What are the expected bone marrow findings in a patient with suspected Myelodysplastic Syndrome (MDS) presenting with pancytopenia and macrocytic anemia?

Expected Bone Marrow Findings in Myelodysplastic Syndrome (MDS)

In a patient with suspected MDS presenting with pancytopenia and macrocytic anemia, expect bone marrow hypercellularity (in most cases) with dysplastic changes affecting ≥10% of cells in one or more myeloid lineages, variable blast percentage (<20%), and cytogenetic abnormalities in 50-60% of cases. 1

Cellularity Patterns

• Most MDS cases demonstrate hypercellular or normocellular bone marrow despite peripheral cytopenias, reflecting ineffective hematopoiesis 1
• Hypocellular MDS occurs in a minority (approximately 10-15% of cases), characterized by marrow cellularity ≤25%, more severe cytopenias (median platelets 28,000/μL vs 75,000/μL), and marked macrocytosis (MCV 107 fL vs 97 fL) 2
• Hypocellular MDS typically shows normal cytogenetics (100% vs 77% in hypercellular MDS) and may be difficult to distinguish from aplastic anemia 2

Morphologic Dysplasia Requirements

The diagnostic threshold requires dysplasia in ≥10% of nucleated cells within the affected lineage(s). 1 Proper assessment mandates:

• Counting ≥500 cells in bone marrow smears, including at least 100 erythroblasts and 30 megakaryocytes 1
• May-Grünwald-Giemsa and iron staining for comprehensive evaluation 1

Erythroid Dysplasia Features

• Nuclear abnormalities: Binuclearity, internuclear bridging, irregular nuclear edges, megaloblastoid changes 1
• Cytoplasmic findings: Ring sideroblasts (≥15% defines RARS subtype), cytoplasmic inclusions 1
• Erythroid hyperplasia may be prominent, with nucleated red cells comprising >50% of marrow cellularity in some cases 3

Myeloid Dysplasia Features

• Nuclear abnormalities: Hypolobation (pseudo-Pelger-Huët), hypersegmentation, bizarre nuclear shapes 1
• Cytoplasmic findings: Hypogranulation/degranulation 1
• Flow cytometry shows decreased CD10+ granulocytes, increased CD56+ granulocytes, and elevated immature-to-mature cell ratios 4

Megakaryocytic Dysplasia Features

• Characteristic findings: Large monolobular forms, small binucleated elements, micromegakaryocytes, hypolobated nuclei 1
• Megakaryocytic dysplasia is often better evaluated on bone marrow sections than smears 1

Blast Percentage

Blast enumeration is critical for accurate MDS classification and prognostication. 1

• <5% blasts: Refractory cytopenia with unilineage dysplasia (RCUD), RARS, or refractory cytopenia with multilineage dysplasia (RCMD) 1
• 5-9% blasts: RAEB-1 1
• 10-19% blasts: RAEB-2 1
• Myeloblast definition: High nuclear/cytoplasmic ratio, visible nucleoli, fine nuclear chromatin, variable cytoplasmic basophilia, with or without granules/Auer rods but no Golgi zone 1

Cytogenetic Abnormalities

Cytogenetic analysis should be performed in all suspected MDS cases, analyzing ≥20 metaphases when possible. 1

Most Common Abnormalities

• del(5q): 10-15% of cases 1
• Monosomy 7 or del(7q): 10% 1
• Trisomy 8: Common, though not listed as presumptive evidence alone 1
• del(20q): Frequent but not diagnostic alone 1

Diagnostic Significance

• Chromosomal abnormalities occur in 50-60% of MDS patients 1
• Specific recurrent abnormalities (del(5q), monosomy 7/del(7q), i(17q)/t(17p), del(11q), del(12p), del(13q), del(9q), and specific balanced translocations) provide presumptive evidence of MDS even with <10% dysplasia 1
• Normal karyotype is more common in hypoplastic MDS (100% vs 77%) 2

Flow Cytometry Findings

Flow cytometry abnormalities involving one or more myeloid lineages are suggestive but not diagnostic of MDS alone. 1

• Erythroid abnormalities: Higher proportions of immature cells, decreased CD71 expression on nucleated red cells 4
• Myeloid abnormalities: Lower CD10+ granulocytes, higher CD56+ granulocytes, increased immature-to-mature cell ratios 4
• ≥3 phenotypic abnormalities involving myeloid lineages can be considered indicative of MDS when combined with other findings 1

Special Patterns and Pitfalls

Abnormally Localized Immature Precursors (ALIP)

• ALIP presence indicates worse prognosis with increased propensity for leukemic transformation 5
• Must distinguish true myeloid/monocytic ALIP from benign erythroid or megakaryocytic aggregates using immunohistochemistry 5

Common Diagnostic Challenges

• Hypoplastic MDS vs. aplastic anemia: Hypoplastic MDS shows dysplasia ≥10%, may have cytogenetic abnormalities, and lacks response to immunosuppressive therapy 2
• MDS-U classification: Used for cases with pancytopenia and unilineage dysplasia, or <10% dysplasia with diagnostic cytogenetic abnormalities 1
• If unilineage dysplasia only without diagnostic cytogenetics, blasts <5%, and ring sideroblasts <15%, observe for 6 months with repeat bone marrow before confirming MDS diagnosis 1

Bone Marrow Architecture

• Immunohistochemistry on bone marrow biopsies helps identify dysplastic features (mononuclear megakaryocytes, Pelger-Huët neutrophils, binuclear erythroblasts) and assess microarchitecture alterations 5
• Reticulin staining should be performed to assess for fibrosis 5