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

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• Primary thyroid lymphomas, including extranodal marginal zone lymphoma (EMZL) and diffuse large B-cell lymphoma (DLBCL), commonly arise from Hashimoto's thyroiditis (HT).
• The evolution of these lymphomas and their relapse patterns are not fully understood, particularly the role of immune dysregulation in driving clonal B-cell evolution.

Purpose of the Study:

• To investigate the evolutionary mechanisms underlying primary thyroid lymphomas and their relapse.
• To identify shared mutational profiles between primary lesions, relapsed lymphomas, and background Hashimoto's thyroiditis.

Main Methods:

• Mutation profiling of 10 primary thyroid lymphoma cases.
• Analysis included cases with metachronous lymphomas, composite lymphomas, and paired lymphoma and HT biopsies.
• Comparative genomic analysis to identify shared and distinct mutations.

Main Results:

• Four cases of metachronous lymphomas showed divergent evolution from clonally related lymphoma precursor (CLP) cells, with some lesions sharing mutations and others distinct.
• One case demonstrated progression from the initial lymphoma to relapse.
• Two of four cases with paired lymphoma and HT biopsies exhibited shared mutations, suggesting involvement and divergent evolution from CLP cells.

Conclusions:

• Thyroid lymphoma relapse frequently arises from divergent evolution of premalignant clonal lymphoma precursor (CLP) cells.
• Understanding the evolution from CLP cells is crucial for comprehending thyroid lymphoma relapse.
• Shared mutations between thyroid lymphomas and HT indicate a common origin and evolutionary pathway.