AUTHOR=Marques-Piubelli Mario L. , Amador Catalina , Vega Francisco 

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

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1105651

DOI=10.3389/fonc.2023.1105651

ISSN=2234-943X

ABSTRACT=<p>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 <italic>PD-1<sup>hi</sup>, ICOS<sup>hi</sup>, CD40L<sup>hi</sup>, CD95<sup>hi</sup>, CTLA<sup>hi</sup>, CCR7<sup>lo</sup>, and CXCR5<sup>hi</sup></italic>. 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 (<italic>TET2</italic>, <italic>DNMT3A</italic>, <italic>IDH2</italic>), <italic>RHOA</italic>, 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.</p>