Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

Senent, Leonor; Arenillas, Leonor; Luño, Elisa; Ruiz, Juan Carlos; Sanz, Guillermo; Florensa, Lourdes

doi:10.3324/haematol.2012.071449

Cited by 67 publications

(51 citation statements)

References 32 publications

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“…Although the threshold to define dysplasia will remain as 10% dysplastic cells in any hematopoietic lineage, it is recognized that dysplasia in excess of 10% may occur in some normal individuals and even more frequently in nonneoplastic causes of cytopenia. 50,51 Moreover, identification of dysplasia is not always reproducible among even experienced hematopathologists. 52,53 For these reasons, possible reactive etiologies of dysplasia should always be carefully considered prior to making a diagnosis of MDS, particularly when the dysplasia is subtle and limited to 1 lineage.…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

8,263

7,810

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The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

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Section: Myelodysplastic Syndromesmentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

8,263

7,810

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“…1,2 The presence of dysplasia in one or more of myeloid cell lines is one of the major criteria for the diagnosis of MDS; however, dysplasia is not specific, and its morphologic criteria are poorly reproducible. 3,4 In a group of myeloid disorders classified on the basis of morphologic criteria, identifying specific associations between genotype and disease phenotypes is essential to defining disease entities according to their distinctive genetic profiles. 5 This genotype-phenotype relationship in MDS is illustrated by the 5q-syndrome, described as a distinct clinical entity by Van den Berghe et al in 1974.…”

Section: Introductionmentioning

confidence: 99%

Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia

Malcovati

Papaemmanuil

Ambaglio³

et al. 2014

Blood

229

159

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Key Points• Different driver mutations have distinct effects on phenotype of myelodysplastic syndromes (MDS) and myelodysplastic/ myeloproliferative neoplasms (MDS/MPN).• Accounting for driver mutations may allow a classification of these disorders that is considerably relevant for clinical decision-making. Irrespective of driver somatic mutations, a threshold of 5% bone marrow blasts retained a significant discriminant value for identifying cases with clonal evolution. Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. These results serve as a proof of concept that a molecular classification of myeloid neoplasms is feasible. (Blood. 2014;124(9):1513-1521

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“…We read with great interest the recent paper by Senent et al 1 and the accompanying editorial 2 on the reproducibility of WHO 2008 criteria and inter-observer agreement regarding the assessment of dysplasia for diagnosis and classification of myelodysplastic syndromes (MDS). The reproducibility of any composite criteria is mainly based on both the constituting components and the precise manner in which they are actually handled.…”

Section: Inter-observer Agreement In Myelodysplastic Syndromesmentioning

confidence: 99%

Inter-observer agreement in myelodysplastic syndromes

Ramos

Fernández-Ferrero

2013

Haematologica

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We read with great interest the recent paper by Senent et al. 1 and the accompanying editorial 2 on the reproducibility of WHO 2008 criteria and inter-observer agreement regarding the assessment of dysplasia for diagnosis and classification of myelodysplastic syndromes (MDS). The reproducibility of any composite criteria is mainly based on both the constituting components and the precise manner in which they are actually handled. The WHO 2008 classification is based on the quantification of bone marrow (BM) and peripheral blood blasts, degree of dyshemopoietic findings, precise peripheral blood cytopenias actually observed, presence or absence of Auer rods, as well as some cytogenetic features (i.e. the presence of 5q abnormalities), the way they must be handled being set out in the original WHO document.The results from Senent and co-workers' study of 50 MDS cases are based on a "blind and independent microscopical review by four cytologists from three centers". 1Their paper has a very high methodological quality and confirms our group's 1999 findings 3 based on 26 MDS cases and 24 control patients collected in one single center and performed by "five independent observers in a blinded manner"; 3 only one of them was actually a cytologist, the others being either clinical hematologists or hematologists in training. Obviously, the number of observers, their cytological expertise, as well as the number of participating centers may have a role in the degree of inter-observer agreement but, interestingly enough, their results on individual cytological features do not seem to differ from our earlier work, and cast doubt on whether the observer's expertise or, conversely, the subjectivity of the pathological findings concerned are the main contributors to the observed heterogeneity. As stressed in John Bennnett's editorial, 2 two main cytological features, namely BM blast cells and the proportion of pathological sideroblasts, are the most reproducible data in MDS patients, whereas the degree of dyserythropoietic findings, excluding sideroblasts, is the least reproducible. In addition, Senent and coworkers also showed that the concordance of the cut-off point for granulocytic (and megakaryocytic) lineage expressed by the kappa statistic is much higher for the 40% figure than for the WHO-based 10% value (kappa 0.40 vs. 0.19). Again, this agrees with our previous findings that showed that the percentage of dysgranulopoietic findings in control patients might be much higher than 10% (p90: 27%); something that suggests that the WHO 10% cut-off was not a good choice.Finally, despite the quality of the data presented in Senent´s paper, some questions remain to be addressed in the future: the inter-observer agreement of BM blasts was uncomfortably low when the observed proportion was located between 2% and 10%, a fact that may explain the discordance between their paper and other recently published work 4 based on 100 MDS cases "collected from 10 hospitals and…evaluated by 10 morphologists, working in five pairs": inter-o...

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Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

Cited by 67 publications

References 32 publications

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia

Inter-observer agreement in myelodysplastic syndromes

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