title: Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes.
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.
authors.affiliation: 1] Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Internal Medicine, University of Pavia, Pavia, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Della Porta
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Travaglino
authors.affiliation: Anatomic Pathology Section, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Boveri
authors.affiliation: Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: 1] Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Malcovati
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: E
authors.initials: E
authors.lastname: Papaemmanuil
authors.affiliation: Hematology Section, Department of Medical Sciences, University of Ferrara, University Hospital Arcispedale S. Anna, Ferrara, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Rigolin
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pascutto
authors.affiliation: 1] Anatomic Pathology Section, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Croci
authors.affiliation: Hematopathology Service, Pathology Unit, Department of Pathophysiology and Transplantation, University of Milano Medical School, Milano, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Gianelli
authors.affiliation: Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Milani
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Ambaglio
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Elena
authors.affiliation: 1] Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ubezio
authors.affiliation: 1] Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Da Via'
authors.affiliation: 1] Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bono
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pietra
authors.affiliation: Department of Internal Medicine, University of Pavia, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Quaglia
authors.affiliation: Department of Internal Medicine, University of Pavia, Pavia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bastia
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ferretti
authors.affiliation: Hematology Section, Department of Medical Sciences, University of Ferrara, University Hospital Arcispedale S. Anna, Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.affiliation: Department of Hematology Oncology, Niguarda Ca' Granda Hospital, Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Morra
authors.affiliation: 1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK [2] Department of Haematology, University of Cambridge, Cambridge, UK [3] Department of Haematology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Campbell
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Orazi
authors.affiliation: Department of Internal Medicine, University of Pavia, Pavia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Invernizzi
authors.affiliation: 1] Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification* / Q000473:pathology; D012720:Severity of Illness Index; D014944:World Health Organization