Progression of follicular lymphoma and related entities: Report from the 2021 SH/EAHP Workshop

Abstract Objectives The 2021 Society for Hematopathology and European Association for Haematopathology Workshop addressed the molecular and cytogenetic underpinnings of transformation and transdifferentiation in lymphoid neoplasms. Methods Session 4, “Transformations of Follicular Lymphoma,” and session 5, “Transformations of Other B-Cell Lymphomas,” included 45 cases. Gene alteration analysis and expression profiling were performed on cases with submitted formalin-fixed, paraffin embedded tissue. Results The findings from session 4 suggest that “diffuse large B-cell lymphoma/high-grade B-cell lymphoma with rearrangements of MYC and BCL2” is a distinct category arising from the constraints of a preexisting BCL2 translocation. TdT expression in aggressive B-cell lymphomas is associated with MYC rearrangements, immunophenotypic immaturity, and a dismal prognosis but must be differentiated from lymphoblastic ­lymphoma. Cases in session 5 illustrated unusual morphologic and immunophenotypic patterns of transformation. Additionally, the findings support the role of cytogenetic abnormalities—specifically, MYC and NOTCH1 rearrangements—as well as single gene alterations, including TP53, in transformation. Conclusions Together, these unique cases and their accompanying molecular and cytogenetic data suggest potential mechanisms for and unusual patterns of transformation in B-cell lymphomas and indicate numerous opportunities for further study.