What should the bone marrow in suspected Myelodysplastic Syndromes (MDS) be stained with Prussian blue to check for?

Prussian Blue Stain in Suspected MDS is Used to Check for Ring Sideroblasts

The bone marrow in suspected Myelodysplastic Syndromes (MDS) should be stained with Prussian blue stain to check for ring sideroblasts. 1

Rationale for Prussian Blue Staining in MDS

Prussian blue stain (also called Perls stain) is specifically used in the diagnostic workup of MDS to:

• Detect the presence of ring sideroblasts, which are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation 2
• Evaluate iron stores in the bone marrow
• Help classify MDS subtypes, particularly MDS with ring sideroblasts (MDS-RS)

According to the European Society for Medical Oncology (ESMO) clinical practice guidelines, "Staining for iron with Prussian blue (Perls stain) should always be carried out in lower-risk MDS in order to evaluate the presence of ring sideroblasts." 1

Diagnostic Significance of Ring Sideroblasts

Ring sideroblasts have important diagnostic and classification implications in MDS:

• The presence of ≥15% ring sideroblasts (or ≥5% in the presence of SF3B1 mutations) is a diagnostic criterion for MDS-RS 2
• Ring sideroblasts help differentiate MDS subtypes according to the WHO classification
• The identification of ring sideroblasts has therapeutic implications, as patients with MDS-RS may respond to specific treatments like luspatercept 2

Comprehensive Bone Marrow Evaluation in MDS

When evaluating bone marrow in suspected MDS, multiple stains and assessments are performed:

1. Prussian blue stain: To identify ring sideroblasts and assess iron stores 1
2. Standard morphologic stains: To evaluate dysplasia in erythroid, myeloid, and megakaryocytic lineages 1
3. Cytogenetic analysis: To detect chromosomal abnormalities with diagnostic and prognostic significance 1
4. Bone marrow biopsy: To assess cellularity, fibrosis, and topography 1

Clinical Pearls and Pitfalls

• Important pitfall: Failure to perform Prussian blue staining may result in missing cases with ring sideroblasts, potentially leading to incorrect classification of MDS 3
• Clinical pearl: The presence of ring sideroblasts in combination with thrombocytosis (≥450 × 10^9/L) may indicate MDS/MPN-RS-T (MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis) 2
• Diagnostic caution: Ring sideroblasts alone are not pathognomonic for MDS and can be seen in other conditions such as alcohol abuse, lead poisoning, and certain medications

Answer to Multiple Choice Question

The correct answer is D. Ring sideroblasts.

The other options are incorrect for the following reasons:

• A. Fibrosis - Assessed with reticulin staining, not Prussian blue 1
• B. Type II blasts - Assessed with standard morphologic stains, not Prussian blue
• C. Karyorrhexis - A morphologic feature that lacks specificity for MDS 3 and is not assessed with Prussian blue stain