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

Abstract

This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n ¼ 34), primary myelofibrosis (n ¼ 44) and polycythaemia vera (n ¼ 25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement (Z70%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic 40.40). In conclusion, our results support the use of the histological criteria proposed by the WHO

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

“…Standardized morphologic criteria of MPNs are important to enhance interobserver reproducibility of morphologic diagnoses (which currently demonstrates consensus rates ranging between 76% and 88%, depending on the study design). 12,13,[16][17][18] The revised criteria for CNL, PV, ET, PMF, and prePMF are listed in Tables 3-7 in addition to a slightly modified grading of reticulin and collagen BM fibers (Table 8). It is important to emphasize that an accurate histologic diagnosis has been proven to be key to predict prognosis in this group of diseases.…”

Cooperation between pathologists and clinicians allows a better diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms

“…There were high levels of agreement (70%) in relation to almost all of the morphological features and a high percentage of crude agreement concerning the diagnoses (76%), albeit with only moderate to good values of Cohen's kappa statistic (ranging from 0.41 to 0.80). Morphology alone was sufficient to classify 72% of the cases correctly [76]. These findings allow us to suggest that further improvements can be made in order to ensure a more precise early diagnosis of patients affected by these dramatic diseases, by means of the organization of larger consensus conferences.…”

Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis

“…[4][5][6][7] A low interobserver concordance in applying the WHO-based histopathology criteria for pre-PMF was questioned by some experts, [6][7][8] whereas others clearly delineated the reproducibility of those criteria and the clinical relevance of adopting the diagnostic concept of pre-PMF. [9][10][11] In the largest multicenter study, which included 1104 patients with a diagnosis of ET who underwent revision of their diagnostic biopsies (resulting in 16% of them to be reclassified as pre-PMF), significant differences were found in the occurrence of bleeding, 12 rate of death, progression to overt myelofibrosis, and transformation to leukemia, signifying the relevance of differentiating pre-PMF from ET. 12 In this study, we aimed at assessing, in a real-life setting, the importance of distinguishing pre-PMF and overt PMF, as delineated by modern WHO criteria, concerning the clinical and hematologic presentation, the molecular profile, and the outcome.…”