What are the diagnostic and treatment approaches for a patient with myelodysplastic (MDS) anemia?

Peripheral Smear Findings in Myelodysplastic Syndromes

On a peripheral blood smear in MDS, you will see dysplastic features across one or more cell lines, including erythroid abnormalities (anisocytosis, poikilocytosis, basophilic stippling), myeloid abnormalities (pseudo-Pelger-Huët cells with nuclear hypolobation, hypogranulation/degranulation), megakaryocytic abnormalities (platelet anisocytosis, giant platelets), and potentially circulating blasts. 1

Key Morphologic Features by Cell Line

Erythroid Dysplasia

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

Myeloid Dysplasia

• Pseudo-Pelger-Huët anomaly: granulocytes with nuclear hypolobation (bilobed or monolobed nuclei resembling pince-nez eyeglasses) 1
• Cytoplasmic hypogranulation or complete degranulation of granulocytes 1
• Circulating blasts may be present and must be enumerated 1

Megakaryocytic Dysplasia

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

Diagnostic Approach

Peripheral blood smear examination is mandatory for MDS diagnosis and serves two critical purposes: evaluation of dysplasia in one or more cell lines and enumeration of blasts. 1

Technical Requirements

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

Blast Enumeration Criteria

Myeloblasts are identified by: 1

• High nuclear-to-cytoplasmic ratio
• Easily visible nucleoli
• Fine nuclear chromatin
• Variable cytoplasmic basophilia
• May or may not contain granules or Auer rods
• No Golgi zone detected

Diagnostic Pitfalls and Caveats

The peripheral smear alone is insufficient for MDS diagnosis—it must be combined with bone marrow examination (aspirate and biopsy), cytogenetic analysis, and clinical correlation. 1

When dysplasia is subtle or equivocal: If only unilineage dysplasia is present with normal karyotype, no increase in blasts, and ring sideroblasts <15%, an observation period of 6 months with repeat bone marrow investigation is recommended before confirming MDS diagnosis. 1, 2 These patients typically present with mild cytopenia only, and rapid disease progression is unlikely. 1

Dysplasia threshold: To qualify as significant in bone marrow (which correlates with peripheral findings), >10% of nucleated cells in the affected lineage must show dysplastic features. 1

Complete Diagnostic Workup Beyond Peripheral Smear

While the peripheral smear is mandatory, the complete diagnostic approach requires: 1

• Bone marrow aspirate and biopsy (mandatory)
• Cytogenetic analysis (mandatory for diagnosis and prognostic assessment)
• Flow cytometry immunophenotyping (recommended)
• FISH (recommended if standard cytogenetics fail)
• Mutation analysis (suggested for prognostic evaluation, particularly TP53 and SF3B1) 1