Tests for Myelodysplastic Syndromes (MDS)

Some people have  signs or symptoms  that suggest they might have a myelodysplastic syndrome (MDS). For other people, MDS might be suspected because of the results of blood tests that were done for another reason.

In either case, if MDS is suspected, you will likely need tests to look at your blood and bone marrow cells to see if you have MDS or some other health condition. If MDS is found, other tests will also be done to learn more about it.

Medical history and physical exam

If you have symptoms, your health care provider will want to get your medical history, focusing on the symptoms and when they began. They might also ask about any other health problems you have, as well as about possible risk factors for MDS or related diseases such as leukemia.

You will also be examined for possible causes of your symptoms. The doctor may check 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.

Complete blood count and peripheral blood smear

The  complete blood count (CBC)  is a test that measures the levels of red blood cells, white blood cells, and platelets in your blood. The CBC is often done with a  differential count  (or “diff”), which is a count of the different types of white blood cells in the blood sample.

For a blood  smear, some of your blood is smeared on a slide to see how the cells look under the microscope.

People with MDS often have too few red blood cells (anemia). They may have shortages of white blood cells and blood platelets as well.

People with some types of MDS might also have myeloblasts (or blasts) in the blood. These are very early forms of blood cells that are normally found only in the bone marrow. Blasts aren’t normally in the blood , so if they’re found there it’s often a sign of a bone marrow problem. Blood cells in people with MDS may also have certain abnormalities in size, shape, or other features that can be seen with a microscope.

Blood abnormalities may suggest a person has MDS, but a sample of bone marrow must be looked at as well before a diagnosis of MDS can be made.

Other blood tests

The doctor may also order other tests to check for other possible causes of low blood counts. For example, low levels of iron, vitamin B12, or folate can cause anemia. If one of these is found to be abnormal, a diagnosis of MDS is much less likely.  

Bone marrow tests

Bone marrow samples are taken by a  bone marrow aspiration and biopsy, tests that are usually done at the same time. The samples usually come from the back of the pelvic (hip) bone.

These tests are done first to diagnose and help classify MDS. They may also be done again later to tell if the MDS is responding to treatment or is transforming into an acute leukemia.

For a  bone marrow aspiration, the skin over the hip and the surface of the bone is numbed with local anesthetic, which may sting or burn briefly. 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 people 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 put into the bone. The biopsy may also cause some brief pain. Once the biopsy is done, pressure will be put on the site to help prevent bleeding.

Lab tests of bone marrow or blood samples

Different types of lab tests might be done on blood or bone marrow samples to help diagnose MDS.

Routine cell exams by microscope

Samples of bone marrow and/or blood are looked at with a microscope by a pathologist (a doctor specializing in lab tests). Other doctors, such as a hematologist (a doctor who treats diseases of the blood) might review these as well. They will look at the size, shape, and other features  of the cells, especially the white blood cells.

The percentage of cells in the bone marrow or blood that are  myeloblasts (often just called blasts),  which are very early forms of white blood cells, is particularly important. For example, as part of the diagnosis of MDS, a person must have less than 20% blasts in the bone marrow and blood. A person with more than 20% blasts is considered to have  acute myeloid leukemia (AML).

Cytochemistry

Cytochemistry tests expose cells to chemical stains (dyes) that react with only some types of cells. These stains cause color changes that can be seen with a microscope, which can help the doctor determine what types of cells they are.

Flow cytometry and immunohistochemistry

For both flow cytometry and immunocytochemistry (IHC), samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For IHC, the cells are then looked at with a microscope to see if the antibodies stuck to them (meaning they have these proteins); for flow cytometry a special machine is used.

These tests are used for immunophenotyping or classifying cancer cells according to the substances (antigens) on their surfaces. MDS cells can have different antigens, so this can sometimes be helpful in determining what type of MDS a person has.

Chromosome and gene tests

Some tests look at the chromosomes inside the cells. Chromosomes are long strands of DNA that contain our genes. Normal human cells contain 23 pairs of chromosomes, and each pair varies in size and appearance.

MDS cells sometimes have chromosome changes that can be seen by a microscope or found with other tests. Recognizing these changes can help identify certain types of MDS and might also be important in determining a person’s outlook and treatment options.

Cytogenetics (karyotyping):  In this test, the cells are looked at under a microscope to see if the chromosomes have any abnormalities. A drawback of this test is that it usually takes about 2 to 3 weeks because the cells must grow in lab dishes for a couple of weeks before their chromosomes can be viewed.

The results of cytogenetic testing are written in a shorthand form that describes the chromosome changes. For example:

• A  translocation  means parts of two chromosomes have traded places with each other. For example, if chromosomes 3 and 21 have swapped pieces, it would be written as t(3;21).
• An  inversion, written as inv(3), for example, means that part of the chromosome 3 is now in reverse order but is still attached to the chromosome.
• A  deletion, written as del(5q), for example, indicates part of chromosome 5 has been lost.
• An  addition  or  duplication, such as +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.

Certain chromosome changes in MDS cells can help predict the likely course of MDS. For example, a deletion of a part of chromosome 5, or del(5q), usually predicts a better outcome (as long as there is no more than one other chromosome change, and it isn't a loss of part of chromosome 7).

Not all chromosome changes can be seen with a microscope. Other lab tests can often detect these changes.

Fluorescent in situ hybridization (FISH):  This test looks more closely at cell DNA using fluorescent dyes that only attach to specific gene or chromosome changes. An advantage of FISH is that it doesn’t require actively dividing cells, so it can usually provide results within a couple of days.

FISH can find the chromosome changes (such as translocations) that are visible with a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

Polymerase chain reaction (PCR):  This is a very sensitive test that can also find some chromosome changes too small to be seen under a microscope. It can be helpful in finding gene changes that are in only a few cells, making it good for finding small numbers of abnormal cells in a sample (like after treatment).

Other molecular and genetic tests

Other types of lab tests can also be done on the samples to look for specific gene or other changes in the MDS cells. This is sometimes referred to as biomarker testing.

Some of the changes found on these tests can help doctors learn more about the type of MDS a person has, how quickly it’s likely to progress, and even if some treatments are likely to be helpful. For example, the MDS cells are often tested for changes (mutations) in genes such as IDH1. People whose MDS cells have changes in this gene are more likely to be helped by treatment with certain  targeted therapy drugs.