Problems and pitfalls regarding WHO-defined diagnosis of early/prefibrotic primary myelofibrosis versus essential thrombocythemia

Reproducibility and clinical usefulness of the WHO classification of chronic myeloproliferative neoplasm (MPN) persist to be a controversial issue. Major arguments are focused on the critical impact of histopathology, particularly concerning the distinction between essential thrombocythemia (ET) versus early/prefibrotic primary myelofibrosis (PMF). Regarding bone marrow morphology, WHO guidelines strictly require the recognition of characteristic histological patterns based on standardized features and a consensus of clinical and molecular-genetic data. Molecular-genetic findings as JAK2V617F, may aid to exclude reactive thrombocytosis, although in ET and PMF only 50-60% of the cases show these aberrations. Considerable doubts over the existence of early/prefibrotic PMF have been expressed with the consequence to include this entity in the ET category. On the other hand, it has to be argued that some of the critical studies failed to adhere very strictly to the WHO guidelines. Contrasting this situation, recently published retrospective and prospective clinico-pathological studies featuring the WHO criteria provided an important information on disease outcomes supporting the existence of early/prefibrotic PMF as a distinct clinico-pathologic entity in patients presenting clinically with ET. Therefore, this controversy suggests a scientific project, including the community of pathologists and hematologists, for providing sound, objective and reproducible criteria for diagnosing early/prefibrotic PMF.