Pediatric Pure Erythroid Leukemia: Diagnostic Challenges, Immunophenotypic Features, Molecular Pathogenesis, and Practical Diagnostic Approach

Pure erythroid leukemia (PEL), termed acute erythroid leukemia in the 2022 World Health Organization classification, is an uncommon and aggressive acute myeloid neoplasm in which immature erythroid precursors predominate within the marrow and show marked maturation arrest. Pediatric recognition remains challenging because adult PEL is usually defined by biallelic TP53 alteration and complex karyotype, whereas reported childhood disease encompasses NUP98-, NFIA-, CIC-, and other fusion-defined presentations. This structured narrative review summarizes classification, morphology, immunophenotype, molecular pathogenesis, genotype-phenotype heterogeneity, differential diagnosis, treatment, prognosis, measurable residual disease (MRD), and a practical diagnostic workflow. Evidence was weighted according to source type, with priority given to WHO and International Consensus Classification documents, multicenter pediatric cohorts, comparative molecular studies, and molecularly characterized case series. A pediatric PEL-specific treatment standard has not yet been established. Most reported children receive protocol-based therapy for acute myeloid leukemia, while hematopoietic stem-cell transplantation is considered according to adverse genetics, treatment response, MRD, relapse status, and extramedullary involvement. The largest pediatric cooperative-group dataset reported 5-year overall and event-free survival of approximately 20% for the PEL subset, although genotype-specific outcome estimates remain sparse. MRD assessment should combine baseline immunophenotypic documentation with molecular tracking when a stable fusion or mutation is available, and cerebrospinal fluid monitoring should be considered when central nervous system disease is documented. Integrated diagnosis and management require coordinated morphology, flow cytometry, immunohistochemistry, cytogenetics, DNA sequencing, and early RNA-based fusion testing. This approach should explicitly account for the limited evidence base underlying current recommendations.