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Background <p>Nodal T follicular helper cell lymphoma, angioimmunoblastic type (AITL), is a common peripheral AQ1T-cell lymphoma characterized by recurrent mutations in<i> TET2, IDH2, DNMT3A,</i> and <i>RHOA,</i> with <i>TET2</i> and <i>DNMT3A</i> 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.</p> Methods <p>Comprehensive 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.</p> Results <p>Molecular analysis revealed a shared <i>TET2</i> 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 <i>RHOA</i> mutation in AITL and <i>MYC</i> rearrangement with <i>ID3</i> mutation in BL.</p> Conclusion <p>This 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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年6月3日

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  • FNU Monika,
  • Hammad Tashkandi,
  • Mingfei Yan

摘要

Background

Nodal 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.

Methods

Comprehensive 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.

Results

Molecular 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.

Conclusion

This 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.