Diagnosis of TP53-mutated myeloid disease by the ICC and WHO 5th Edition Classifications

The International Consensus (ICC) and World Health Organization 5th edition (WHO5) classifications introduced new but differing categories of myeloid disease defined by TP53 mutations. We reviewed a cohort of 188 cases of TP53-mutated myeloid disease to determine how diagnoses and outcomes differ between the two classifications. Overall, 120 (64%) cases were classified differently by the ICC and WHO5, including 24/80 (30%) cases with <20% blasts. These cases were discrepantly categorized primarily due to inclusion of complex karyotype (CK) as a surrogate for biallelic TP53 inactivation only in the ICC. However, there were no significant differences in clinicopathologic characteristics or overall survival between cases categorized as TP53-mutated disease by both classifications and those with a single TP53 mutation and CK, suggesting that CK reliably identifies TP53-mutated cases with biallelic TP53 inactivation. The majority of cases of AML (96/102; 94%) were discrepantly diagnosed between the ICC and WHO5 due to the introduction of AML with mutated TP53 as a distinct category only in the ICC. Nearly all of these were instead diagnosed as AML, myelodysplasia-related (AML, MR) by WHO5. However, when compared to a separate cohort of patients with AML, MR without TP53 mutations, patients with TP53-mutated AML showed a distinct genetic profile and significantly worse overall survival, supporting the inclusion of AML with mutated TP53 as a distinct disease category. Overall, our results show that a significant percentage of TP53-mutated myeloid disease is classified differently by the ICC and WHO5 and highlight areas to address in future classification systems.