Abstract
The percentage of blasts cells in the bone marrow (BM) of MDS patients is one of the key parameters for MDS classification and for the differential diagnosis with acute myeloid leukemia (AML). Currently, the gold standard to determine the blast percentage is conventional cytomorphology. To assess the possible impact of blast cell enumeration in BM biopsies from MDS patients on the final WHO classification using CD34 immunohistochemistry (IHC) a total of 156 BM samples from MDS and MDS-AML patients were studied and compared to blast counts by cytomorphology (CM). Eighty-nine BM aspirates were also studied by flow cytometry (FCM). Percentages of CD34+ blasts by IHC were determined blindly by two hematopathologists. Automated CD34-cell count was performed in 25 cases. Good overall agreement was found for CM and FCM with respect to critical blast thresholds (5%, 10%, 20%) (p < 0.05). However, in 17% of patients, CD34+ blast counts by IHC were higher as compared to CM with possible impact on MDS subclassification. In 7 of 21 AML patients, diagnosis was established on BM histology, while the blast percentage by CM was below the AML threshold. The assessment of CD34+ cells by IHC showed high interobserver agreement (Spearman R 0.95, p < 0.01), while automated CD34 counts were not optimal due to interference with other cellular and stromal elements. BM histology including CD34 IHC improves the diagnostic accuracy in MDS and AML. The quantification of blast cells should be based on the integration of all three methods for reliable disease classification and risk assessment.
Highlights
The cytomorphological enumeration of blast percentages in bone marrow (BM) smears is a critical parameter for classification of myelodysplastic syndromes (MDSs) [1]
Enumeration of blast cells in the BM of MDS patients is a key parameter for correct assignment to MDS subgroups, as well as for the differential diagnosis between MDS and acute myeloid leukemia (AML)
Previous studies have shown a generally good correlation between CM and flow cytometry (FCM) for BM blast enumeration [17, 19], but it has been shown that FCM may underestimate or overestimate blast cell counts in individual cases
Summary
The cytomorphological enumeration of blast percentages in bone marrow (BM) smears is a critical parameter for classification of myelodysplastic syndromes (MDSs) [1]. Font et al found low agreement among cytologists when analyzing MDS patients with ≤ 2% BM blast counts [6]. Even when good-quality BM smears are available, the reproducible identification and quantification of blast cells might be a challenge. Blast counts in smears may not be representative due to hemodilution or low cellularity of smears that are often seen in hypoplastic MDS or in MDS with significant (≥ grade 2 WHO) fibrosis [9,10,11,12]. CD34+ cell clusters as identified by immunohistochemistry (IHC) that were reported as independent prognostic marker for progression to AML may be seen even in MDS without blast excess by cytomorphology (CM) [13, 14]. According to European Leukemia Network (ELN) guidelines and the revised WHO classification of MDS, the blast percentage by conventional CM should always be correlated to BM histology including IHC staining for CD34 [15, 16]
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