Erythroblastic sarcoma with biallelic TP53 mutations and novel NUP214:: ABL1-new finding in erythroblastic...

NUP214::ABL1 generates a fusion protein with constitutively activated tyrosine kinase activity and is present in rare T-lymphoblastic leukemia (ALL), B-ALL, and in rare cases of myelodysplastic neoplasm/acute myeloid leukemia (MDS/AML). Here, we for the first time reported NUP214::ABL1 in a case of erythroblastic sarcoma (ES), a rare extramedullary form of acute erythroid leukemia (AEL). A 55-year-old female with a reported three-year history of MDS presented with worsening lower extremity paresthesia. Magnetic resonance imaging revealed an intraspinal T2-T4 extradural mass. Examination of the mass biopsy supported by extensive immunoprofiling was diagnostic of ES. Fluorescence in situ hybridization (FISH) identified concurrent deletions of 5p15.2 and 5q31 (likely monosomy 5), trisomy 8, and deletion of 7q31 while absent for translocations included in AML FISH panel. Next-generation sequencing (NGS) including DNA (406 genes) and RNA (265 genes) panels revealed NUP214::ABL1 (N31; A2) and TP53 I50fs*2 (VAF 85.9%). The patient died approximately two weeks after the ES diagnosis. This informative case emphasizes the importance for pathologists to be familiar with ES as a rare extramedullary form of AEL and a potential transformation from MDS. It is critical to apply comprehensive studies including cytogenetics/FISH and NGS in rendering prompt diagnosis for optimal management.