A retrospective review of myeloproliferative neoplasms and correlation of bone marrow morphological results with next generation sequencing profiles

Abstract

Background: Classification of Philadelphia negative (Ph-) myeloproliferative neoplasms (MPN) relies on the integration of peripheral blood counts, demonstration of driver mutations where possible and the interpretation of bone marrow aspirate and trephine morphology. Of these disorders, the distinction between essential thrombocythemia and prefibrotic myelofibrosis can be challenging. Objectives and methods: To assess reproducibility of the WHO classification for this group of MPNs and to assess the potential of utilising next generation sequencing (NGS) to assist with the diagnosis. This retrospective study was conducted at Pathwest QEII, Western Australia. Twenty cases of MPNs from 2017–2021 with an initial diagnosis or differential diagnosis of essential thrombocythaemia (ET), prefibrotic myelofibrosis (prePMF) and primary myelofibrosis (PMF) were centrally reviewed using a standardised proforma for the FBP parameters and defined morphologic criteria based on the WHO classification. NGS was performed to assess the variant allele frequencies (VAF) of driver mutations and the presence of additional mutations. Results: Fifteen cases were concordant with the initial morphological review. ET cases had a lower JAK2V617F VAF compared to PMF and fewer number of additional mutations. NGS was of limited use in the differentiation between ET and prePMF in the other five cases that were difficult to classify on morphological grounds. Conclusions: This study is limited by the small sample size but reflects practice in a diagnostic laboratory. In this study, the application of NGS was of limited use in further assisting the diagnosis of ET or prePMF where the strict WHO criteria are applied.