53. The classification conundrum: Where do myeloid neoplasms belong?

Acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) have relied on the World Health Organization (WHO) system for classification. In 2022, two independent systems were proposed to replace the previous WHO fourth edition (WHO4): the WHO fifth edition (WHO5) and the International Consensus Classification (ICC) systems. Both use recurring genetic changes, disease biology and clinical features to categorize AML and MDS. To compare WHO5 and ICC, we reviewed cases of AML and MDS with reported cytogenetic, sequencing, and clinical data which were diagnosed at Vancouver General Hospital between 2016 and 2022. After applying each system to 446 total myeloid neoplasm cases, we defined 90 cases showing discrepancies between WHO5 and ICC. Under ICC, 28 cases are defined as AML with mutated TP53, while the corresponding category is absent in WHO5. The MDS/AML category put forth by ICC applies to 39 cases; these cases are defined as either MDS with biallelic TP53 mutations (MDS-biTP53), MDS with increased blasts (MDS-IB2), or MDS with fibrosis (MDS-f) under WHO5. Under ICC, 4 cases of AML with mutated RUNX1 and 4 cases of AML with isolated trisomy 8 are genetically defined, whereas these 8 cases are not genetically defined by WHO5. Under WHO5, 2 cases of MDS are upgraded to AML with mutated NPM1, but these cases do not meet the blast cut-off for AML according to ICC. Of the remaining, 10 cases of MDS have terminological differences, and 3 cases of MDS or AML are at the borderline of specific genetic criteria.