How to Diagnose Myelodysplastic Syndromes: A Comprehensive Guide
Myelodysplastic syndromes (MDS) are a diverse group of blood disorders that originate in the hematopoietic stem cells. These conditions are primarily characterized by dysfunctional bone marrow activity, leading to abnormal development of myeloid lineage cells and ineffective blood cell production. As a result, patients often suffer from persistent cytopenias—low levels of red blood cells, white blood cells, or platelets—and face an increased risk of progressing to acute myeloid leukemia (AML). Accurate diagnosis is crucial for timely intervention and improved patient outcomes.
Core Diagnostic Criteria for MDS
To confirm a diagnosis of MDS, clinicians must meet two mandatory criteria along with at least one major criterion. These evidence-based benchmarks help differentiate MDS from other conditions with similar presentations and ensure diagnostic precision.
Essential Criterion 1: Persistent Cytopenia
The first mandatory condition involves documented peripheral blood cytopenia lasting at least four months. This includes:
- Neutrophil count < 1.8 × 10⁹/L (1,800/μL)
- Hemoglobin level < 10 g/dL
- Platelet count < 100,000/μL
However, if early signs such as increased blasts in the blood or specific genetic abnormalities linked to MDS are detected, waiting the full four months is not required. Immediate evaluation and diagnosis can proceed based on these red flags.
Essential Criterion 2: Exclusion of Other Causes
It's critical to rule out other potential causes of low blood counts and dysplasia. This includes secondary factors like vitamin deficiencies (e.g., B12 or folate), exposure to toxins, autoimmune diseases, viral infections (such as HIV or hepatitis), or the effects of chemotherapy. Non-clonal hematologic disorders must also be excluded through thorough clinical assessment, laboratory testing, and sometimes bone marrow imaging.
Major Diagnostic Indicators of MDS
In addition to the two essential criteria, at least one major feature must be present to support an MDS diagnosis. These key indicators reflect the underlying clonal and pathological nature of the disease.
Dysplasia in Bone Marrow Cell Lines
Dysplasia affecting more than 10% of cells in one or more myeloid lineages—erythroid (red cells), granulocytic (white cells), or megakaryocytic (platelet-producing cells)—is a hallmark of MDS. Morphological examination of bone marrow smears under microscopy reveals abnormal size, shape, and maturation patterns within these cell populations, indicating disrupted hematopoiesis.
Presence of Ring Sideroblasts
Another strong indicator is the presence of ring sideroblasts comprising over 15% of nucleated red blood cells in the bone marrow. These iron-laden erythroblasts are identified through Perl's Prussian blue staining and suggest impaired heme synthesis—a common trait in certain subtypes of MDS, particularly MDS-RS (with ring sideroblasts).
Elevated Blast Counts
An increased percentage of immature precursor cells (blasts) in the bone marrow (5–19%) or peripheral blood (2–19%) strongly supports an MDS diagnosis. Blasts are normally rare in circulation, so their elevation signals a disruption in cellular differentiation and raises concern for progression toward leukemia.
Clonal Chromosomal Abnormalities
Detection of recurrent cytogenetic changes via conventional karyotyping or FISH (fluorescence in situ hybridization) provides compelling evidence of clonality. Common abnormalities include deletions in chromosomes 5q, 7q, or 20q, or trisomy 8. These genetic markers not only aid in diagnosis but also play a role in risk stratification and treatment planning.
Diagnosing MDS requires a multidisciplinary approach combining clinical history, laboratory data, morphological analysis, and molecular genetics. Early recognition and accurate classification enable personalized management strategies, including supportive care, immunomodulatory therapy, or stem cell transplantation, ultimately improving survival and quality of life for patients.