{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:24:27Z","timestamp":1787358267541,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["MFAG 2021 \u2013 ID 26319"],"award-info":[{"award-number":["MFAG 2021 \u2013 ID 26319"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The distinction between ovarian immature teratoma (IT) and mature teratoma (MT) relies on the identification of immature neuroectodermal tissue in the former, a task that may be challenging in some tumours and carries significant prognostic and therapeutic implications. SRY\u2010box transcription factor 2 (SOX2) has been proposed as a marker of immature neuroepithelium, although its expression in mature components of ovarian teratomas has not been systematically investigated. We aimed to assess the diagnostic value and limitations of SOX2, in comparison with SALL4, in differentiating immature from mature neuroectodermal elements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We retrospectively analysed a multicentric cohort of 61 ovarian teratomas (52 MTs and 9 ITs). SOX2 and SALL4 immunohistochemical expression was evaluated across all tissue components with correlation to detailed morphological assessment. SOX2 showed diffuse expression in both immature neuroepithelium and mature neuroectodermal tissues, including glia and ependymal structures, as well as a characteristic layer\u2010restricted pattern in retinal tissue, while cerebellar tissue was consistently negative; some non\u2010neural mature epithelial tissues were also positive. SALL4 expression was variably positive in immature neuroectodermal components (specifically in neuroectodermal rosettes) and was absent in all mature components. Notably, heterogeneous SOX2 expression in rosette\u2010like structures prompted systematic morphological reassessment, leading to reclassification of 5\/9 (55.6%) cases initially diagnosed as IT into MT. These findings highlight that SOX2 expression alone may represent a significant diagnostic pitfall, particularly in distinguishing immature neuroepithelium from mature ependymal rosettes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SOX2 is a sensitive marker of neuroectodermal lineage but does not discriminate between immature and mature elements. Its interpretation requires integration with morphology and SALL4 expression to avoid overdiagnosis and inappropriate tumour classification and grading of ITs. A pattern\u2010based approach to SOX2 staining may improve diagnostic accuracy in ovarian teratomas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70264","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T23:40:35Z","timestamp":1787355635000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pattern\u2010based interpretation of\n                    <scp>SOX2<\/scp>\n                    expression in ovarian teratomas: avoiding diagnostic pitfalls in the distinction between immature and mature neuroectodermal elements"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8560-1925","authenticated-orcid":false,"given":"Agnese","family":"Orsatti","sequence":"first","affiliation":[{"name":"Pathology Unit, DIAP\u2010Dipartimento Interaziendale di Anatomia Patologica di Bologna Maggiore Hospital\u2010AUSL  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8556-8756","authenticated-orcid":false,"given":"Caterina","family":"Ravaioli","sequence":"additional","affiliation":[{"name":"Pathology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2506-7239","authenticated-orcid":false,"given":"Marco","family":"Grillini","sequence":"additional","affiliation":[{"name":"Pathology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Franchini","sequence":"additional","affiliation":[{"name":"Pathology Unit, DIAP\u2010Dipartimento Interaziendale di Anatomia Patologica di Bologna Maggiore Hospital\u2010AUSL  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Oncology Institute of Porto (IPOP)  Porto Portugal"},{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (GEBC CI\u2010IPOP) Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (P.CCC)  Porto Portugal"},{"name":"Department of Pathology and Molecular Immunology, ICBAS\u2010School of Medicine and Biomedical Sciences University of Porto (ICBAS\u2010UP)  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-5911","authenticated-orcid":false,"given":"Andres M.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-3631","authenticated-orcid":false,"given":"Veronica","family":"Mollica","sequence":"additional","affiliation":[{"name":"Medical Oncology IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7143-9091","authenticated-orcid":false,"given":"Claudio","family":"Zamagni","sequence":"additional","affiliation":[{"name":"Addarii Medical Oncology IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-6531","authenticated-orcid":false,"given":"Pierandrea","family":"De Iaco","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna  Bologna Italy"},{"name":"Division of Gynecologic Oncology IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-4772","authenticated-orcid":false,"given":"Anna Myriam","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna  Bologna Italy"},{"name":"Division of Gynecologic Oncology IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-150X","authenticated-orcid":false,"given":"Michelangelo","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Pathology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-6682","authenticated-orcid":false,"given":"Giovanni","family":"Tallini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna  Bologna Italy"},{"name":"Solid Tumor Molecular Pathology Laboratory IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-4370","authenticated-orcid":false,"given":"W. Glenn","family":"McCluggage","sequence":"additional","affiliation":[{"name":"Department of Pathology Belfast Health and Social Care Trust  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-4195","authenticated-orcid":false,"given":"Costantino","family":"Ricci","sequence":"additional","affiliation":[{"name":"Pathology Unit, DIAP\u2010Dipartimento Interaziendale di Anatomia Patologica di Bologna Maggiore Hospital\u2010AUSL  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-5135","authenticated-orcid":false,"given":"Antonio","family":"De Leo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna  Bologna Italy"},{"name":"Solid Tumor Molecular Pathology Laboratory IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1097\/01.AOG.0000216004.22588.ce","article-title":"Incidence and survival rates for female malignant germ cell tumors","volume":"107","author":"Smith HO","year":"2006","journal-title":"Obstet. Gynecol."},{"key":"e_1_2_10_3_1","volume-title":"WHO classification of Tumours: Female genital Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1002\/1097-0142(197605)37:5<2359::AID-CNCR2820370528>3.0.CO;2-Q","article-title":"Immature (malignant) teratoma of the ovary: A clinical and pathologic study of 58 cases","volume":"37","author":"Norris HJ","year":"1976","journal-title":"Cancer"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1330481","article-title":"Outcome of patients with stage I immature teratoma after surveillance or adjuvant chemotherapy","volume":"14","author":"Marino G","year":"2024","journal-title":"Front. Oncol."},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1097\/PAS.0b013e318198177d","article-title":"SALL4 is a novel sensitive and specific marker of ovarian primitive germ cell tumors and is particularly useful in distinguishing yolk sac tumor from clear cell carcinoma","volume":"33","author":"Cao D","year":"2009","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/PAS.0b013e31812f6ba6","article-title":"Sox2 expression in brain tumors: A reflection of the neuroglial differentiation pathway","volume":"32","author":"Phi JH","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/modpathol.3800793","article-title":"Expression of Sox2 in mature and immature teratomas of central nervous system","volume":"20","author":"Phi JH","year":"2007","journal-title":"Mod. Pathol."},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007224","article-title":"SOX2 regulates common and specific stem cell features in the CNS and endoderm derived organs","volume":"14","author":"Hagey DW","year":"2018","journal-title":"PLoS Genet."},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000082134","article-title":"SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult","volume":"26","author":"Ellis P","year":"2004","journal-title":"Dev. Neurosci."},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2022.154044","article-title":"SOX2 and PRAME in the \u201creprogramming\u201d of seminoma cells","volume":"237","author":"Orsatti A","year":"2022","journal-title":"Pathol. Res. Pract."},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/PAS.0000000000002241","article-title":"Primitive embryonic\u2010type Neuroectodermal\/glandular complexes in testicular germ cell tumors: A mimic of embryonic\u2010type Neuroectodermal tumor","volume":"48","author":"Whaley RD","year":"2024","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00428-024-03911-8","article-title":"Characterization of testicular embryonic\u2010type neuroectodermal tumor and embryonic\u2010type neuroectodermal tissue admixed with mature neuro\u2010glial tissue using a broad immunohistochemical panel","volume":"487","author":"Sciascio L","year":"2025","journal-title":"Virchows Arch."},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00004347-198709000-00002","article-title":"Relation of ovarian dermoid cysts and immature teratomas: An analysis of 350 cases of immature teratoma and 10 cases of dermoid cyst with microscopic foci of immature tissue","volume":"6","author":"Yanai\u2010Inbar I","year":"1987","journal-title":"Int. J. Gynecol. Pathol."},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ncb1481","article-title":"Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1","volume":"8","author":"Zhang J","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"24090","DOI":"10.1074\/jbc.C600122200","article-title":"Sall4 interacts with Nanog and co\u2010occupies Nanog genomic sites in embryonic stem cells","volume":"281","author":"Wu Q","year":"2006","journal-title":"J. Biol. Chem."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70264","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70264","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T23:40:38Z","timestamp":1787355638000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":15,"alternative-id":["10.1111\/his.70264"],"URL":"https:\/\/doi.org\/10.1111\/his.70264","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"his.70264"}}