Macrocytosis With Mild Cytopenias: Marrow Now or Later?
A 72-year-old woman has Hb 10.2 g/dL, MCV 104 fL, WBC 3.4 ×10^9/L, and platelets 130 ×10^9/L. She has no alcohol use, no B12 or folate deficiency, normal TSH, and no new medications. The smear shows oval macrocytes and rare five-lobed neutrophils but no clear hypogranularity. Reticulocyte count is 1.2%. She feels well. The primary care physician asks whether to refer for bone marrow biopsy now or repeat the CBC in 6 months.
1. What is your next step, and why is marrow not automatically indicated?
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First repeat the CBC in 4 to 6 weeks and look for a trend, because isolated macrocytosis with mild cytopenias is often reactive. Check copper, renal and liver function, reticulocyte count, LDH, haptoglobin, and a medication and alcohol history. Review the smear for oval macrocytes, hypersegmented neutrophils, and dysplasia. Bone marrow is reasonable if cytopenias persist or progress, if dysplasia is seen on smear, or if there is unexplained blasts or cytogenetic concern. A single mild abnormal CBC does not mandate immediate biopsy.
2. If marrow shows 5% blasts and multilineage dysplasia, what is the diagnosis and what prognostic workup is needed?
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This is a myelodysplastic syndrome with increased blasts, specifically MDS with 5–9% marrow blasts and fewer than 5% blood blasts, consistent with MDS-EB-1 in older terminology. Order karyotype and FISH, and send targeted myeloid next-generation sequencing, including TP53, SF3B1, TET2, ASXL1, and RUNX1. Assess ring sideroblasts with iron stain and evaluate the IPSS-R or molecular prognostic score. These results guide monitoring and treatment intensity.
3. How do you avoid overdiagnosing dysplasia in a reactive marrow?
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Require dysplasia in at least 10% of cells in one or more lineages and correlate with cytopenias and clinical context. Exclude B12 or folate deficiency, copper deficiency, HIV, parvovirus, alcohol, medication effects, and toxic exposures. Reactive changes can mimic dysplasia, especially in neutrophils and erythroid precursors. Use iron stain, flow cytometry, cytogenetics, and repeat marrow if needed. Do not diagnose MDS from a single smear or a minor dysplastic subset without supporting clinical and laboratory evidence.