Oncogenic Role of BCL6 Rearrangement: A Focus on Follicular and Marginal Zone Lymphomas.

The BCL6 gene is a transcriptional regulator essential for germinal center B-cell function, modulating their activation, survival, cell cycle, and differentiation into plasma or memory B-cells. In indolent B-cell lymphomas, particularly follicular lymphoma and a subset of marginal zone lymphomas, BCL6 rearrangements are increasingly recognized as recurrent but heterogeneous events. In follicular lymphoma, their clinicopathologic significance differs according to the BCL2 status. While BCL6 rearrangements have limited impact in conventional BCL2-rearranged follicular lymphoma, BCL2-negative/BCL6-rearranged follicular lymphoma frequently display atypical morphologic, immunophenotypic, and molecular features, including partial overlap with nodal marginal zone lymphoma. These cases may show reduced expression of germinal center markers, plasmacytic or marginal zone differentiation, and mutational profiles overlapping with MZL, making their classification challenging. Altogether, current data suggest that BCL6-rearranged indolent B-cell lymphomas do not represent a single entity but rather a heterogeneous biological spectrum spanning germinal center and post-germinal center features. Understanding these overlaps is essential for improving diagnostic accuracy and refining the classification of indolent B-cell lymphomas.