The diagnosis of MDS ultimately depends on microscopic examination of your bone marrow and the analysis of damage to the chromosomes or DNA of bone marrow cells. For this exam, you'll need to have a bone marrow biopsy. But before your doctor will recommend this biopsy, he or she will ask about your symptoms and medical history, perform a physical exam, and do some testing. However, MDS tends to produce nonspecific symptoms and the bone marrow biopsy will be necessary for diagnosis.
The diagnosis and prognosis of MDS includes the following:
Your doctor will ask about your symptoms and medical history. Your answers may point in any of three directions: to your red blood cells that suggest anemia, to your blood clotting mechanisms if you are bruising or bleeding, or to your immune system if you are having worrisome infections. Rarely, patients may present during an acute infection that signifies an infection-fighting deficit. In this case, a persistent sore throat or nonhealing infection elsewhere may be the first sign of difficulty.
There may be little or nothing to discover from your physical exam. You may have bruising, an active infection somewhere in your body, or findings such as pale skin and a rapid heartbeat that suggest anemia. Your spleen, lymph glands, and/or liver may be enlarged.
Your first set of laboratory tests will probably be very general and may include the following:
- Blood chemistry and urinalysis
—A sample of your blood and a sample of your urine are tested. These tests will be done as a routine and may reveal abnormalities, but they will not be specific.
- Complete blood count (CBC)
—A blood count may reveal multiple abnormalities and be the basis for further investigations. Your blood will be analyzed on an automated cell counter to determine the number and type of white blood cells, red blood cells, and platelets.
- Peripheral blood smear
—Your blood sample will be examined in the laboratory under a microscope. If you have MDS, some or all of your blood cells will be either abnormal or deformed when examined under magnification. The most common abnormality is one of quantity; that is, patients with MDS most often have low amounts of one or more blood cell types. Occasionally the number may be increased and the relative counts may fluctuate over time.
If there are abnormalities in your blood tests, your doctor will likely refer you to a hematologist (a physician who specializes in disorders of the blood), who will do a bone marrow biopsy.
For this procedure, you'll be given local anesthesia, then a needle is inserted into the back of the pelvis to the right or left of the midline, or your sternum (breastbone). A sample of the bone marrow tissue is suctioned out for testing in two parts. The first part is called the aspiration where 1-2 teaspoons of bone marrow liquid is removed. The second part involves removing a small core of tissue (biopsy) to examine the architecture surrounding the cells. The exam of the bone marrow tissue will not only confirm a diagnosis, it will also characterize the type of MDS and provide treatment and prognostic information. Some of the aspiration material is also sent for molecular and chromosome analysis. This procedure may cause some discomfort, but it is brief.
Cytology is the study of cells. The cytology of cancer cells differs significantly from normal cells, and physicians use the unique cellular features seen on biopsy samples to determine the diagnosis and assess the prognosis of a cancer. With MDS, the bone marrow produces enough cells, but the cells are abnormal and unable to function properly. Any or all of the cell types in the marrow may show abnormalities that will confirm your diagnosis with precision. However, a few cell types are critical to the final classification of the several forms of MDS:
- A “blast” is the most immature form of any of the cell types. More than 30% blasts in the bone marrow traditionally signifies the presence of acute leukemia.
- A “ringed sideroblast” is from the red blood cell series.
Staging is the process by which physicians determine the prognosis of a cancer that has already been diagnosed. Staging is essential for making treatment decisions (eg, surgery vs. chemotherapy). Several features of the cancer are used to arrive at a staging classification, the most common being the size of the original tumor, extent of local invasion, and spread to distant sites (metastasis). Low staging classifications (0-1) imply a favorable prognosis, whereas high staging classifications (4-5) imply an unfavorable prognosis.
MDS is not a cancer, therefore it is not staged according to standard cancer staging paradigms. Instead, MDS is classified into five separate entities based on the appearance of the bone marrow:
- Refractory anemia with ringed sideroblasts (RARS)
- Refractory anemia (RA)
- Chronic myelomonocytic leukemia (CMML)
- Refractory anemia with excess blasts (RAEB)
- Refractory anemia with excess blasts in transformation (RAEB-t)
Each of these types has criteria for definition, including the presence of ring sideroblasts and the percentage of cells that are called blasts. In general, the greater the damage, the more the chromosomal damage, and the greater the number of blasts in the bone marrow, the greater the chance of progressing to acute leukemia.
Prognosis is a forecast of the probable course and/or outcome of a disease or condition. Prognosis is most often expressed as the percentage of patients who are expected to survive over five or ten years. Cancer prognosis is a notoriously inexact process. This is because the predictions are based on the experience of large groups of patients suffering from cancers at various stages. Using this information to predict the future of an individual patient is always imperfect and often flawed, but it is the only method available. Prognoses provided in this monograph and elsewhere should always be interpreted with this limitation in mind. They may or may not reflect your unique situation.
This table gives the occurrence rate and prognosis for the five types of MDS. As you can see, the survival rate is largely determined by the rate of transformation to acute leukemia.
Occurrence Rate and Prognosis for the Five Types of MDS| Type | % of MDS cases | Median survival (range) in months | % transformation (range) to acute leukemia |
|---|
| RARS | 24 | 49 (21-76) | 5 (0-15) |
| RA | 28 | 37 (19-64) | 11 (0-20) |
| CMML | 16 | 22 (8-60) | 20 (3-55) |
| RAEB | 23 | 9 (1-50) | 23 (11-50) |
| RAEB-t | 9 | 6 (5-12) | 48 (11-75) |
There is some debate over this classification because there are no clear distinctions among many of the individual entities and the leukemias. All of these marrow diseases merge into one another so that many distinctions are arbitrarily defined. Classification systems will continue to evolve.
