Myelodysplastic syndromes

1. Definition & concept

MDS (previously called “preleukemia”) is a group of clonal stem cell disorders characterized by:

• Failure of maturation of hematopoietic stem cells
• Hypercellular or normocellular BM with dysplasia in one or more lineages
• Cytopenias in the peripheral blood (production is ineffective)
• Genetic instability → risk of acquiring additional mutations → transformation to AML (in 10–40%)

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2. Causes

• Idiopathic (most common)
• After chemotherapy with an alkylating agent
• After ionizing radiation therapy

3. Genetics

Frequent chromosomal alterations:

• Monosomy 5 or 7
• Deletions: del(5q), del(7q), del(20q)

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4. Morphology — dysplasia in all 3 lineages

Dyserythropoiesis

• Nuclear changes: bridging, budding, fragmentation
• Ring sideroblasts: iron-laden mitochondria form a ring around the nucleus

Dysgranulopoiesis

• Pseudo-Pelger anomaly: hyposegmented neutrophils
• Nuclear abnormalities + hypogranulation (few or no granules)

Dysmegakaryopoiesis

• Small megakaryocytes with bridged nuclei
• Large megakaryocytes with isolated nuclear fragments

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5. Classification

1. MDS with single lineage dysplasia — low risk
2. MDS with ring sideroblasts — low risk
3. MDS with isolated del(5q) — low risk; numerous small, mononuclear megakaryocytes
4. MDS with multilineage dysplasia — high risk (all 3 lines affected)
5. MDS with excess blasts (>20%) — high risk

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6. Clinical

• Age: typically 50–70 years old
• Presentation: cytopenias → anemia, granulocytopenia, thrombocytopenia
• Poor response to chemotherapy
• AML transformation: 10–40%
• Median survival: 9–29 months (varies by subtype)

💡 High-yield: MDS = hypercellular BM + peripheral cytopenias (ineffective hematopoiesis). Dysplasia in all 3 lines: ring sideroblasts (RBC), Pseudo-Pelger (neutrophil), micro-megakaryocytes. Key mutations: del(5q), monosomy 7. 10–40% transform to AML.