{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:37:25Z","timestamp":1790789845419,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Department of Pathology, University of Iowa Hospitals and Clinics, Iowa"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Follicular helper T cell (TFH) markers are expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma of the TFH phenotype (PTCL-TFH). However, differential expression and coexpression of these markers in benign and other malignant lymphoid proliferations have not been well studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed programmed death-1 (PD-1), C-X-C motif chemokine ligand 13 (CXCL13), inducible costimulator (ICOS), CD10, and B-cell lymphoma 6 protein (BCL-6) immunohistochemistry on AITL, PTCL not otherwise specified (PTCL-NOS), PTCL-TFH, T-cell or histiocyte-rich large B-cell lymphoma (THRLBCL), classic Hodgkin lymphoma (CHL), atypical paracortical hyperplasia (PCH), progressive transformation of germinal centers (PTGC), and reactive follicular hyperplasia (RFH).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CXCL13 and ICOS were more sensitive but less specific for AITL than PD-1, CD10, and BCL-6. Moreover, 74% of AITL (none of PTCL-NOS or PTCL-TFH) coexpressed more than 2 TFH markers. In background T cells of THRLBCL, 70% of cases coexpressed more than 1 marker. The background T cells of CHL expressed all TFH markers except CD10 in all cases. In addition, 13% of PCH cases coexpressed more than 1 marker. In RFH and PTGC, all markers were expressed mainly in germinal centers with rare extrafollicular staining.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>AITL, PTCL-NOS, and PTCL-TFH show differential expression of TFH markers. AITL frequently coexpresses more than 2 TFH markers. TFH markers can be expressed in PCH and in background T cells of THRLBCL and CHL. Consequently, caution should be used before a diagnosis of AITL is established, particularly with limited samples.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqaa249","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T20:11:43Z","timestamp":1604088703000},"page":"409-426","source":"Crossref","is-referenced-by-count":18,"title":["Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin"],"prefix":"10.1093","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1271-4110","authenticated-orcid":false,"given":"Ibrahim","family":"Abukhiran","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Iowa Hospitals and Clinics Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei I","family":"Syrbu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Hospitals and Clinics Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-9914","authenticated-orcid":false,"given":"Carol J","family":"Holman","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Hospitals and Clinics Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"2021080509102338900_CIT0001","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4049\/jimmunol.173.1.68","article-title":"T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1\/Th2 effector cells that provide help for B cells","volume":"173","author":"Chtanova","year":"2004","journal-title":"J Immunol."},{"key":"2021080509102338900_CIT0002","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1182\/blood-2004-03-1206","article-title":"Unique gene expression program of human germinal center T helper cells","volume":"104","author":"Kim","year":"2004","journal-title":"Blood."},{"key":"2021080509102338900_CIT0003","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1136\/jcp.2010.084459","article-title":"Expression of follicular helper T cell markers in nodal peripheral T cell lymphomas: a tissue microarray analysis of 162 cases","volume":"64","author":"Zhan","year":"2011","journal-title":"J Clin Pathol."},{"key":"2021080509102338900_CIT0004","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.4049\/jimmunol.170.3.1257","article-title":"Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production","volume":"170","author":"Brown","year":"2003","journal-title":"J Immunol."},{"key":"2021080509102338900_CIT0005","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/ni1165","article-title":"Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4","volume":"6","author":"Probst","year":"2005","journal-title":"Nat Immunol."},{"key":"2021080509102338900_CIT0006","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood-2004-04-1596","article-title":"The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation","volume":"105","author":"Riley","year":"2005","journal-title":"Blood."},{"key":"2021080509102338900_CIT0007","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nri727","article-title":"The B7-CD28 superfamily","volume":"2","author":"Sharpe","year":"2002","journal-title":"Nat Rev Immunol."},{"key":"2021080509102338900_CIT0008","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0165-2478(02)00088-3","article-title":"Microanatomical localization of PD-1 in human tonsils","volume":"83","author":"Iwai","year":"2002","journal-title":"Immunol Lett."