{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:50:53Z","timestamp":1790985053571,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Germ cell neoplasia in situ (GCNIS) is the precursor of GCNIS\u2010derived testicular germ cell tumours, including seminomas and non\u2010seminomas. Most non\u2010seminomas show mixed histology, often including components of seminoma. A small subset presents as pure non\u2010seminomatous germ cell tumors. In these neoplasms, the absence of invasive seminoma. raises the possibility that reprogramming to non\u2010seminoma may occur at an early in\u2010situ stage (i.e., within the spermatogonial niche). This study examined GCNIS associated with pure embryonal carcinoma (EC) and postpubertal\u2010type yolk sac tumour (YST) using immunohistochemistry for transcription factors characteristic of GCNIS\/seminoma, EC, and YST phenotypes to determine if reprogramming to non\u2010seminoma occurs within the spermatogonial niche.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GCNIS associated with pure testicular YST and EC was assessed using OCT4, FOXA2 (only YST), CD30 (only EC), SOX2 (only EC), SOX17, and NANOG immunohistochemistry. Adjacent foci of intratubular and invasive tumour were also evaluated, if present.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty\u2010seven pure non\u2010seminomas (63 EC, 4 YST) were evaluated. In all cases, GCNIS expressed OCT4, SOX17, and NANOG. GCNIS associated with EC was consistently negative for CD30 and SOX2, and GCNIS associated with YST was consistently negative for FOXA2. Adjacent invasive EC (62\/67 cases) and intratubular EC (19\/67) showed the classic EC immunophenotype: OCT4+\/NANOG+\/SOX17\u2013\/SOX2+\/CD30+. Similarly, invasive YST adjacent to GCNIS was\u00a0OCT4\u2013\/NANOG\u2013\/SOX17+\/FOXA2+.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Assessment of transcription factors involved in the induction and maintenance of EC and YST phenotypes suggests that, in pure non\u2010seminomas, reprogramming occurs outside the spermatogonial niche.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70160","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:21:06Z","timestamp":1776334866000},"page":"303-311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunophenotypic assessment of pure embryonal carcinoma and yolk sac tumour suggests that reprogramming to non\u2010seminoma occurs outside the spermatogonial niche"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-243X","authenticated-orcid":false,"given":"Daisy","family":"Maharjan","sequence":"first","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3231-6870","authenticated-orcid":false,"given":"Kv\u011btoslava","family":"Michalov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology Charles University, Faculty of Medicine in Plzen, Biopticka Laborator, Ltd  Plzen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Joao","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Oncology Institute of Porto  Porto Portugal"},{"name":"Cancer Biology and Epigenetics Group, CI\u2010IPOP  Porto Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0745-2160","authenticated-orcid":false,"given":"Jennifer","family":"Gordetsky","sequence":"additional","affiliation":[{"name":"Department of Pathology and Urology Vanderbilt University Medical Center, Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-2368","authenticated-orcid":false,"given":"Fiona","family":"MacLean","sequence":"additional","affiliation":[{"name":"Douglass Hanly Moir Pathology  North Ryde New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7233-2361","authenticated-orcid":false,"given":"Ankur R","family":"Sangoi","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford Medical Center  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5474-8696","authenticated-orcid":false,"given":"Daniel","family":"Berney","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers &amp; Biotherapeutics Barts Cancer Institute, Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-2567","authenticated-orcid":false,"given":"Chia\u2010Sui","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Ricci","sequence":"additional","affiliation":[{"name":"Pathology Unit, DIAP\u2010Dipartimento Interaziendale anatomia patologica di Bologna Maggiore Hospital\u2010AUSL Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-8134","authenticated-orcid":false,"given":"Adeboye O","family":"Osunkoya","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-4881","authenticated-orcid":false,"given":"Maria Rosaria","family":"Raspollini","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital Careggi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-9102","authenticated-orcid":false,"given":"Geert JLH","family":"van Leenders","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad T","family":"Idrees","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Ann","family":"Baldridge","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-2496","authenticated-orcid":false,"given":"Thomas M","family":"Ulbright","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-6331","authenticated-orcid":false,"given":"Andres 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EGF and FGF4 synergistically induce differentiation of the seminoma cell line TCam\u20102 into a cell type resembling mixed non\u2010seminoma","volume":"34","author":"Nettersheim D","year":"2011","journal-title":"Int. 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