Primary thyroid B‐cell lymphoma: molecular insights into its clonal evolution and relapse

作者：Maria‐Myrsini Tzioni, Natsuko Watanabe, Zi Chen, Fangtian Wu, Ewelina Madej, Jasmine Makker, Sarah Guo, Ayoma D. Attygalle, Andrew Wotherspoon, Kiminori Sugino, Koichi Ito, Ming‐Qing Du · 发表于：The Journal of Pathology · 年份：2024 · DOI：10.1002/path.6380 · 被引用次数：7 · 研究领域：Lymphoma Diagnosis and Treatment、Thyroid Cancer Diagnosis and Treatment、Genetic factors in colorectal cancer

Primary thyroid lymphomas comprise largely extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) and diffuse large B-cell lymphoma (DLBCL), followed by follicular lymphoma (FL). They commonly develop from a background of Hashimoto's thyroiditis (HT), where dysregulated immune responses trigger autoreactive infiltrates and drive clonal B-cell evolution. To understand how these lymphomas and their relapse evolve, we investigated 10 cases by mutation profiling, including five with metachronous lymphomas [primary lymphoma (EMZL = 4, DLBCL = 1) with local relapse (EMZL = 3, DLBCL = 2)], one composite EMZL and Epstein-Barr virus (EBV)-positive DLBCL, and four lymphomas (EMZL = 3, FL = 1) with prior or subsequent biopsy showing HT. In four cases with metachronous lymphomas, both common and distinct variants were seen in the paired lesions, indicating their divergent evolution from clonally related lymphoma precursor (CLP) cells. In the remaining case with metachronous lymphomas, the relapsed lesion was progressed from the initial lymphoma. In the case with composite lymphoma, the EBV-positive DLBCL was transformed from EMZL. Finally, in the four cases with paired lymphoma and HT biopsies, two showed shared mutations between the paired lesions, indicating involvement and divergent evolution from CLP cells. Thyroid lymphoma relapse may frequently develop via divergent evolution from a CLP cell, which is likely premalignant. © 2024 The Author(s). The Journal of ...