{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:09:36Z","timestamp":1773076176024,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Follicular lymphoma (FL), comprising a minor subset of primary thyroid lymphomas, is divided into two groups based on Bcl\u20102 expression and <jats:italic>IGH\u2010BCL2<\/jats:italic> translocation. The clinicopathological features exhibited by Bcl\u20102\u2010negative <jats:italic>IGH\u2010BCL2<\/jats:italic> translocation\u2010negative FL of the thyroid (Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>\u2013<\/jats:sup> tFL) are different from those of conventional FL; however, its lymphomagenesis remains unclear. Here, we collected samples from seven patients with Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>\u2013<\/jats:sup> tFL to investigate their epigenetic and genetic aberrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The immunohistochemical profiles of epigenetic modifiers and the methylation status of histones were examined, including EZH2, MLL2\/KMT2D, CBP\/CREBBP, EP300, H3K27me3 and H3K4me3, in Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<jats:sup>\u2013<\/jats:sup><\/jats:italic> tFL and Bcl\u20102\u2010positive <jats:italic>IGH\u2010BCL2<\/jats:italic> translocation\u2010positive FL of the thyroid (Bcl\u20102<jats:sup>+<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>+<\/jats:sup> tFL). Most Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>\u2013<\/jats:sup> tFLs retained the positivity of epigenetic modifiers and lower expression of H3K27me3, although Bcl\u20102<jats:sup>+<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>+<\/jats:sup> tFLs exhibited aberrant immunohistochemical patterns of EZH2 and CBP\/CREBBP and overexpression of H3K27me3. Samples from seven cases were further analysed using targeted sequencing, focusing on the exons of 409 key tumour suppressor genes and oncogenes. Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>\u2013<\/jats:sup> tFLs do not have pathogenic mutations of epigenetic modifiers, such as <jats:italic>EZH2<\/jats:italic>, <jats:italic>MLL2\/KMT2D<\/jats:italic>, <jats:italic>MLL3\/KMT2C<\/jats:italic>, <jats:italic>EP300<\/jats:italic> and <jats:italic>ARID1A<\/jats:italic>, which have been reported in FLs in the literature, whereas Bcl\u20102<jats:sup>+<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>+<\/jats:sup> tFLs are probably pathogenic\/pathogenic missense mutations or frameshift mutations of these genes. Additionally, novel mutations in <jats:italic>TET2<\/jats:italic> and <jats:italic>EP400<\/jats:italic> were detected in Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>\u2013<\/jats:sup> tFLs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Different genetic and epigenetic abnormalities might be involved in the oncogenesis of Bcl\u20102<jats:sup>\u2013<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>\u2013<\/jats:sup> tFLs from Bcl\u20102<jats:sup>+<\/jats:sup>\/<jats:italic>IGH\u2010BCL2<\/jats:italic><jats:sup>+<\/jats:sup> tFLs and other FLs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14378","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T06:35:56Z","timestamp":1617863756000},"page":"521-532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bcl\u20102\u2010negative <i>IGH\u2010BCL2<\/i> translocation\u2010negative follicular lymphoma of the thyroid differs genetically and epigenetically from Bcl\u20102\u2010positive <i>IGH\u2010BCL2<\/i> translocation\u2010positive follicular lymphoma"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-760X","authenticated-orcid":false,"given":"Yuichiro","family":"Hamamoto","sequence":"first","affiliation":[{"name":"Department of Diagnostic Pathology and Cytology Osaka International Cancer Institute Osaka Japan"},{"name":"Department of Pathology Osaka University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoji","family":"Kukita","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Pathology Osaka International Cancer Institute Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Cytology Osaka International Cancer Institute Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Kurashige","sequence":"additional","affiliation":[{"name":"Department of Pathology Osaka University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Masaie","sequence":"additional","affiliation":[{"name":"Department of Hematology Osaka International Cancer Institute Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Fuji","sequence":"additional","affiliation":[{"name":"Department of Hematology Osaka International Cancer Institute Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Osaka International Cancer Institute Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichiro","family":"Honma","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Cytology Osaka International Cancer Institute Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Wakasa","sequence":"additional","affiliation":[{"name":"Diagnostic Pathology and Laboratory Medicine Kindai University Nara Hospital Nara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Hanamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Kindai University Nara Hospital Nara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuyoshi","family":"Hirokawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Cytology Kuma Hospital Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayana","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Cytology Kuma Hospital Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Morii","sequence":"additional","affiliation":[{"name":"Department of Pathology Osaka University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0055-8149","authenticated-orcid":false,"given":"Shin\u2010ichi","family":"Nakatsuka","sequence":"additional","affiliation":[{"name":"Department of Pathology Sakai City Medical Center Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"e4088","article-title":"Primary thyroid lymphoma: an analysis of the National Cancer 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