{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T18:13:26Z","timestamp":1783188806942,"version":"3.54.6"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ovotesticular disorders of sex development (DSD) are variations in sex development characterized by the presence of both ovarian and testicular parenchyma in the same individual, with histopathologic confirmation being mandatory for accurate diagnosis. FOXL2, a transcription factor involved in ovarian differentiation and maintenance, has emerged as a potential immunohistochemical marker for ovarian tissue. However, its diagnostic utility in pediatric DSD patients, particularly in identifying ovotesticular cords (OVTCs), remains underexplored. This study aims to evaluate the immunohistochemical expression of FOXL2 in gonadal tissues of patients with ovotesticular DSD and gonadal dysgenesis to determine its value in identifying ovotesticular cords (OVTCs) and support the diagnosis of ovotestis. A retrospective histopathological analysis was conducted on 19 gonadal specimens from 14 pediatric patients diagnosed with ovotesticular DSD or gonadal dysgenesis. Cases were retrieved from the surgical pathology archives of the University of Pittsburgh Medical Center \u2013 Children\u2019s Hospital of Pittsburgh and the consultation files of Miguel Reyes-M\u00fagica. Formalin-fixed, paraffin-embedded tissue sections underwent hematoxylin and eosin staining and immunohistochemical analysis for FOXL2 and additional gonadal markers. FOXL2 expression was assessed for nuclear localization, and distribution within stromal and cordal compartments, with staining intensity semi-quantitatively scored as 0 (no positive cells), 1+ (few-to-moderate, &lt;\u200950%), or 2+ (numerous, \u2265\u200950%). Among the 19 gonads examined, histologic diagnoses included 4 ovaries, 11 ovotestes (among which 3 were classified as bipolar ovotestis, 2 as streak-type ovotestis), and 4 dysgenetic testes, and streak gonads. FOXL2 showed strong and diffuse nuclear expression in ovarian stroma and was consistently positive in ovotestes, including focal intracordal staining within OVTCs, even in gonads with predominantly testicular histology. Of the 12 gonads with ovotesticular DSD (including 11 ovotestes and 1 ovary with OVTCs), 11 (92%) demonstrated FOXL2 expression in testicular components. All gonads classified as ovaries were FOXL2-positive, while dysgenetic testes lacking histologic evidence of ovarian differentiation were either negative or showed only rare positive stromal cells without intracordal expression. FOXL2 staining correlated with histologic and clinical findings, confirming its value in identifying ovarian differentiation and supporting the diagnosis of ovotesticular DSD. FOXL2 immunohistochemistry is a reliable marker of ovarian differentiation and can aid in the diagnosis of ovotesticular DSD. Its expression in ovarian stroma and OVTCs enhances the histological evaluation of ambiguous gonads and supports its routine use in the diagnostic workup of pediatric DSD patients.<\/jats:p>","DOI":"10.1007\/s00428-026-04591-2","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:30:08Z","timestamp":1779409808000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["FOXL2 expression in dysgenetic gonads supports the diagnostic possibility of ovotesticular differences of sex development"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-2595","authenticated-orcid":false,"given":"Hisham F.","family":"Bahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9224-4920","authenticated-orcid":false,"given":"Catherine K.","family":"Gestrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-1296","authenticated-orcid":false,"given":"Claudia M.","family":"Salgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence S.","family":"Baskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-3702","authenticated-orcid":false,"given":"Miguel","family":"Reyes-M\u00fagica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"4591_CR1","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1097\/PAS.0b013e31820a406c","volume":"35","author":"OM Al-Agha","year":"2011","unstructured":"Al-Agha OM, Huwait HF, Chow C, Yang W, Senz J, Kalloger SE, Huntsman DG, Young RH, Gilks CB (2011) FOXL2 is a sensitive and specific marker for sex cord-stromal tumors of the ovary. 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