Abstract
The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.
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Acknowledgements
This study was supported by the Fondazione Berlucchi, Brescia, Fondazione Veronesi, Milan, Fondazione IRCCS Policlinico San Matteo, Pavia, and Fondazione Cariplo/Regione Lombardia, Milan, Italy, to MGDP and by the Associazione Italiana per la Ricerca sul Cancro, Milan, and Fondazione Cariplo, Milan, to MC.
Author contributions
MGDP, ET, EB, RI and MC conceived this study. ET, EB, MP, LM, GMR, UG, RM, IA, CE, MU, GC, FQ, RB, AC, EM and AO collected data. EP, DP and PJC performed molecular analyses. CP and VF analyzed the data. MGDP, ET, EB, MP, AO, RI and MC wrote the manuscript, which was approved by all authors.
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Della Porta, M., Travaglino, E., Boveri, E. et al. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia 29, 66–75 (2015). https://doi.org/10.1038/leu.2014.161
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DOI: https://doi.org/10.1038/leu.2014.161
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