How Many Tests Does It Take to Diagnose a Triple-Hit B-Lymphoblastic Lymphoma? (Hint, It's A Lot)

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is a precursor B-cell neoplasm that often harbors specific cytogenetic/molecular abnormalities with distinctive clinical, phenotypic, and prognostic characteristics. Subcategorization of B-ALL/LBL therefore requires extensive cytogenetic and/or molecular testing to determine the appropriate classification and therapeutic interventions for these patients. Herein, we present a case of a 17-year-old young woman diagnosed with B-LBL harboring not only an IGH::MYC rearrangement but also BCL2 and BCL6 rearrangements (so-called "triple-hit") and somatic biallelic TP53 inactivation. MYC rearrangements are relatively rare in B-ALL/LBL, and the identification of a "triple-hit" elicited an initial diagnostic dilemma. However, a multimodal approach allowed for the classification of this complex case and helped guide selection of an appropriate therapeutic regimen.