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The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and determining individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts). Therefore, there is clearly a need to refine the accuracy to detect marrow dysplasia. Flow cytometry (FCM) immunophenotyping has been proposed as a tool to improve the evaluation of marrow dysplasia. Rationale for the application of FCM in the diagnostic work up of MDS is that immunophenotyping is an accurate method for quantitative and qualitative evaluation of hematopoietic cells and that MDS have been found to have abnormal expression of several cellular antigens. To become clinically applicable, FCM analysis should be based on parameters with sufficient specificity and sensitivity, data should be reproducible between different operators and the results should be easily understood by clinicians. In this report, we reviewed the most relevant progresses in detection of marrow dysplasia by FCM in MDS as defined by WHO criteria.

Bone marrows from 23 patients with haemopoietic dysplasia were cultured in agar-gel and the patients were followed for at least 6 months after culture. The incidence of colonies, microclusters and macroclusters and the colony to cluster and microcluster to macrocluster ratios were compared to those of a control group. In the control patients a normal wide range of colonies and clusters was observed and colony growth correlated with cluster growth. About half of the dysplastic patients showed a normal growth pattern and ran a stable and benign course. The other dysplastic patients had defective colony growth, a low colony to cluster ratio, an increased microcluster to macrocluster ratio and a deficient macrocluster growth early in culture. These patients more often presented with cytopenia and had a malignant course with increasing bone marrow dysplasia and a frequent need of blood transfusions. Some patients died of cytopenia or transformed into acute leukaemia. The bone marrow cultures of haemopoietic dysplasia did not predict the short term (within 6 months) risk of leukaemia transformation. However, the results indicate that examination of culture growth can be used to differentiate stable and benign patients from those in whom clonal abnormalities may suggest a progressive and malignant course.

Dysplastic features of cells in peripheral blood and bone marrow were studied in 51 patients with myelodysplastic syndromes (MDS) to evaluate the significance of the degree of neutrophil granulation (G-score) and the percentage of pelgeroid polymorphs (ppp) in the peripheral blood, as indices of dysplastic changes in the bone marrow. There was a good correlation between peripheral blood and bone marrow findings, both for G-score figures (r = 0.92, P0.01) and ppp (r = 0.82, P0.01). Significantly lower G-score figures were found among patients with an increased percentage of bone marrow blasts (P0.05), while high ppp correlated with the presence of ring sideroblasts, the degree of bone marrow fibrosis, and findings of complex chromosomal abnormalities. Patients with a high degree of bone marrow dysplasia had significantly lower G-score (P0.01) and significantly higher ppp (P0.05) figures, than those with less pronounced myelodysplasia. In addition, extreme hypogranulation (G-score150) or very high ppp (or = 20%) was generally a sign of bi- and tri-lineage dysplasia in the bone marrow. The results thus show that quantitative estimation of peripheral blood polymorph dysplasia by G-score figures and ppp seems to reflect the total degree of bone marrow dysplasia in MDS and may serve as a complement to bone marrow evaluation when the diagnosis of MDS is difficult.