The expanding spectrum of T-cell lymphomas with follicular helper T-cell phenotype and implications for differential diagnoses: A report of the 2023 SH/EA4HP Lymphoma Workshop

Abstract

Objectives The 2023 Society of Hematopathology/European Association for Haematopathology Workshop on Progress in Peripheral T- and NK-Cell Lymphomas addressed challenges in diagnosis, biomarkers, and molecular pathogenesis. Methods Session 1 of the workshop focused on T-follicular helper (TFH) lymphomas and related entities. Sixty-one cases were submitted, and their histology, phenotype, and genetics were reviewed. Results The panelists confirmed 46 cases as TFH lymphomas, more commonly angioimmunoblastic type than follicular or not otherwise specified. A small subset of patients were young adults. Expected immunophenotypic profile, with expression of pan T-cell markers and TFH-specific markers with subtle differences between the histologic subtypes was observed. Genetic analyses revealed classic genetic alterations associated with these tumors, including frequent mutations in epigenetic modifiers (eg, TET2, DNMT3A, and IDH2) and RHOA. A broad spectrum of clonal B-cell proliferations was associated with TFH lymphomas, including polymorphic proliferations to large B-cell lymphoma-like expansions, often associated with Epstein-Barr virus. The remaining 15 cases were reclassified with alternative diagnoses, underscoring the diagnostic challenges and complexity in distinguishing TFH lymphomas from other entities. Conclusions The cases highlighted the clinical and biological heterogeneity and complexity of TFH lymphomas and provided a framework for pathology workup and diagnosis as well as future research.