What is the diagnosis and management for a patient with normocellular bone marrow, trilineage hematopoiesis, ring sideroblasts, macrocytic anemia, mild leukopenia, and thrombocytopenia?

Interpretation of Bone Marrow Findings: Myelodysplastic Syndrome with Ring Sideroblasts

The bone marrow findings are most consistent with Myelodysplastic Syndrome (MDS), specifically a lower-risk MDS with ring sideroblasts. The presence of normocellular marrow with trilineage hematopoiesis, occasional ring sideroblasts, and peripheral blood cytopenias (macrocytic anemia, mild leukopenia, thrombocytopenia) without increased blasts supports this diagnosis 1.

Diagnostic Assessment

Key Findings Supporting MDS Diagnosis:

• Normocellular bone marrow (40-60%)
• Trilineage hematopoiesis with dysplastic features
• Occasional ring sideroblasts
• Peripheral blood abnormalities:
  • Macrocytic anemia
  • Mild leukopenia
  • Thrombocytopenia
• No increase in blasts (favorable prognostic feature)
• Polytypic plasma cells (5-6%, not indicative of plasma cell disorder)

Diagnostic Criteria Met:

According to WHO criteria, this case meets diagnostic requirements for MDS 1:

1. Persistent cytopenias (affecting multiple lineages)
2. Morphologic dysplasia (implied by the presence of ring sideroblasts)
3. Absence of other causes that could explain the findings

Classification and Prognostic Assessment

Based on the findings, this likely represents a lower-risk MDS with ring sideroblasts. The exact WHO classification would depend on:

• Percentage of ring sideroblasts (described as "occasional" - likely <15%)
• Extent of dysplasia in each lineage
• Absence of increased blasts

For accurate prognostic assessment, the Revised International Prognostic Scoring System (IPSS-R) should be applied, which considers:

• Cytogenetic abnormalities (not provided in this case)
• Blast percentage (<5% in this case)
• Hemoglobin level, platelet count, and neutrophil count 1

Management Approach

Initial Workup:

1. Complete cytogenetic analysis to identify any chromosomal abnormalities 1
2. Molecular testing for common MDS-associated mutations (particularly SF3B1, which is associated with ring sideroblasts) 1
3. Exclusion of other causes of cytopenias and ring sideroblasts:
   • Vitamin B12 and folate levels (especially with macrocytic anemia)
   • Iron studies (ferritin, transferrin saturation)
   • Copper deficiency
   • Medication/toxin exposure
   • Alcohol intake assessment 1, 2

Treatment Strategy:

For lower-risk MDS with cytopenias:

1. Anemia management:

   • Erythropoiesis-stimulating agents (ESAs) with or without G-CSF based on serum erythropoietin level 1
   • If SF3B1 mutation is present, consider luspatercept (particularly effective in MDS with ring sideroblasts) 1
   • Red blood cell transfusions for symptomatic anemia if unresponsive to other therapies

2. Thrombocytopenia management:

   • Platelet transfusions for severe thrombocytopenia or bleeding
   • Consider thrombopoietin receptor agonists if platelet count is severely low 1

3. Neutropenia management:

   • Infection prophylaxis and prompt treatment of infections
   • Short-term G-CSF for severe neutropenia with infection 1

4. Disease-modifying therapy:

   • For higher-risk features or disease progression: hypomethylating agents (azacitidine) 3
   • For eligible patients with poor prognostic features: consideration of allogeneic stem cell transplantation

Monitoring and Follow-up

1. Regular blood count monitoring (every 1-3 months depending on severity)
2. Repeat bone marrow examination if:
   • Significant change in blood counts
   • New cytogenetic abnormalities suspected
   • Disease progression suspected
3. Monitor for transformation to higher-risk MDS or acute myeloid leukemia

Important Considerations

• The presence of occasional ring sideroblasts is significant but not diagnostic of a specific MDS subtype unless they constitute ≥15% of erythroid precursors 1
• The combination of ring sideroblasts with thrombocytosis should raise suspicion for MDS/MPN overlap syndrome, specifically MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), though this patient has thrombocytopenia rather than thrombocytosis 4, 5
• If the diagnosis remains uncertain due to minimal dysplasia or non-specific findings, a 6-month observation period with repeat bone marrow examination is recommended 1

The prognosis for lower-risk MDS is generally better than higher-risk disease, with median survival often measured in years rather than months, particularly with appropriate supportive care and targeted interventions.