Clinical and molecular characteristics of extramedullary acute myeloid leukemias

Extramedullary deposits of acute myeloid leukemia (eAML), constitute an unusual presentation or complication of AML, which can occur in isolation (isolated eAML) or in the context of a fully-blown leukemic process (synchronous eAML) either at diagnosis or relapse [ 1 , 2 , 3 ]. This peculiar and rare variant of AML may be due to distinct biological features hypothesized to promote the homing of blasts to non-hematopoietic locations or/and be a result of specific molecular lesions, perhaps related to an invariant genotype [ 4 , 5 ]. So far, systematic studies of this phenomenon have been scarce despite the advances in molecular studies and next generation sequencing over the last decade. Furthermore, while recognized in the 2022 World Health Organization (WHO) classification, guidance with regard to prognosis and treatment for this unique entity was not included in the recent European Leukemia Network (ELN) 2022 AML guidelines [ 6 , 7 ]. Generally, the prognostic impact of eAML is unclear since none of the clinical and molecular prognostic tools looked at the effect of eAML on disease outcomes. Here, we took advantage of a large cohort of AML patients to investigate the clinical, molecular, and outcome features of patients with eAML. In addition, given the paucity of clinical data and randomized trials, we looked at the role of different treatment options in the management of this special entity, including isolated and synchronous eAML cases.