Genomics of T-lymphoblastic leukemia/lymphoma: 2023 SH/EAHP workshop proceedings

Abstract Objectives Recent molecular characterization of T‑lymphoblastic leukemia/lymphoma (T-ALL/LBL) has deepened our understanding of the pathogenesis and created a strong foundation for novel therapeutic strategies. Consequently, both the fifth edition of the World Health Organization and the International Consensus Classification systems for T-ALL/LBL have identified genomic subtypes, some as provisional entities. However, due to the challenges encountered in uncovering these alterations, molecular testing modalities and algorithms in clinical laboratory algorithms remain inconsistent or incomplete. Methods Cases from Session 8 of the 2023 Workshop of the Society for Hematopathology and the European Association for Haematopathology highlighted various T-ALL/LBL genetic subtypes and showcased phenotypic diversity even among individuals with identical genetic abnormalities. Results The data underscored the presence of significant genetic heterogeneity in T-ALL/LBL, highlighting the diagnostic value of specific genomic features for accurate classification, differentiation between immature and mature T-lymphoid neoplasms, and detection of underlying germline predisposition disorders. Further, the range of available standard molecular testing methodologies, including ancillary immunohistochemical studies, was discussed. Conclusions A comprehensive standardized testing of genomic abnormalities will advance T-ALL/LBL characterization in future classification systems, as underscored by the cases submitted to Session 8 of SH2023. The genetic heterogeneity underscores the need for personalized therapies that target driver genomic abnormalities.