European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis

Abstract

BackgroundThe World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. Design and MethodsTo assess the reproducibility of the classification, six hematopathologists from five European countries re-classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. ResultsConsensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. ConclusionsWorld Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone.

European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. Haematologica 2012;97(3):360-5 - Comment

“…7 The high concordance in that study, in contrast with what is claimed in the paper by Buhr et al, 1 was obtained in the absence of any prior consensus conference or training. On the other hand, after such a consensus meeting between pathologists and clinicians, the concordance in the final clinical diagnosis was 82% for the total cohort and 93% for the prevalent group of ET versus early PMF patients (kappa=0.740; P=0.001), i.e.…”

Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms

“…The four reviewers were instructed to classify the quantitative morphological variables (numbered 1, 2, 4, 6, 7) with three possible categories ('reduced', 'normal' or 'increased') and the qualitative variables (numbered 3,5,[8][9][10][11][12][13][14][15][16][17][18] with two ('absent' or 'present'). 12 To register a qualitative variable as 'present', the reviewer had to identify that specific morphological features at least two times in the same slide.…”

“…Most of the diagnosis of myeloproliferative neoplasms 'unclassifiable' derive by the impossibility to reach a conclusive diagnosis in the presence of clinical or morphological features that, according to the WHO classification, are borderline with different myeloproliferative neoplasms. Recently, the reproducibility of histopathology of bone marrow according to WHO classification and its usefulness for identifying different myeloproliferative neoplasms has been questioned, [8][9][10] and subsequent controversies between supporters and opponents have been raised in this setting.…”

Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia

“…7 Particular in the early stages, both the clinical presentation and the histopathological appearance of ET and PMF can be similar, a problem that has sparked lively discussion on distinguishing diagnostic criteria, including those of the WHO classification. [8][9][10] In addition, the WHO classification has been criticized for relying on histopathology, which may be subject to a high degree of interobserver variability. 8,9 However, because of the large difference in clinical course and outcome between ET and PMF, accurate classification and diagnosis of these entities is essential.…”