Triple-hit TdT-positive high-grade B-cell lymphoma mimicking B-lymphoblastic lymphoma and exhibiting immunophenotypic change at relapse.

Abstract

Terminal deoxynucleotidyl transferase (TdT)-positive high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements ("double/triple-hit" lymphoma) is a rare, aggressive malignancy that often mimics B-lymphoblastic lymphoma (B-LBL), making accurate diagnosis challenging but clinically critical. We report the case of a 63-year-old female with triple-hit HGBCL involving the duodenum, initially presenting with blastoid morphology and a B-LBL-like immunophenotype: TdT(+), CD10(+), CD20(-), BCL6(-), and CD45dim. However, negativity for CD34 and other features inconsistent with B-LBL, such as MUM-1 positivity and cytoplasmic immunoglobulin expression, were also present. Fluorescence in situ hybridization confirmed MYC, BCL2, and BCL6 rearrangements. Despite an initial response to the hyper-CVAD/MA regimen, the patient subsequently relapsed. Relapse biopsies confirmed persistent triple-hit status and clonal identity via IgH gene rearrangement analysis. Unexpectedly, however, the immunophenotype at relapse had changed significantly, with tumor cells becoming TdT(-), CD20(+), and BCL6(+), while remaining CD10(+). Ultimately, the patient died of the disease despite receiving salvage therapies. To our knowledge, this is the first reported case of TdT-positive HGBCL demonstrating loss of TdT expression alongside other immunophenotypic changes at relapse. This case highlights the potential for significant phenotypic change in this rare HGBCL subtype and the importance of comprehensive immunophenotypic and genetic analysis at both diagnosis and relapse for accurate classification and management, particularly in distinguishing it from B-LBL.