How is acute myeloid leukemia diagnosed?
Certain signs and symptoms might suggest that a person may have acute myeloid leukemia (AML), but tests are needed to confirm the diagnosis.
Signs and symptoms of acute myeloid leukemia
Acute myeloid leukemia (AML) can cause many different signs and symptoms. Some occur more commonly with certain subtypes.
Patients with AML often have several non-specific (generalized) symptoms. These can include weight loss, fatigue, fever, night sweats, and loss of appetite. Of course, these are not specific to AML, and more often are caused by something other than leukemia.
Problems caused by low blood cells
Most signs and symptoms of AML result from a shortage of normal blood cells, which happens when the leukemia cells crowd out the normal blood-making cells in the bone marrow. As a result, people do not have enough normal red blood cells, white blood cells, and blood platelets. These shortages show up on blood tests, but they can also cause symptoms.
- Anemia is a shortage of red blood cells. It can cause a person to feel tired, weak, cold, dizzy, or lightheaded, and can cause headaches and shortness of breath.
- A shortage of normal white blood cells (leukopenia) increases the risk of infections. A common term you may hear is neutropenia, which refers specifically to low levels of neutrophils (a type of granulocyte). Patients with AML may have high white blood cell counts due to excess numbers of leukemia cells, but these cells do not protect against infection the way normal white blood cells do. Fevers and recurring infections are some of the most common symptoms of AML.
- A shortage of blood platelets (thrombocytopenia) can lead to excess bruising, bleeding, frequent or severe nosebleeds, and bleeding gums.
Symptoms caused by high numbers of leukemia cells
The cancer cells in AML (blasts) are bigger than normal white blood cells and have more trouble going through tiny blood vessels. If the blast count gets very high, these cells clog up blood vessels and make it hard for normal red blood cells (and oxygen) to get to tissues. This is called leukostasis. Some of the symptoms are like what is seen with a stroke, and include headache, weakness in one side of the body, slurred speech, confusion, and sleepiness. When blood vessels in the lung are affected, patients have problems with shortness of breath. Blood vessels in the eye can be affected as well, leading to blurry vision or even loss of vision. Leukostasis is rare, but it is a medical emergency that needs to be treated right away.
Bleeding and clotting
Patients with a certain type of AML called acute promyelocytic leukemia (APL) may come in with problems with bleeding and clotting. They may have a nose bleed that won’t stop, or a cut that won’t stop oozing. They may also have calf swelling from a blood clot called a deep venous thrombosis (DVT) or chest pain and shortness of breath from a blood clot in the lung (called a pulmonary embolism or PE).
Bone or joint pain
Some patients have bone pain or joint pain caused by the buildup of leukemia cells in these areas.
Swelling in the abdomen
Leukemia cells may collect in the liver and spleen, causing them to enlarge. This may be noticed as a fullness or swelling of the belly. The lower ribs usually cover these organs, but when they are enlarged the doctor can feel them.
Spread to the skin
If leukemia cells spread to the skin, they can cause lumps or spots that may look like common rashes. A tumor-like collection of AML cells under the skin or other parts of the body is called a chloroma or granulocytic sarcoma.
Spread to the gums
Certain types of AML may spread to the gums, causing swelling, pain, and bleeding.
Spread to other organs
Sometimes, leukemia cells may spread to other organs. Spread to central nervous system (brain and spinal cord) can cause headaches, weakness, seizures, vomiting, trouble with balance, facial numbness, or blurred vision. On rare occasions AML may spread to the eyes, testicles, kidneys, or other organs.
Enlarged lymph nodes
In rare cases, AML may spread to lymph nodes. Affected nodes in the neck, groin, underarm areas, or above the collarbone may be felt as lumps under the skin.
Although the symptoms and signs above may be caused by AML, they can also be caused by other conditions. 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 signs or symptoms suggest the possibility of leukemia, the doctor will want to obtain a thorough medical history, including how long symptoms have been present and whether or not there is any history of exposure to risk factors.
During the physical exam, the doctor will likely pay close attention to the eyes, mouth, skin, lymph nodes, liver and spleen, and the 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.), your doctor will test your blood counts. If the results suggest leukemia may be the cause, the doctor may refer you to a cancer doctor, who may run one or more of the tests described below.
