Diagnosis
of Leukemia
If signs and symptoms suggest that a patient has 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 guide treatment.
Blood cell counts and blood cell examination:
Changes in the numbers of
different types of blood cells and the appearance of these cells under the
microscope often help diagnose leukemia. Most patients with AML have
too many white cells in their blood, not enough red blood cells, and not enough
platelets. In addition, many of these white blood cells will be blasts, an
immature blood-forming cell normally found only in the bone marrow. These
immature cells do not function normally. Even though these findings suggest
leukemia, usually the disease cannot be diagnosed without getting a sample of
bone marrow cells.
Bone marrow aspiration and biopsy:
The bone marrow sample
is taken from the pelvic (hip) bone. The patient lies on his or her
side and the doctor feels the bones at the top of the buttocks. The
area is cleaned with a special soap. Before the sampling, the doctor
injects a local anesthetic, usually lidocaine, into the back of the
pelvic bone about an inch or two from the middle of the back. This
causes some very brief stinging. In some cases, the patient can choose
to receive other medicines to reduce pain during the procedure.Once
this has had a few moments to take effect, the doctor makes a small cut
so he or she can insert a needle, which is about half as wide as a
pencil and has a handle on one end that the doctor holds while moving
it into the bone. The needle is moved through the bone with a twisting
motion. In bone marrow aspiration, a syringe is used to suck out
a small amount of liquid bone marrow (about 1
teaspoon). Sometimes the needle going into the bone is painful, but it only
lasts a short time. The sucking out is often painful or at least uncomfortable for a brief moment.
Usually this is followed by a bone marrow biopsy in the same area. The
doctor carefully moves the needle further into the bone marrow to collect a
second sample called a core biopsy.
This contains a small solid piece of bone and marrow (about 1/16 inch
in diameter and � inch long) and is removed with a slightly larger
needle. You may also feel some pressure as the doctor removes the
marrow specimen. After the biopsy needle is pulled out, this solid
sample is pushed out of the needle with a wire so that it can be
examined under a microscope. You will have pressure held against your
buttock at the biopsy site for a few minutes and a pressure dressing
applied to help prevent bleeding. this is especially important for
patients who might bleed more because of low platelet counts.
These bone marrow tests are used to diagnose leukemia and, later, to tell if
the leukemia is responding to treatment.
Blood chemistry tests:
These tests measure the amounts of certain
chemicals in the blood but are not used to diagnose leukemia. In patients
already known to have leukemia, these tests help detect liver or kidney problems
due to damage caused by the spread of leukemic cells or from the side effects
of certain chemotherapy drugs. These tests also help determine whether treatment
is needed to correct abnormally low or high blood levels of certain minerals.
Lumbar puncture (spinal tap):
In this procedure, a small needle is placed
into the spinal cavity in the lower back (below the level of the spinal cord) to
withdraw cerebrospinal fluid (CSF) to be examined for leukemia cells. This is
not routinely done for patients with AML.
Lab Tests Used to Diagnose and Classify Acute Myeloid Leukemia
One or more of the following lab tests may be used.
Routine microscopic exam:
Any samples taken (blood, bone marrow, or
cerebrospinal fluid) are examined under a microscope by a pathologist (doctor
specializing in diagnosis of disease by laboratory tests) and are often also
reviewed by the patient's hematologist/oncologist (doctor specializing in
medical treatment of cancer and blood diseases).
Based on the bone marrow cells� size, shape, and granules, doctors can
classify them into specific types. A key element of this cell classification is
whether the cells appear mature (resembling normal cells of circulating blood)
or immature (lacking features of normal circulating blood cells). The most
immature cells are called blasts.
The percentage of cells in the bone marrow that are blasts is particularly
important. Having at least 20% blasts in the marrow is generally required for a
diagnosis of acute myeloid leukemia. IAMLcan 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%. In order for a patient to be considered to
be in remission after treatment, the blast percentage must be no higher than 5%.
Sometimes this examination does not provide a definite answer, and other lab
tests are needed.
