Myelodysplastic syndromes (MDS) are blood cancers where the bone marrow, the body’s blood cell factory, produces faulty, immature, or short-lived blood cells. This results in a shortage of healthy, mature blood cells, a condition known as ineffective hematopoiesis. Diagnosing MDS requires a comprehensive, multi-step process, integrating clinical observations with detailed laboratory and genetic findings. The diagnosis confirms the disease, rules out other conditions, and classifies the specific MDS type, which is crucial for determining treatment.
Initial Suspicion and Blood Screening
The first indication of MDS often arises from non-specific symptoms related to the lack of healthy blood cells. Common complaints include fatigue and shortness of breath due to anemia (low red blood cells). Patients may also experience frequent infections from a low white blood cell count, or easy bruising and tiny red spots (petechiae) due to low platelet counts.
These symptoms prompt a healthcare provider to order a Complete Blood Count (CBC) with a differential. The CBC measures red cells, white cells, and platelets, typically revealing cytopenias—low counts in one or more of these three major blood cell lines. The differential count breaks down the white blood cells, which may show an abnormal distribution of cell types.
A peripheral blood smear is also standard, where a drop of blood is examined under a microscope. The pathologist looks for morphological evidence of dysplasia, meaning the blood cells have an abnormal size, shape, or appearance. For instance, red blood cells might be abnormally large (macrocytic), suggesting a manufacturing defect in the bone marrow. This initial blood work raises suspicion, but a definitive diagnosis requires examining the bone marrow itself.
Bone Marrow Aspiration and Biopsy
The diagnosis of Myelodysplastic Syndromes requires a bone marrow exam, involving both an aspiration and a biopsy. This procedure is typically done on the posterior iliac crest (hip bone) after the area is numbed.
The bone marrow aspiration uses a hollow needle to draw out a liquid sample, which is analyzed for detailed cellular morphology. This aspirate is essential for accurately counting the percentage of blasts, which are immature blood cells. An increased percentage of blasts, normally present in very low numbers, is a defining feature of some MDS subtypes.
The bone marrow biopsy uses a specialized needle to remove a small, solid core of tissue. This sample is crucial for assessing the overall cellularity of the marrow—whether it is hypercellular or hypocellular—and evaluating the marrow structure. Pathologists examine the biopsy for dysplasia in megakaryocytes (platelet precursors). Both the aspirate and biopsy provide a complete picture of blood cell production.
Genetic and Molecular Analysis
Bone marrow samples undergo specialized testing to look for genetic abnormalities characterizing MDS. Cytogenetics, or karyotyping, examines the chromosomes for large-scale changes. About 50% of MDS patients have a detectable chromosomal abnormality, such as the loss of part of chromosome 5 (del(5q)), the loss of chromosome 7, or the gain of chromosome 8 (trisomy 8).
Fluorescence In Situ Hybridization (FISH) uses fluorescent probes to highlight specific chromosomal regions, detecting abnormalities when karyotyping is inconclusive. These large chromosomal changes help confirm the diagnosis and are integrated into prognostic scoring systems.
Next-Generation Sequencing (NGS) detects smaller gene mutations not visible through traditional cytogenetics. MDS is associated with mutations in over 40 genes, and NGS panels test for recurrently mutated genes such as SF3B1, TET2, ASXL1, and TP53. The presence of these mutations provides crucial diagnostic and prognostic information, helping to define specific subtypes and predict disease course.
Determining MDS Subtype and Risk Level
All information from blood counts, morphology, and genetic analysis is synthesized to classify the specific MDS subtype. Classification systems, such as those from the World Health Organization (WHO), categorize MDS based on the percentage of blasts in the bone marrow, the presence of dysplasia, and specific genetic findings. Examples include MDS with isolated del(5q), MDS with ring sideroblasts, or MDS with excess blasts (MDS-EB), where the blast percentage is between 5% and 19%.
The collected data are also used for risk stratification, predicting the disease’s likely behavior and prognosis. The Revised International Prognostic Scoring System (IPSS-R) is the most widely used method. The IPSS-R generates a score by factoring in five variables: the percentage of blasts, the severity of cytopenias, and the specific cytogenetic abnormalities found.
This calculation places the patient into one of five distinct risk categories: Very Low, Low, Intermediate, High, or Very High. This risk level predicts overall survival and the likelihood of progression to acute myeloid leukemia (AML). Risk stratification directly informs the treatment strategy, guiding whether supportive care or more aggressive intervention is needed.