Evolution of WHO diagnostic criteria in “Classical Myeloproliferative Neoplasms” compared with the International Consensus Classification

Abstract

A lively discussion persists regarding the diagnostic criteria for essential thrombocythemia (ET), primary myelofibrosis (PMF) and polycythemia vera (PV), particularly in relation to early/pre-fibrotic myelofibrosis (pre-PMF), a disease entity initially introduced in 2001 by the 3^rd edition of the World Health Organization (WHO) classification. The definition and criteria used to diagnose pre-PMF have been progressively modified over time. The most update definition of pre-PMF can be found in the International Consensus Classification (ICC) published in 2022. An updated largely similar definition is also incorporated in the recently published 5^th edition of WHO classification (2024). Diagnostic criteria for ET have undergone changes up to 2016/17 for the revised 4^th edition of the WHO. In particular the threshold value for platelets were lowered and the important discrimination between “true” and “false” ET (in reality pre-PMF) been widely acknowledged. To avoid misdiagnose in early phase PV, the criteria for gender-adjusted thresholds for hemoglobin/ hematocrit have been lowered and the identification of an appropriate bone marrow (BM) morphology was upgraded as a major diagnostic criterion. Given the prominent role of morphology in MPN-related diagnostic algorithms, the diagnostic adequacy of the BM biopsy (sample procurement and proper laboratory handling) as emphasized in former WHO editions and in the ICC, was not addressed by the WHO 5^th. The essential role of genetic markers is recognized by both classifications. A comparison between the revised 4^th edition WHO classification and the ICC versus the WHO 5^th reveals no significant differences, with the exception of the occurrence of leukoerythroblastosis in pre-PMF considered by the latter as one of the minor diagnostic criteria which seems unwarranted. In contrast to the revised 4^th edition, the majority of the microscopic images used for the WHO 5^th due to their low magnification and poor technique, do not highlight the diagnosis differences among these entities.