{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:44:23Z","timestamp":1788572663839,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Inflammatory and nested testicular sex cord tumor (IN-TSCT) is a recently characterized malignant neoplasm within the spectrum of testicular sex cord\u2013stromal tumors. Previously misclassified as Sertoli cell tumor, not otherwise specified, or as seminoma, this entity has emerged as a distinct clinicopathologic and molecular subtype defined by recurrent EWSR1::ATF1 gene fusions and a potentially aggressive clinical course. Patients most commonly present with unilateral painless testicular enlargement, and radiologic findings are typically nonspecific. Histologically, tumors demonstrate solid and nested growth patterns, epithelioid cytology with eosinophilic to clear cytoplasm, prominent hyalinized stroma, and a conspicuous inflammatory infiltrate. Immunophenotypically, tumors express sex cord\u2013stromal markers, including steroidogenic factor-1 (SF-1) and inhibin, and frequently co-express epithelial membrane antigen and CD30 while lacking germ cell tumor markers. Molecular studies indicate fusion-driven oncogenesis associated with low tumor mutational burden. Published cases suggest that IN-TSCT may exhibit aggressive clinical behavior, including metastatic spread in a subset of patients; however, the total number of reported cases remains very limited, and the true metastatic risk and prognostic spectrum have not yet been clearly defined. This review synthesizes the available literature to provide a comprehensive clinicopathologic and molecular overview of this emerging tumor entity.<\/jats:p>","DOI":"10.3390\/genes17030340","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammatory and Nested Testicular Sex Cord Tumors: Clinical and Molecular Characterization"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1704-1517","authenticated-orcid":false,"given":"Panagiotis J.","family":"Vlachostergios","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, IASO Thessalias Hospital, 41500 Larissa, Greece"},{"name":"Department of Urology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"},{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foteini","family":"Karasavvidou","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital of Larissa, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-9944","authenticated-orcid":false,"given":"Konstantinos","family":"Evmorfopoulos","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Zachos","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios","family":"Tzortzis","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1097\/PAS.0000000000002022","article-title":"Inflammatory and nested testicular sex cord tumor: A novel neoplasm with aggressive clinical behavior and frequent EWSR1::ATF1 gene fusions","volume":"47","author":"Acosta","year":"2023","journal-title":"Am. 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