How to diagnose Myelodysplastic Syndromes (MDS) in an adult patient with a history of exposure to chemotherapy, radiation, or certain chemicals, presenting with symptoms such as anemia, recurrent infections, or bleeding, using peripheral blood?

Diagnosing MDS from Peripheral Blood

Peripheral blood smear examination is mandatory but insufficient alone for MDS diagnosis—it serves as a critical screening tool that must be followed by bone marrow examination, cytogenetics, and clinical correlation to confirm the diagnosis. 1, 2

What to Look for on Peripheral Blood Smear

The peripheral blood smear provides two essential diagnostic elements: evaluation of dysplastic features across cell lines and enumeration of circulating blasts. 2

Erythroid Dysplasia

• Anisocytosis (variation in red cell size) 1, 2
• Poikilocytosis (variation in red cell shape) 1, 2
• Basophilic stippling 1, 2

Myeloid Dysplasia

• Pseudo-Pelger-Huët anomaly: granulocytes with nuclear hypolobation appearing as bilobed or monolobed nuclei resembling pince-nez eyeglasses 1, 2
• Cytoplasmic hypogranulation or complete degranulation of granulocytes 1, 2
• These dysplastic neutrophils in peripheral blood are among the most reliable features distinguishing MDS from alternative diagnoses 3

Megakaryocytic Dysplasia

• Platelet anisocytosis (variation in platelet size) 1, 2
• Giant platelets 1, 2

Blast Enumeration

• Count and document any circulating blasts—this is critical for accurate MDS classification 1, 2

Technical Requirements for Peripheral Blood Examination

Count at least 200 cells on the peripheral blood smear using May-Grünwald-Giemsa staining for optimal morphologic assessment. 1, 2 Iron staining should also be performed. 2

Critical Limitation: Why Peripheral Blood Alone Is Inadequate

The peripheral blood smear cannot establish an MDS diagnosis by itself because: 2

• Bone marrow examination (aspirate and biopsy) is mandatory to evaluate dysplasia in all three hematopoietic lineages, enumerate blasts accurately, assess ring sideroblasts, and determine cellularity 1, 2
• Cytogenetic analysis is mandatory for both diagnosis and prognostic assessment 1, 2
• >10% of nucleated cells in the affected bone marrow lineage must show dysplastic features to qualify as significant dysplasia 1, 2

When Findings Are Equivocal

If dysplasia is subtle or equivocal on initial evaluation, observe for 6 months with repeat bone marrow investigation before confirming MDS diagnosis. 2, 4 This is particularly important for patients presenting with mild cytopenia only, where rapid disease progression is unlikely. 1

Complete Diagnostic Algorithm Beyond Peripheral Blood

Once peripheral blood raises suspicion for MDS, the following are required:

Mandatory Studies

• Bone marrow aspirate and biopsy (count ≥500 cells including ≥100 erythroblasts and ≥30 megakaryocytes) 1, 2
• Cytogenetic analysis (conventional karyotyping) 1, 2, 4

Recommended Studies

• Flow cytometry immunophenotyping to detect abnormalities in erythroid, myeloid, monocytic, and lymphoid compartments 1, 2
• FISH if standard G-banding cytogenetics repeatedly fails 1, 2

Suggested Studies

• Mutation analysis (particularly TP53 and SF3B1) for prognostic evaluation 2
• SNP array for high-resolution detection of chromosomal defects 1

Common Pitfalls to Avoid

Do not diagnose MDS based on peripheral blood morphology alone, even when dysplastic features are prominent—bone marrow examination and cytogenetics are non-negotiable. 1, 2

Exclude reversible causes of cytopenias including vitamin B12/folate deficiency, drug effects, viral infections, and nutritional deficiencies before pursuing MDS workup. 5, 4

Anemia, dysplastic neutrophils in peripheral blood, and dysplastic megakaryocytes in bone marrow trephine biopsy are the most reliable combined features for distinguishing MDS from other causes of cytopenia. 3