Shared clonal origin of angioimmunoblastic T-cell lymphoma and Burkitt lymphoma arising through divergent evolution from a common precursor.

backgroundNodal T follicular helper cell lymphoma, angioimmunoblastic type (AITL), is a common peripheral AQ1T-cell lymphoma characterized by recurrent mutations in TET2, IDH2, DNMT3A, and RHOA, with TET2 and DNMT3A mutations frequently arising in early hematopoietic stem and progenitor cells (HSPCs) as clonal hematopoiesis (CH). In addition to its well-established association with secondary myeloid neoplasms, AITL is complicated by secondary B-cell lymphomas in up to 10-23% of cases, often associated with EBV infection. However, the clonal relationship between AITL, CH, and associated B-cell lymphomas remains less well understood. We report a rare case of an elderly male who developed AITL followed by EBV-positive Burkitt lymphoma (BL) three years later.

methodsComprehensive histopathologic evaluation, immunohistochemistry, flow cytometry, fluorescence in situ hybridization, and next-generation sequencing were performed on both lymphoma specimens and on a staging bone marrow sample.

resultsMolecular analysis revealed a shared TET2 p.Q962* mutation present at high variant allele frequencies in both the AITL and BL, which was also detected at low level in the bone marrow which showed no evidence of neoplasia, consistent with underlying CH. Each lymphoma harbored additional disease-characteristic genetic alterations, including RHOA mutation in AITL and MYC rearrangement with ID3 mutation in BL.

conclusionThis case establishes the shared clonal origin between AITL and BL arising in the setting of CH and provides additional biological insight into the development of B-cell lymphoma associated with AITL.