Systemic mastocytosis with an associated myeloid neoplasm: Report from the XVI European Bone Marrow Working Group...

Systemic mastocytosis with an associated myeloid neoplasm (SM-AMN) represents a diagnostic challenge. The first section of the XVI European Bone Marrow Working Group Workshop, held in Barcelona, Spain, in 2023, focused on such cases. Three main lessons were learned from the workshop. First, both the SM and the AMN components can mask each other. Second, because of their overlapping clinical and laboratory findings, it is usually impossible to recognize advanced systemic mastocytosis within an SM-AMN. In other words, unless the International Consensus Classification "C" findings were clearly caused by the SM, for purposes of classification, the SM component was regarded as not advanced. The distinction between indolent and smoldering SM was impossible, but the presence of mast cell leukemia as the SM component is usually recognizable and should be reported. Finally, the presence of myeloid gene mutations (other than KIT) were strongly associated with SM-AMN. These variations include SRFS2-p95, biallelic (double) TET2 or a TET2 mutation combined with an SRSF2 variation to identify chronic myelomonocytic leukemia associated with SM. Additional diagnostic issues included disease progression in the SM or the AMN component, the distinction between SM-AMN and acute myeloid leukemia with partial mast cell differentiation (aka, myelomastocytic leukemia), and rare types of disease proliferations occurring in SM-AMN.