Moreover, both the WHO and ICC define cytogenetic and genetic changes almost always associated with antecedent MDS (Fig. 2A–B), while the cytogenetic profile has not drastically changed with a few exceptions, mutations in ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, or ZRSR2 now define AML with myelodysplasia-related gene mutations given the high prevalence of these mutations in MDS; RUNX1 mutations are also considered MDS-defining by the ICC but not by the WHO [25–28]. This evidence concerns the gene EZH2 and intrahepatic cholangiocarcinoma.