Pathologic and molecular insights in nodal T-follicular helper cell lymphomas

Mario L Marques-Piubelli; Catalina Amador; Francisco Vega

doi:10.3389/fonc.2023.1105651

Pathologic and molecular insights in nodal T-follicular helper cell lymphomas

Front Oncol. 2023 Jan 30:13:1105651. doi: 10.3389/fonc.2023.1105651. eCollection 2023.

Authors

Mario L Marques-Piubelli¹, Catalina Amador², Francisco Vega³

Affiliations

¹ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
² Division of Hematopathology, Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL, United States.
³ Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Abstract

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1^hi, ICOS^hi, CD40L^hi, CD95^hi, CTLA^hi, CCR7^lo, and CXCR5^hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular findings. The markers most frequently used to identify a TFH immunophenotype in paraffin-embedded tissue sections include PD-1, CXCL13, CXCR5, ICOS, BCL6, and CD10. These neoplasms feature a characteristic and similar, but not identical, mutational landscape with mutations in epigenetic modifiers (TET2, DNMT3A, IDH2), RHOA, and T-cell receptor signaling genes. Here, we briefly review the biology of TFH cells and present a summary of the current pathologic, molecular, and genetic features of nodal lymphomas. We want to highlight the importance of performing a consistent panel of TFH immunostains and mutational studies in TCLs to identify TFH lymphomas.

Keywords: angioimmunoblastic T cell lymphoma; follicular T helper; molecular and genetic profiling; next-generation sequencing; peripheral T cell lymphomas.

Publication types

Review