or treat the spread of leukemia to the spinal cord and brain.
Lab tests used to diagnose and classify acute myeloid leukemia
One or more of the following lab tests may be done on the samples to diagnose AML and/or to determine the specific subtype of AML.
Complete blood count and peripheral blood smear
The complete blood count (CBC) is a test that measures the amounts of different cells in the blood, such as the red blood cells, white blood cells, and platelets. This test is often done along with a differential (or diff), which looks at the numbers of the different types of white blood cells. For the peripheral blood smear, a sample of blood is looked at under the microscope. Changes in the numbers and the appearance of different types of blood cells often help diagnose leukemia.
Most patients with AML have too many immature white cells in their blood, and not enough red blood cells or platelets. Many of the white blood cells may be myeloblasts (often just called blasts), which are immature blood-forming cells that are not normally found in the blood. These immature cells don’t work like normal, mature white blood cells. These findings may suggest leukemia, but the disease usually is not diagnosed without looking at a sample of bone marrow cells.
Blood chemistry and coagulation tests
These tests measure the amounts of certain chemicals in the blood and the ability of the blood to clot. These tests are not used to diagnose leukemia, but they can help detect liver or kidney problems, abnormal levels of certain minerals in the blood, or problems with blood clotting.
Routine microscopic exams
Samples of blood, bone marrow, or CSF are looked at under a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in cancer and blood diseases).
The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types.
A key element is whether the cells look mature (like normal blood cells) or immature (lacking features of normal blood cells). The most immature cells are called myeloblasts (or blasts for short).
The percentage of blasts in the bone marrow or blood is particularly important. Having at least 20% blasts in the marrow or blood is generally required for a diagnosis of AML. It can also be diagnosed if the blasts are found (using another test) to have a chromosome change that occurs only in a specific type of AML, even if the blast percentage doesn’t reach 20%. Sometimes the blasts look like normal immature cells in the bone marrow. But in normal bone marrow, the blast count is 5% or less.
Sometimes just counting and looking at the cells isn’t enough to provide a clear diagnosis. Additional tests may be used to confirm the diagnosis of AML.
For cytochemistry tests, cells are exposed to chemical stains (dyes) that react with only some types of leukemia cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present. For instance, one stain can help distinguish AML cells from acute lymphocytic leukemia (ALL) cells. The stain causes the granules of most AML cells to appear as black spots under the microscope, but it does not cause ALL cells to change colors.
Flow cytometry and immunohistochemistry
Flow cytometry is often used to look at the cells from bone marrow and blood samples. It is very helpful in determining the exact type of leukemia.
The test looks for certain substances on the surface of cells that help identify what types of cells they are. A sample of cells is treated with special antibodies (man-made immune system proteins) that stick to the cells only if they have these substances. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will make them give off light, which can be measured and analyzed by a computer. Groups of cells can be separated and counted by these methods.
In immunohistochemistry tests, cells from the blood or bone marrow samples are also treated with special antibodies. But instead of using a laser and computer, the sample is treated so that certain types of cells change color when seen under a microscope.
These tests are used for immunophenotyping – classifying leukemia cells according to the substances (antigens) on their surfaces. Leukemia cells can have different antigens depending on which type of cells they start in and how mature they are, and this information can be helpful in AML classification.
For this test, a cell’s chromosomes (long strands of DNA) are looked at under a microscope. Normal human cells contain 23 pairs of chromosomes, each of which are a certain size and stain a certain way. In some cases of AML, the cells have chromosome changes that can be seen under a microscope.
For instance, 2 chromosomes may swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. This change, called a translocation, can usually be seen under a microscope. Other types of chromosome changes are also possible (see below). Recognizing these changes can help identify certain types of AML and can be important in determining a patient’s outlook.
It usually takes about 2 to 3 weeks to get results for this test because the leukemia cells must be grown in lab dishes for a couple of weeks before their chromosomes can be looked at under the microscope.
