A Review of the Pathological and Molecular Diagnosis of Primary Myelofibrosis

Primary myelofibrosis (PMF) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) that features clonal proliferation of atypical megakaryocytes and myeloid cells, fibrosis of the bone marrow, extramedullary hematopoiesis, and increased risk of leukemic transformation to acute myeloid leukemia (AML). With the widespread application of molecular studies, especially next generation sequencing (NGS), significant advances have reshaped our understanding of the molecular pathogenesis of PMF and the prognostic relevance of specific gene mutations. In this review, we summarize its clinicopathologic features, genetic and molecular findings, updated diagnostic criteria, and differential diagnosis. These updates have been incorporated into the 5th edition of the World Health Organization classification of Hematolymphoid Tumors (WHO-5th) and the 2022 International Consensus Classification (ICC), thereby improving diagnostic accuracy and risk stratification, both of which are essential for tailoring treatment strategies and enhancing patient outcomes.