Acute myeloid leukemia (AML) can cause many different signs and symptoms, but some occur more commonly with certain subtypes.

Generalized symptoms: Patients with AML often have several non-specific (generalized) symptoms. These can include weight loss, fatigue, fever, and loss of appetite. Of course, these are not specific to AML, and more often are caused by something other than cancer.

Shortage of 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 tiredness (fatigue), weakness, headache, feeling cold, dizzy, or lightheaded, 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). Although patients with AML may have high white blood cell counts due to excess numbers of leukemia cells, 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.

Bone or joint pain: Some patients have bone pain or joint pain caused by the buildup of leukemia cells in bones or joints.

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, and 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 appear swollen.

Medical History and Physical Exam

Most symptoms of AML can also be seen in other problems like infections. For this reason, an accurate diagnosis is crucial.

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.

A thorough physical exam will likely include evaluation of the eyes, mouth, skin, lymph nodes, liver and spleen, and the nervous system. It will also include looking 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.), the doctor will likely test the patient's blood counts. If the results suggest leukemia may be the cause, the doctor may refer the patient to a cancer doctor, who may run one or more of the tests described below.

Types of Specimens Used to Test for Acute Myeloid Leukemia

If signs and symptoms suggest that a patient may have leukemia, the doctor will need to check samples of cells from the patient's 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: Blood samples for tests for AML are generally taken from a vein in the arm.

Bone marrow samples: Bone marrow samples are obtained from a bone marrow aspiration and biopsy - two tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the sternum (breast bone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the area, the skin over the hip 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 (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. The biopsy 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 therapy.

Lumbar puncture (spinal tap): This test looks for leukemia cells in the cerebrospinal fluid (CSF), which is the liquid that surrounds the brain and spinal cord.

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 near the spine. A small 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 used to diagnose AML and/or to determine the specific subtype of AML.

Blood cell counts and blood cell examination: These tests look at how the different types of blood cells 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"), immature blood-forming cells that are not normally found in the bloodstream. These immature cells do not function like normal, mature white blood cells. Even though these findings may suggest leukemia, 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 can detect liver or kidney problems, abnormal levels of certain minerals in the blood, or problems with the clotting ability of the blood .

Routine microscopic exam: Samples of blood, bone marrow, or CSF are looked at under a microscope by a pathologist (a doctor specializing in diagnosing diseases with lab tests) and may be reviewed by the patient's hematologist/oncologist (a doctor specializing in cancer and blood diseases). Based on the cells' size, shape, and other traits, doctors can classify them into specific cell types. A key element of this classification is whether the cells look like normal cells of circulating blood (mature) or lack features of normal blood cells (immature). The most immature cells are called blasts.

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 acute myeloid leukemia. AML can also be diagnosed if the blasts have a chromosome change that occurs only in a specific type of AML, even though the blast percentage doesn't reach 20%. Sometimes the leukemic blasts look similar to normal immature cells in the bone marrow. However, under normal circumstances, blasts are never more than 5% of bone marrow cells. In order for a patient to be considered to be in remission after treatment, the blast percentage must be no higher than 5%.

These additional tests are used to confirm the diagnosis of AML.

Cytochemistry: Cytochemistry tests involve exposing cells 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: This technique is often used to look at the cells from bone marrow and blood samples. It is very accurate 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.

Related tests, called immunohistochemistry tests, can be used to detect these substances when viewing cells 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.

Cytogenetics: These tests examine a cell's chromosomes (long strands of DNA) under a microscope. Normal human cells contain 23 pairs of chromosomes, each of which is a certain size and stains 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, such as inversions, deletions, or additions, are also possible. Recognizing these changes can help identify certain types of AML and may be important in determining the outlook for the patient.

The testing 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.

Fluorescent in situ hybridization (FISH): This procedure is similar to cytogenetic testing. It can find most 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. It uses special fluorescent dyes that only attach to specific parts of particular chromosomes. 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.

Very sensitive DNA tests such as polymerase chain reaction (PCR) tests can also find translocations 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

Imaging tests produce pictures of the inside of the body. Because leukemia does not usually form visible tumors, imaging tests are of limited value. There are several imaging studies 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 studies 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.

X-rays: 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, as does 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.

Often after the first set of pictures is taken, you will receive an intravenous (IV) injection of a contrast dye, or you may be asked to drink a solution of contrast material, to better outline blood vessels and internal organs. A second set of pictures is then taken.

The IV injection of 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 lay 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 fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about ½-inch long and less than 1/8-inch in diameter) is then removed to be looked at under a microscope.

Magnetic resonance imaging (MRI) scan: 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. Not only does this create images of cross-sectional slices of the body like a CT scanner, it can also produce images of slices that are parallel with the length of your body. A contrast material might be injected, just as with CT scans, but is used less often. MRI scans are very helpful in looking at the brain and spinal cord.

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 upset people with a fear of enclosed spaces. Newer, "open" MRI machines can help with this if needed. The MRI machine makes loud buzzing noises that you may find disturbing. Some places provide headphones to block this out.

Ultrasound: Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. For this test, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with oil). 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 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. 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: One of these tests may be useful if a patient has bone pain that might be due to either bone infection or cancer involving 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, x-rays, CTs, or MRIs of the affected area can be done to get a more detailed look. If leukemia is a possibility, a biopsy of the area may be needed to confirm this.