Secondary minimally differentiated acute leukemia with plasmacytoid dendritic cell differentiation (pDC-AML) following chemoradiotherapy for Ewing sarcoma in a child: biallelic EZH2 inactivation

The diagnosis of myeloid neoplasms with plasmacytoid dendritic cell (pDC) differentiation is challenging due to immunophenotypic overlap with BPDCN. We describe an 8-year-old boy with a history of Ewing sarcoma treated with chemotherapy and radiotherapy who developed acute myeloid leukemia (AML) two years later. Bone marrow met criteria for AML with minimal differentiation: blasts expressed CD34, CD117, CD33, and CD7 but lacked myeloperoxidase; scattered TCF4+ cells indicated a minor pDC component. Concurrently, 23.6% of pleural fluid cells exhibited a classic pDC immunophenotype (CD123+bright, CD304+, CD4+, HLA-DR+bright, CD56-, TCF4+ by immunohistochemistry). Genetic analysis revealed a complex karyotype with del(7q), biallelic EZH2 inactivation, 3q duplication involving MECOM, and PTPN11 mutation. This pediatric therapy-related case with a distinct genetic profile expands the spectrum of pDC-AML and highlights the diagnostic pitfall of CD123+/CD4+ immunophenotype in myeloid neoplasms with pDC differentiation.