Cytochemistry:
Cytochemistry studies involve placing cells from the
sample on glass microscope slides, then exposing them to chemical stains (dyes)
that are attracted to or react with only some types of leukemia cells. These
stains cause color changes that can be seen only under a microscope. For
example, one stain distinguishes AML from acute lymphocytic leukemia (ALL). 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 examine the cells from
bone marrow and blood samples. It is very accurate in determining the exact type
of leukemia.
Leukemia cells can be distinguished by the kinds of molecules on their
surface. A sample of cells is treated with special antibodies which stick to the
cells only if certain molecules are present on their surfaces. The cells are
then passed in front of a laser beam. If the sample contains cells that now
have antibodies attached to them, the laser will cause them to give off light,
which is measured and analyzed by a computer. Groups of cells can be separated
and counted by these methods.
Immunocytochemistry:
During this test, as in flow cytometry, cells from
the bone marrow aspiration or biopsy sample are treated with special antibodies
that react only to certain molecules. But instead of using a laser and computer
for analysis, the sample is treated so that certain types of cells change color.
The color change can be seen only under a microscope. Like flow cytometry, it is
helpful in distinguishing different types of leukemia from one another and from
other diseases.
Cytogenetics:
These tests involve looking at a cell�s chromosomes under a
microscope. Normal human cells contain 46 chromosomes, pieces of DNA that
control cell growth and metabolism.
In certain types of leukemia, 2 chromosomes may exchange 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 helps to identify
certain types of AML and is important in determining the outlook for the
patient.
The testing usually takes about 3 weeks, because the leukemic cells must grow
in laboratory dishes for a couple of weeks before their chromosomes are ready to
be viewed 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(1;2), for example, means a part of
chromosome 1 is now located on chromosome 2 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.
Molecular genetic studies:
Special tests of leukemia cell DNA can also
find most translocations that are visible under a microscope in cytogenetic
tests, as well as some translocations too small to be seen with usual
cytogenetic testing under a microscope.
This sophisticated testing, called FISH (fluorescent in situ hybridization), is helpful in classifying leukemia because many
subtypes of AML have distinctive translocations. Information about these
translocations may be useful in predicting how the patient will respond to treatment.
These tests may also be used after treatment to find small numbers of
leukemia cells that can be missed under a microscope.
Gene-expression profiling: This is a new
experimental technique that is being used for many cancers. It produces
a pattern of the genes that are in the cancer cells. This creates a
unique fingerprint that can distinguish different kinds of cancer
cells. It is also being used to classify subtypes of AML into different
risk categories. This will add to the information that comes from the
standard molecular genetic studies that only look for specific genetic
abnormalities. The exams and tests may include the following:
- Physical exam — The
doctor checks for swelling of the lymph nodes, spleen, and liver.
- Blood tests — The lab checks the level of blood cells. Leukemia
causes a very high level of white blood cells. It also causes low levels of
platelets and hemoglobin, which is
found inside red blood cells. The lab also may check the blood for signs that
leukemia has affected the liver and kidneys.
- Biopsy — The
doctor removes some bone marrow from the hipbone or another large bone. A
pathologist examines the sample under a microscope.
The removal of tissue to look for cancer cells is called a biopsy. A biopsy
is the only sure way to know whether leukemia cells are in the bone marrow.
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Doctors Hub
There are two ways the doctor can obtain bone marrow. Some patients will have
both procedures:
- Bone marrow aspiration: The doctor uses a needle to remove samples of bone marrow.
- Bone marrow biopsy: The doctor uses a very thick needle to remove
a small piece of bone and bone marrow.
Local anesthesia helps to make the patient more comfortable.
- Cytogenetics — The lab looks at the chromosomes of cells from samples of peripheral
blood, bone marrow, or lymph nodes.
- Spinal tap — The doctor removes some of the cerebrospinal fluid
(the fluid that fills the spaces in and around the brain and spinal cord). The
doctor uses a long, thin needle to remove fluid from the spinal column. The
procedure takes about 30 minutes and is performed with local anesthesia. The
patient must lie flat for several hours afterward to keep from getting a
headache. The lab checks the fluid for leukemia cells or other signs of
problems.
- Chest x-ray — The
x-ray can reveal signs of disease in the chest.
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