The results of cytogenetic testing are written in a shorthand form that describes the chromosome changes:
- A translocation, written as t(8;21), for example, means a part of chromosome 8 is now located on chromosome 21, and vice versa.
- An inversion, written as inv(16), for example, means that part of the chromosome 16 is now in reverse order but is still attached to the chromosome.
- A deletion, written as del(7) or -7, for example, indicates part of chromosome 7 has been lost.
- An addition or duplication, +8, for example, means that all or part of chromosome 8 has been duplicated, and too many copies of it are found within the cell.
Not all chromosome changes can be seen under a microscope. Other lab tests can often detect these changes.
Fluorescent in situ hybridization (FISH)
This is similar to cytogenetic testing. It uses special fluorescent dyes that only attach to specific genes or parts of particular chromosomes. FISH can find the chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.
FISH can be used to look for changes in specific genes or parts of chromosomes. It can be used on regular blood or bone marrow samples without growing them in a lab first. This means the results are often available more quickly than with regular cytogenetic testing. The drawback is that it only looks for certain gene or chromosome changes, so the doctor has to know what he or she is looking for before the test is run.
Polymerase chain reaction (PCR)
This is a very sensitive test that can also find some gene and chromosome changes too small to be seen under a microscope. It is helpful in finding gene changes that are in only a few cells, making it good for finding small numbers of leukemia cells in a sample (like after treatment). Like FISH, this test only looks for certain gene or chromosome changes, so the doctor has to know what he or she is looking for before the test is run.
Imaging tests for acute myeloid leukemia
Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to create pictures of the inside of the body. Leukemia doesn’t usually form tumors, so imaging tests are not often helpful in making the diagnosis. When imaging tests are done in people with AML, it is most often to look for infections or other problems, rather than to look for the leukemia itself. In a few cases, imaging tests may be done to help determine the extent of the disease, if it is thought it may have spread beyond the bone marrow and blood.
Routine chest x-rays may be done if a lung infection is suspected.
Computed tomography (CT) scan
This test can help show if any lymph nodes or organs in your body are enlarged. It isn’t usually needed to diagnose AML, but it may be done if your doctor suspects the leukemia is growing in an organ, like your spleen.
The CT scan uses x-rays to make detailed, cross-sectional images of your body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs).
Before the test, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV line through which the contrast dye is injected. Injecting contrast dye can cause a feeling of flushing or warmth, in the face or elsewhere. Some people get hives or, rarely, more serious allergic reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies or have 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 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: In some cases, a CT can be used to guide a biopsy needle into a suspected abnormality, such as an abscess. For this procedure, you lie on the CT scanning table while the doctor moves a biopsy needle through the skin and toward the mass. CT scans are repeated until the needle is within the mass. A sample is then removed and sent to the lab to be looked at under a microscope.
PET/CT: Some machines combine the CT scan with a PET scan (PET/CT scan). For a PET scan, glucose (a form of sugar) containing a radioactive atom is injected into the blood. Because cancer cells in the body grow rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. With a PET/CT scan, the doctor can compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.
Magnetic resonance imaging (MRI) scan
Like CT scans, MRI scans make detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A contrast material is often injected into a vein before the scan to better see details. This contrast is not the same as the contrast used for CT scans, but allergic reactions can still occur.
MRI scans are very helpful in looking at the brain and spinal cord, but they are not usually needed in people with AML.
MRI scans take longer than CT scans – often up to an hour. You might have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you may find disturbing. Some places give you headphones or earplugs to help block this noise out.
Ultrasound uses sound waves and their echoes to make pictures of internal organs or masses.
Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver, spleen, and kidneys. (It can’t be used to look inside the chest because the ribs block the sound waves.) It is sometimes used to help guide a biopsy needle into an enlarged lymph node.
For this test, a small, microphone-like instrument called a transducer is usually placed on the skin over the area to be examined (the skin is first lubricated with gel). It gives off sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image on a computer screen.
This is an easy test to have, and it uses no radiation. For most scans, you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.
Last Medical Review: 12/09/2014
Last Revised: 12/09/2014