},{"key":"2021080509102338900_CIT0009","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1097\/01.pas.0000209855.28282.ce","article-title":"Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma","volume":"30","author":"Dorfman","year":"2006","journal-title":"Am J Surg Pathol."},{"key":"2021080509102338900_CIT0010","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/PAS.0b013e3181cc7e79","article-title":"PD-1 expression in T-cell lymphomas and reactive lymphoid entities: potential overlap in staining patterns between lymphoma and viral lymphadenitis","volume":"34","author":"Krishnan","year":"2010","journal-title":"Am J Surg Pathol."},{"key":"2021080509102338900_CIT0011","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1001\/archdermatol.2012.2089","article-title":"Differential expression of programmed death-1 (PD-1) in S\u00e9zary syndrome and mycosis fungoides","volume":"148","author":"Cetin\u00f6zman","year":"2012","journal-title":"Arch Dermatol."},{"key":"2021080509102338900_CIT0012","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1097\/DAD.0b013e31825b26d1","article-title":"CD4\/CD8 double negative mycosis fungoides with PD-1 (CD279) expression\u2014a disease of follicular helper T-cells?","volume":"34","author":"Kempf","year":"2012","journal-title":"Am J Dermatopathol."},{"key":"2021080509102338900_CIT0013","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow","year":"2017","edition":"Revised 4th ed"},{"key":"2021080509102338900_CIT0014","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1097\/00000478-200604000-00009","article-title":"Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells","volume":"30","author":"Dupuis","year":"2006","journal-title":"Am J Surg Pathol."},{"key":"2021080509102338900_CIT0015","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1097\/PAS.0b013e31817f123e","article-title":"Peripheral T-cell lymphoma with follicular T-cell markers","volume":"32","author":"Rodr\u00edguez-Pinilla","year":"2008","journal-title":"Am J Surg Pathol."},{"key":"2021080509102338900_CIT0016","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.3324\/haematol.10864","article-title":"Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma","volume":"92","author":"Roncador","year":"2007","journal-title":"Haematologica."},{"key":"2021080509102338900_CIT0017","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1309\/AJCP62WRKERPXDRT","article-title":"Germinal-center T-helper-cell markers PD-1 and CXCL13 are both expressed by neoplastic cells in angioimmunoblastic T-cell lymphoma","volume":"131","author":"Yu","year":"2009","journal-title":"Am J Clin Pathol."},{"key":"2021080509102338900_CIT0018","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/modpathol.3800625","article-title":"Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified","volume":"19","author":"Grogg","year":"2006","journal-title":"Mod Pathol."},{"key":"2021080509102338900_CIT0019","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow","year":"2008"},{"key":"2021080509102338900_CIT0020","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1182\/blood-2006-10-055145","article-title":"The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells","volume":"109","author":"de Leval","year":"2007","journal-title":"Blood."},{"key":"2021080509102338900_CIT0021","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/his.12251","article-title":"Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward\u2014report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology","volume":"64","author":"Attygalle","year":"2014","journal-title":"Histopathology."},{"key":"2021080509102338900_CIT0022","doi-asserted-by":"crossref","first-page":"44960","DOI":"10.18632\/oncotarget.16680","article-title":"Mechanisms of PD-1\/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies","volume":"8","author":"Gravelle","year":"2017","journal-title":"Oncotarget."},{"key":"2021080509102338900_CIT0023","doi-asserted-by":"crossref","first-page":"105999","DOI":"10.1016\/j.intimp.2019.105999","article-title":"Prognostic and clinicopathological significance of PD-1\/PD-L1 expression in the tumor microenvironment and neoplastic cells for lymphoma","volume":"77","author":"Xie","year":"2019","journal-title":"Int Immunopharmacol."}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/156\/3\/409\/39576625\/aqaa249.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/156\/3\/409\/39576625\/aqaa249.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:18:24Z","timestamp":1628155104000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/156\/3\/409\/6148885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2,24]]},"published-print":{"date-parts":[[2021,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqaa249","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9,1]]},"published":{"date-parts":[[2021,2,24]]}}}