Diagnosis of leukemia

Diagnosing leukemia usually begins with a visit to your family doctor or when a routine test suggests a problem with the blood. Your doctor will ask you about any symptoms you have and may do a physical exam. Based on this information, your doctor may refer you to a specialist or order tests to check for leukemia or other health problems.

The process of diagnosis may seem long and frustrating. It’s normal to worry, but try to remember that other health conditions can cause similar symptoms as leukemia. It’s important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of leukemia.

When symptoms are severe, acute leukemia diagnosis may proceed rapidly, with the person admitted to hospital to quickly start treatments.

The following tests are commonly used to rule out or diagnose leukemia. Many of the same tests used to diagnose cancer are used to find out the stage, which is how far the cancer has progressed. Your doctor may also order other tests to check your general health and to help plan your treatment.

Your health history is a record of your symptoms, risk factors and all the medical events and problems you have had in the past. In taking a health history, your doctor will ask questions about a personal history of:

• symptoms that suggest leukemia
• exposure to high doses of radiation
• genetic syndromes, such as Down syndrome, Fanconi anemia, ataxia-telangiectasia or Bloom syndrome
• exposure to benzene
• previous chemotherapy or radiation therapy
• blood disorders
• viral infections

Your doctor may also ask about a family history of leukemia.

A physical exam allows your doctor to look for any signs of leukemia. During a physical exam, your doctor may:

• check your vital signs to see if you have a fever, shortness of breath and rapid heartbeat
• check your skin for bruising and paleness
• feel areas of the neck, underarm (axillary) and groin (inguinal) for any swollen, or enlarged, lymph nodes
• check your mouth for infection, bleeding or swollen gums
• feel your abdomen for enlarged organs
• examine your skeleton for tenderness or pain

Find out more about physical exam.

A CBC measures the number and quality of white blood cells, red blood cells and platelets. Leukemia and other conditions can cause abnormal blood cell counts.

Immature blood cells (called leukemia cells, or blasts) are not normally seen in the blood, so doctors will suspect leukemia if there are blasts or blood cells do not look normal.

Find out more about complete blood count (CBC).

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are functioning and can help find abnormalities. They help doctors find problems with the liver or kidney that are caused by the spread of leukemia cells. They can also help doctors stage leukemia.

Levels of the following chemicals may be higher than normal with leukemia:

• blood urea nitrogen (BUN)
• creatinine
• phosphate
• lactate dehydrogenase (LDH)
• alanine aminotransferase (ALT)
• aspartate aminotransferase (AST)
• uric acid

Find out more about blood chemistry tests.

Tests measure blood clotting factors to see how well the body can clot blood. Abnormal levels of blood clotting factors may occur with leukemia. They are measured using the following tests:

• fibrinogen level
• prothrombin time (PT)
• partial thromboplastin time (PTT)
• international normalized ratio (INR)

Cytochemistry uses stains, or dyes, to identify tissue structures and components in blood or bone marrow cells. Certain stains are attracted to certain substances found in some types of leukemia cells, or blasts. The staining results can be seen under a microscope. Cytochemistry helps doctors determine the type of cells that are present.

Immunophenotyping is the study of proteins expressed by cells. It is used to determine the type or subtype of leukemia.

Immunophenotyping uses a very specific antigen-antibody reaction to identify proteins in tissues or cells. It uses monoclonal antibodies marked with a fluorescent label or specific enzyme label that binds only to specific antigens (proteins). The fluorescent or enzyme label allows doctors to see the leukemia cells (also called blasts).

Immunohistochemistry and flow cytometry are the 2 most common methods used in immunophenotyping for leukemia.

Immunohistochemistry uses a microscope to view the immunoperoxidase labels. It also allows doctors to look at cells and what is around them.

Flow cytometry is a technique used to sort and classify cells using fluorescent labels on their surface. The cells are exposed to a laser, which makes them give off a light. The light is measured and analyzed by a computer. Flow cytometry allows doctors to view many antibodies at the same time and collect data rapidly from thousands of cells in a single sample.

Flow cytometry helps to define unique features of leukemia cells, or blasts. These features can help doctors form a prognosis and measure response to treatment using minimal residual disease (MRD). MRD means that there are blasts in the bone marrow that can’t be found using standard lab tests (such as microscopy), but are found using more sensitive tests (such as flow cytometry or polymerase chain reaction).

Cytogenetics is the analysis of a cell’s chromosomes, including the number, size, shape and how they are arranged.

Cytogenetic karyotyping studies show chromosomal abnormalities, which help doctors confirm that someone has leukemia and find out the type or subtype of leukemia. The results of cytogenetic studies also help doctors plan treatment and predict how well the treatment will work.

Some major chromosomal abnormalities can be found by looking at cells under a microscope. But most changes in DNA need a closer analysis with other molecular studies, including fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR).

Fluorescence in situ hybridization (FISH) is a molecular genetic test used to identify chromosomal abnormalities and other genetic changes in the leukemia cells, or blasts. It uses special DNA probes labelled with fluorescent dyes. FISH is used to tell apart leukemias that look the same but that have different genetic abnormalities and may need to be treated differently.

Polymerase chain reaction (PCR) is a method used to make many copies of a particular gene segment so that it can be tested in the lab. PCR is used to find DNA mutations, inversions or deletions that are linked with certain types of leukemia. It is useful in diagnosing and determining the prognosis for a specific type of leukemia.

During a bone marrow aspiration and biopsy, cells are removed from the bone marrow so they can be tested in a lab. The report from the lab will confirm whether or not there are leukemia cells in the sample and, if so, the type of leukemia.

Find out more about a bone marrow aspiration and biopsy.

A lumbar puncture, or spinal tap, removes a small amount of cerebrospinal fluid (CSF) from the space around the spine to look at it under a microscope. CSF is the fluid that surrounds the brain and spinal cord.

A lumbar puncture is done to see if cancer has spread to the spinal fluid.

Find out more about a lumbar puncture.

A lymph node biopsy is a type of surgical biopsy. It is called an excisional biopsy because the lymph node is completely removed. Sometimes the lymph node cannot be completely removed; instead a portion of the lymph node is removed as a core biopsy. Doctors (pathologists) then look at the lymph node under a microscope to find out if there are cancer cells in it, identify the type of cancer and find out how quickly the cancer cells are growing.

Find out more about a surgical biopsy.

An x-ray uses small doses of radiation to make an image of the body’s structures on film. It is used to look for:

• enlarged lymph nodes in the centre of the chest (called mediastinal lymph nodes)
• enlarged thymus gland
• buildup of fluid between the lungs and the walls of the chest (called pleural effusion)
• lung infection (called pneumonia)

Find out more about x-ray.

A computed tomography (CT) scan uses special x-ray equipment to make 3-D and cross-sectional images of organs, tissues, bones and blood vessels inside the body. A computer turns the images into detailed pictures.

A CT scan may be used to look at the spleen and liver to see if they are larger than normal, or enlarged. It can also be used to check if lymph nodes around the heart, near the trachea (windpipe) or in the back of the abdomen are enlarged.

Find out more about CT scan.

Magnetic resonance imaging (MRI) uses powerful magnetic forces and radiofrequency waves to make cross-sectional images of organs, tissues, bones and blood vessels. A computer turns the images into 3-D pictures.

MRI is most often used when doctors think that the leukemia has spread to the brain.

Find out more about MRI.

Ultrasound uses high-frequency sound waves to make images of structures in the body. It is used to see if internal organs, such as the kidneys, liver or spleen, have been affected by leukemia.

Find out more about ultrasound.

To make the decisions that are right for you, ask your healthcare team questions about diagnosis.