Myeloid neoplasms with unusual patterns of disease evolution and progression other than acute leukemia: a European...

Myeloid neoplasms (MN) undergo dynamic clinical, morphologic, and molecular evolution over time. Although transformation to acute myeloid leukemia (AML) is the most widely recognized form of progression, MN may evolve through diverse, less well-recognized patterns. The European Bone Marrow Working Group dedicated a workshop at the XVII International Bone Marrow Course and Workshop in Salzburg, Austria, in 2025 to unusual patterns of MN evolution and progression other than acute leukemia. The submitted cases illustrate the remarkable phenotypic and genetic plasticity of MN. Recurrent patterns included acquisition of myelodysplastic features in myeloproliferative neoplasms (MPN); emergence or worsening of proliferative features, including monocytosis and neutrophilia, in MPN, myelodysplastic syndromes (MDS), and MDS/MPN; progressive myelofibrosis; extramedullary myeloid tumors; and histiocytic or dendritic cell outgrowths. These changes were frequently accompanied by clonal evolution and acquisition or expansion of additional genetic abnormalities. Importantly and as exemplified by a few workshop cases, apparent clinical progression may occasionally represent an independent second neoplasm or a reactive process rather than true progression of the original disease. These observations emphasize that follow-up evaluation of MN should extend beyond blast enumeration and incorporate clinical findings, morphology, immunophenotype, molecular genetics, and extramedullary manifestations. Changes in phenotype, morphology, immunophenotype, or genetic profile should generally be regarded as manifestations of disease evolution rather than, by themselves, criteria for reclassification into another MN subtype. The original disease entity should therefore be retained, while subsequent disease evolution, progression, transformation, lineage outgrowth, and extramedullary manifestations should be documented as part of an integrated diagnostic assessment.