Myelodysplastic syndromes (MDS) can cause many different signs and symptoms. Patients can have symptoms such as weight loss, fever, and loss of appetite. Of course, these do not occur only with MDS and are more often caused by something other than cancer.

Shortages of one or more types of blood cells can cause most signs and symptoms of MDS:

• Excessive tiredness, shortness of breath, and pale skin can be caused by anemia (shortage of red blood cells).

• Serious infections with high fevers can be caused by leukopenia (not having enough normal white blood cells) and, in particular, by having neutropenia or granulocytopenia (too few mature granulocytes).

• Excessive bruising and bleeding (for example, frequent or severe nosebleeds and/or bleeding from the gums) can be due to thrombocytopenia (not having enough of the blood platelets needed for plugging holes in damaged blood vessels).

If signs and symptoms suggest you may have MDS, the doctors will look at cells from your blood and bone marrow to confirm this diagnosis.

Blood cell counts and blood cell examination: Changes in the number of different blood cell types and the appearance of these cells under the microscope help to diagnose and classify some types of MDS. Patients with MDS will generally have too few red blood cells and may have shortages of white blood cells and blood platelets as well. Patients with RAEB (refractory anemia with excess blasts) can have a small number of myeloblasts in their peripheral (circulating) blood. Myeloblasts normally represent less than 5% of the cells in the bone marrow but should not be present in circulating blood.

In patients with CMML, JMML, or atypical CML, the white blood counts can be very high.

Blood cells from MDS and MDS/MPD patients may also have certain abnormalities in size, shape, or other features that can be seen under the microscope. Although these findings suggest MDS, the doctor cannot make an exact diagnosis without examining a sample of bone marrow cells.

Bone marrow biopsy and aspiration: Bone marrow aspiration involves removing a few drops of bone marrow. During a biopsy, a small cylindrical piece of bone and bone marrow (about 1/16-inch in diameter and 1/2-inch long) is removed. Before this is done, the doctor will inject some local anesthetic to make the bone and skin less sensitive. Both samples generally are taken at the same time from the back of the pelvic bone. These tests are used first for diagnosis and classification and may be repeated later to tell if the MDS or MDS/MPD is responding to therapy or is transforming into an acute leukemia.

A pathologist (a doctor specializing in the diagnosis of diseases using laboratory tests) examines the bone marrow samples (from aspiration and biopsy) under a microscope. A hematologist (a doctor specializing in medical treatment of diseases of the blood and blood-forming tissues ) or an oncologist (a doctor specializing in medical treatment of cancer) usually reviews these as well.

The doctors will look at the size and shape of the cells and determine whether the red cells contain iron particles or the other cells contain granules (microscopic collections of enzymes and other chemicals that help white blood cells to fight infections). The percentage of marrow cells that are blasts is particularly important. Blasts are produced by bone marrow stem cells and eventually develop into mature blood cells. In MDS, the blasts do not mature properly, so there may be too many blasts and not enough mature cells.

For a diagnosis of MDS, a patient must have less than 20% blasts in the bone marrow. A patient who has more than 20% blasts in the bone marrow is considered to have acute leukemia.

Cytochemistry: After cells from a circulating blood sample or bone marrow sample are placed on glass microscope slides, they are exposed to stains (dyes) that are attracted to certain chemicals present in only some types of MDS or MDS/MPD cells. For example, one stain causes the granules inside the cells to appear as black spots when viewed under the microscope, but it does not cause other types of cells to change colors.

Flow cytometry: This technique is sometimes used to examine the cells from bone marrow and blood samples. It is very accurate in determining the exact type of MDS or MDS/MPD or leukemia. A sample of cells is treated with special antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of cells. If the sample contains those cells, the laser will cause them to give off light. The instrument detects the light, and a computer counts the cells. This test may not be needed for all patients.

Immunocytochemistry: As in flow cytometry, cells from the bone marrow aspiration or biopsy sample are treated with special antibodies. 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 MDS or leukemia from one another and from other diseases.

Cytogenetics: Normal human cells contain 46 chromosomes (23 pairs). They are composed of DNA and control cell growth and metabolism. In some cases of MDS and MDS/MPD, one or more chromosomes or parts of chromosomes may be missing. In other cases, MDS cells may have too many copies of one or more chromosomes or translocations, where portions of chromosomes may trade places with each other.

Cytogenetic testing usually takes around 3 weeks because the MDS cells need time to grow in laboratory dishes before their chromosomes can be viewed under the microscope. The results of cytogenetic testing are written in a shorthand form that describes which chromosome changes are present. For example:

• A deletion, written as -7 or -5, for example, indicates chromosome 7 or 5 has been lost. Usually only part of a chromosome is lost. There are 2 parts to a chromosome, called p and q. Thus the typical loss of the q part of chromosome 5 is called 5q- or del(5q).

• An addition, written as +8, for example, happens when a chromosome has been duplicated, and too many copies of it are found within the cell.

Molecular genetic studies: DNA tests of MDS cells, called FISH, can more quickly reveal most of the translocations that are visible under a microscope in cytogenetic tests. DNA tests can also find some translocations involving parts of chromosomes too small to be seen with usual cytogenetic testing. This sophisticated testing is not needed to make a diagnosis in most cases of MDS, but is useful in determining a person's outlook. Last Revised: 12/07/2006