Bone Marrow Findings in MDS at Different Stages
Bone marrow findings in MDS vary systematically by disease stage, with blast percentage being the most critical prognostic feature, ranging from <5% in lower-risk subtypes to 5-19% in higher-risk RAEB, alongside characteristic dysplastic changes that define each WHO classification subtype. 1
Lower-Risk MDS Subtypes (Blast Count <5%)
Refractory Cytopenia with Unilineage Dysplasia (RCUD)
- Dysplasia: ≥10% of cells in one myeloid lineage only 1
- Blast percentage: <5% in bone marrow 1
- Ring sideroblasts: <15% of erythroid precursors 1
- Specific variants include: Refractory Anemia (RA), Refractory Neutropenia (RN), and Refractory Thrombocytopenia (RT) 1
Refractory Anemia with Ring Sideroblasts (RARS)
- Ring sideroblasts: ≥15% of erythroid precursors (or ≥5% if SF3B1 mutation present) 1
- Dysplasia: Erythroid dysplasia only 1
- Blast percentage: <5% in bone marrow, no blasts in peripheral blood 1
- Prognosis: Low AML progression rate, especially with isolated SF3B1 mutation 1
Refractory Cytopenia with Multilineage Dysplasia (RCMD)
- Dysplasia: ≥10% of cells in two or more myeloid lineages 1
- Blast percentage: <5% in bone marrow 1
- Ring sideroblasts: May be present (±15%) 1
- Auer rods: Absent 1
MDS with Isolated del(5q)
- Megakaryocytes: Normal to increased numbers with hypolobulated nuclei 1
- Blast percentage: <5% in bone marrow 1
- Cytogenetics: Isolated del(5q) chromosomal abnormality is the defining feature 1
- Auer rods: Absent 1
Higher-Risk MDS Subtypes (Increased Blast Count)
Refractory Anemia with Excess Blasts-1 (RAEB-1)
- Blast percentage: 5-9% in bone marrow (or 2-4% in peripheral blood if marrow <5%) 1
- Dysplasia: Unilineage or multilineage dysplasia 1
- Auer rods: Absent 1
- Prognosis: Major risk of progression to AML 1
Refractory Anemia with Excess Blasts-2 (RAEB-2)
- Blast percentage: 10-19% in bone marrow (or 5-19% range) 1
- Dysplasia: Unilineage or multilineage dysplasia 1
- Auer rods: May be present 1
- Critical caveat: Cases with Auer rods and <5% myeloblasts in blood and <10% in marrow should still be classified as RAEB-2 1
- Prognosis: Highest risk of AML transformation and short survival 1
Universal Bone Marrow Features Across All MDS Stages
Cellularity Assessment
- Typical finding: Hypercellular marrow in 63% of cases 2
- Cellularity increases: Progressively higher in RAEB, RAEB-t, and CMML compared to RA/RARS 2
- Hypocellular variants: Require bone marrow biopsy for diagnosis, may mimic aplastic anemia 1
- Prognostic significance: Cellularity independently affects survival (P=0.006) 2
Dysplastic Features by Cell Line
Erythroid dysplasia (present in 72% of cases): 2
- Nuclear abnormalities: multinuclearity, nuclear budding, karyorrhexis 1
- Cytoplasmic changes: megaloblastic features, vacuolization 1
- Ring sideroblasts when present 1
Megakaryocytic dysplasia (present in 83% of cases): 2
- Hypolobulated or non-lobulated nuclei 1
- Micromegakaryocytes 1
- Prognostic impact: Dysmegakaryopoiesis shows borderline relationship with survival (P=0.07) 2
Granulocytic dysplasia: 1
- Nuclear hypolobation (pseudo-Pelger-Huët anomaly) 1
- Cytoplasmic hypogranulation 1
- Abnormal maturation patterns detectable by flow cytometry 3
Topographic Abnormalities
- Abnormal Localization of Immature Precursors (ALIP): Found in >50% of cases, more frequent in RAEB/RAEB-t/CMML 2
- Distribution: Immature precursors located away from normal paratrabecular location 2
Additional Histologic Features
- Reticulin fibrosis: Present in 47% of cases 2
- Eosinophilia: Evident in 26% of cases, correlates with survival (P=0.009) 2
- Plasmacytosis: Present in 18% of cases 2
Critical Diagnostic Requirements
Mandatory Bone Marrow Evaluation
- Aspirate: Evaluation of dysplasia, blast enumeration (count 500 cells), ring sideroblast enumeration 1
- Biopsy: Assessment of cellularity, fibrosis, topography, and ALIP 1
- Both procedures strongly recommended: Biopsy provides independent prognostic information beyond aspirate morphology 1, 2
Blast Counting Pitfalls
- Paramount prognostic value: Bone marrow blast count is the most critical parameter 1
- Discordance handling: If marrow blasts <5% but peripheral blood shows 2-4% blasts, classify as RAEB-1 1
- Auer rod exception: Presence of Auer rods with <5% blood blasts and <10% marrow blasts mandates RAEB-2 classification 1
Cytogenetic Integration
- Clonal abnormalities: Observed in >80% of MDS patients 1
- Highest prognostic weight: Karyotype has the strongest impact in IPSS-R scoring 1
- Diagnostic utility: Specific abnormalities (del(5q), -7/del(7q), complex karyotype) can establish MDS diagnosis even with minimal dysplasia 1
Staging Implications
Lower-risk MDS (IPSS Low/Intermediate-1): 1
- Bone marrow blasts <5% 1
- Predominantly single or multilineage dysplasia without excess blasts 1
- Longer survival, death often from non-MDS causes 1
Higher-risk MDS (IPSS Intermediate-2/High): 1