CD34+ Myeloblasts: Disease Associations
CD34+ myeloblasts are characteristically seen in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), where CD34 serves as a critical immunohistochemical marker for identifying and quantifying blast cells in bone marrow specimens. 1
Primary Disease Associations
Acute Myeloid Leukemia (AML)
- CD34 expression occurs in a subset of AML patients, with the CD34+CD38- population representing the leukemic stem cell compartment that survives chemotherapy and drives minimal residual disease 2
- The percentage of CD34+ blasts varies widely among AML patients, with some showing >80% CD34+ cells while others are considered CD34-negative by conventional criteria 3
- CD34 expression >7% on blasts predicts poor prognosis in NPM1-mutated AML, independent of FLT3-ITD status, with lower complete remission rates and worse overall survival 4
- In AML, the ratio of CD34+ cells to bone marrow blasts is approximately 0.23, significantly lower than in MDS 5
Myelodysplastic Syndromes (MDS)
- CD34 immunohistochemistry is particularly valuable for identifying blasts in hypocellular or fibrotic MDS bone marrow specimens where morphologic assessment alone may be inadequate 1
- Most cases of MDS with myelofibrosis demonstrate excess blasts readily appreciated by CD34 immunohistochemical staining on biopsy 1
- The ratio of CD34+ cells to bone marrow blasts in MDS is approximately 1:1 overall, but increases to 1.6 in refractory anemia (RA) and ring sideroblastic anemia (RAS) 5
- Aggressive MDS subtypes show abnormal blast aggregates or clusters (ALIP - abnormally localized immature myeloid precursor cells) that are CD34-positive, associated with poor prognosis and increased progression to acute leukemia 1
Diagnostic Utility of CD34 Staining
Technical Considerations
- CD34 is expressed on progenitor and early precursor marrow cells, making it one of the most useful markers for counting blasts in tissue sections 1
- Flow cytometry and immunohistochemistry show good correlation for CD34 quantification in both MDS (p<0.0001) and AML (p<0.01), though flow cytometry may yield higher percentages in cases with numerous CD34+ cells 5
- In markedly hypocellular bone marrow aspirates with low CBC counts and absence of increased blasts, the value of CD34 immunohistochemistry has not been proven 1
Differential Diagnosis Algorithm
- Quantify CD34+ blasts using immunohistochemistry on bone marrow biopsy, particularly when aspirates are hypocellular or fibrotic 1, 6
- Correlate CD34 staining with morphology and cytogenetics to distinguish between hypocellular AML, hypocellular MDS, and aplastic anemia 1, 7
- Look for abnormal blast clustering (ALIP) in central marrow cavity locations rather than normal paratrabecular distribution—presence of ≥3 aggregates (>5 myeloid precursors) or clusters (3-5 precursors) indicates aggressive MDS 1
- Perform 500-cell differential count to ensure reliable blast percentage determination, as 100-cell counts have wide confidence intervals 1, 6
Critical Distinctions
MDS vs. Aplastic Anemia
- Blast percentage <1% in aplastic anemia vs. ≥5% in MDS (or 2-4% in peripheral blood with other MDS features for RAEB-1) 1, 7
- Presence of easily identifiable megakaryocytes within architecturally disorganized marrow and reticulin fibrosis favor MDS over aplastic anemia 1
- Age-corrected bone marrow cellularity is essential—failure to correct for age leads to overdiagnosis of hypocellular conditions 1, 7
Common Pitfalls
- Flow cytometry results should never replace morphological inspection of peripheral blood film, bone marrow aspirate smears, and bone marrow biopsy, as hemodilution in fatty or fibrotic marrows can affect blast percentages 1
- Other immature cells (proerythroblasts, lymphoid subsets) may be mistaken for blasts by morphology alone—CD34 staining helps avoid this error 1
- Not all blasts express CD34—supplementary markers including CD117, myeloperoxidase, lysozyme, and CD68 may be necessary 1, 6