Types of samples used to test for acute myeloid leukemia
If signs and symptoms and/or the results of the physical exam suggest you may have leukemia, the doctor will need to check samples of cells from the blood and bone marrow to be sure of the diagnosis. 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 with 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 (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 (about 1/16 inch in diameter and 1/2 inch long) is removed with a slightly larger needle that is twisted as it is pushed down into the bone. This causes a pressure feeling, and rarely 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. They may also be 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. Leukemia can 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 a sample of this fluid is called a lumbar puncture (spinal tap).
For this test, the patient may lie on his side or sit up. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.
A lumbar puncture is not often used to test for AML, unless the patient is having symptoms that could be caused by the spread of leukemia cells into the central nervous system (CNS).
A lumbar puncture is sometimes used to deliver chemotherapy drugs into the CSF to 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 different cells in the blood, such as the red blood cells, the white blood cells, and the 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. These tests look at how the different types of cells in the blood appear under the microscope and how many of them there are. Changes in the numbers and the appearance of these 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 ("blasts"), which are immature blood-forming cells that are not normally found in the bloodstream. These immature cells do not function 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 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 the clotting ability of the blood.
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 cells in the bone marrow or blood that are blasts 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 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 similar to normal immature cells in the bone marrow. But in normal bone marrow, the blast count is 5% or less. In order for a patient to be considered to be in remission after treatment, the blast percentage in the bone marrow must be no higher than 5%.
Sometimes just counting and looking at the cells does not 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 these substances are present on their surfaces. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will cause them to 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. Specific types of leukemia cells have different antigens depending on their cell of origin 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 changes in chromosomes are also possible (see below). Recognizing these changes can help identify certain types of AML and may be important in determining the outlook for the patient.
This test usually takes about 2 to 3 weeks because the leukemia cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be looked at under the microscope.
The results of cytogenetic testing are written in a shorthand form that describes which chromosome changes are present.
- 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 upside down and is now in reverse order but is still attached to the chromosome it originated from.
- A deletion, written as del(7) or -7, for example, indicates part of chromosome 7 has been lost.
- An addition, +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 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 specific changes in chromosomes. It can be used on regular blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.
Polymerase chain reaction (PCR)
This is a very sensitive DNA test that can also find some chromosome changes too small to be seen under a microscope, even if very few leukemia cells are present in a sample.
These tests may also be used after treatment to find small numbers of leukemia cells that may not be visible under a microscope.
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 does not usually form visible tumors, so imaging tests are of limited value. There are several imaging tests that might be done in people with AML, but they are done more often to look for infections or other problems, rather than to look for the leukemia itself. In some 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
The CT scan is a type of x-ray that produces 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).
This test can help tell 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.
Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into detailed images of the part of your body that is being studied.
Before the scan, 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 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 when the pictures are being taken.
In some cases, a CT can be used to guide a biopsy needle precisely into a suspected abnormality, such as an abscess. For this procedure, called a CT-guided needle biopsy, you remain on the CT scanning table while a radiologist moves a biopsy needle through the skin and toward the location of the mass. CT scans are repeated until the needle is within the mass. A sample is then removed 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. The PET/CT scan allows the doctor to 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 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 by the body 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. The contrast material usually does not cause allergic reactions.
MRI scans are very helpful in looking at the brain and spinal cord, but they are not often needed in people with AML.
MRI scans take longer than CT scans -- often up to an hour. You may 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 provide headphones or earplugs to help block this out.
Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. Most often for this test, a small, microphone-like instrument called a transducer is placed on the skin over the area to be examined (the skin is first lubricated with gel). It emits sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image that is displayed on a computer screen.
Ultrasound can be used to look at lymph nodes near the surface of the body or to look for enlarged organs inside your abdomen such as the kidneys, liver, and spleen.
This is an easy test to have done, 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.
Gallium scan and bone scan
These tests are not often done for AML, but they may be useful if a patient has bone pain that might be due to either an infection or cancer involving the bones.
For these tests, the radiologist injects a slightly radioactive chemical into the bloodstream, which collects in areas of cancer or infection in the body. These areas can then be viewed with a special type of camera. The images from these scans are seen as "hot spots" in the body, but they don't provide much detail. If an area lights up on the scan, other imaging tests such as x-rays, CTs, or MRIs may be done to get a more detailed look at the area. If leukemia is a possibility, a biopsy of the area may be needed to confirm this.
Last Medical Review: 03/22/2012
Last Revised: 01/18/2013