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Myelodysplasias

Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes

Leukemia volume 29, pages 66–75 (2015)Cite this article

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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.

Author information

Author notes

  1. M G Della Porta, E Travaglino and E Boveri: These author contributed equally to this work.

  2. R Invernizzi and M Cazzola: RI and MC are equal senior authors.

Authors and Affiliations

  1. Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    M G Della Porta, E Travaglino, L Malcovati, C Pascutto, I Ambaglio, C Elena, M Ubezio, M C Da Via’, E Bono, D Pietra, V Ferretti & M Cazzola

  2. Department of Internal Medicine, University of Pavia, Pavia, Italy

    M G Della Porta, F Quaglia, R Bastia & R Invernizzi

  3. Anatomic Pathology Section, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    E Boveri & G Croci

  4. Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy

    M Ponzoni & R Milani

  5. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    L Malcovati, G Croci, M Ubezio, M C Da Via’, E Bono & M Cazzola

  6. Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK

    E Papaemmanuil & P J Campbell

  7. Department of Medical Sciences, Hematology Section, University of Ferrara, University Hospital Arcispedale S. Anna, Ferrara, Italy

    G M Rigolin & A Cuneo

  8. Department of Pathophysiology and Transplantation, Hematopathology Service, Pathology Unit, University of Milano Medical School, Milano, Italy

    U Gianelli

  9. Department of Hematology Oncology, Niguarda Ca' Granda Hospital, Milano, Italy

    E Morra

  10. Department of Haematology, University of Cambridge, Cambridge, UK

    P J Campbell

  11. Department of Haematology, Addenbrooke’s Hospital, Cambridge, UK

    P J Campbell

  12. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

    A Orazi

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  1. M G Della Porta
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on behalf of Rete Ematologica Lombarda (REL) clinical network

Corresponding authors

Correspondence to M G Della Porta or M Cazzola.

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The authors declare no conflict of interest.

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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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