A systematic classification of megakaryocytic dysplasia and its impact on prognosis for patients with myelodysplastic syndromes

Background: Dys-megakaryopoiesis is defined as ≥10 % of dysplastic megakaryocytes in bone marrow smears by the World Health Organization. However, concordance rates for dysplastic megakaryocytes between different observers is low and, consequently, evaluation of dysmegakaryopoiesis is also often discordant. Results: We performed CD41 immune staining and proposed a systematic classification of dys-megakaryopoiesis on bone marrow films: (1) micro-megakaryocytes (<12 μm); (2) micro-megakaryocytes (12-40 μm) with 1 nucleus; (3) micro-megakaryocytes (12-40 μm) with 2 nuclei; (4) micro-megakaryocytes (12-40 um) with multiple (more than 2) nuclei; (5) dysplastic megakaryocytes (≥40 μm) with 1 nucleus; (6) dysplastic megakaryocytes (≥40 μm) with 2 nuclei; and (7) dysplastic megakaryocytes (≥40 μm) with multiple (more than 2) nuclei. Further, we evaluated the prognostic impact of micro-megakaryocytes and dysplastic mono-nucleated megakaryocytes on MDS patients. The best discriminator cut-off point for each group was determined by the minimal P value approach. In multivariate analyses micro-megakaryocytes ≥25 % and dysplastic mono-nucleated megakaryocytes ≥30 % were independent adverse prognostic factors (hazard ratio [HR] = 1.58 [95 % confidence interval [CI], 1.11, 2.23]; P = 0.010 and 1.53 [1.09, 2.16]; P = 0.014). Conclusions: Our data suggest integration of micro-megakaryocytes and dysplastic mono-nucleated megakaryocytes improve predictive accuracy of the international prognostic scoring system-revised (IPSS-R) scoring system.