{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:18:22Z","timestamp":1788995902724,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T00:00:00Z","timestamp":1421625600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"CONICET, National Research Council of Argentina","award":["PIP 5479"],"award-info":[{"award-number":["PIP 5479"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Summary<\/jats:title>All malignant testicular germ cell tumors (TGCT<\/jats:styled-content>) of adult men are preceded by an in situ stage (CIS<\/jats:styled-content>) of protracted evolution. The adult CIS<\/jats:styled-content> is well characterized, but there is debate on the phenotype of infantile CIS<\/jats:styled-content>, its distinction from delayed maturation of germ cells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD<\/jats:styled-content>) and dysgenetic testes (90% ranging from neonates to 12\u00a0years, mean age 4.7\u00a0years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities\/atypia (GCA<\/jats:styled-content>), expression of OCT<\/jats:styled-content> 3\/4 (a pluripotency\u2010undifferentiation marker), germ cell ploidy and evolution to CIS<\/jats:styled-content> and invasive TGCT<\/jats:styled-content>. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients: bilateral testes (BT<\/jats:styled-content>\u2010DSD<\/jats:styled-content>, n\u00a0<\/jats:italic>=\u00a021), one testis and one streak gonad (CT<\/jats:styled-content>\u2010DSD<\/jats:styled-content>, C for combined, n\u00a0<\/jats:italic>=\u00a013), and ovarian\u2010testicular combinations (OT<\/jats:styled-content>\u2010DSD<\/jats:styled-content>, n\u00a0<\/jats:italic>=\u00a09). There were 5 boys with infantile CIS<\/jats:styled-content>, bilateral in 3 (total of 8 infantile CIS<\/jats:styled-content>) and two patients with adult CIS<\/jats:styled-content>, bilateral in one (total of 3 adult CIS<\/jats:styled-content>). Two patients had bilateral seminomas one at 12\u201317 and the other at 23\u00a0years. Histological dysgenesis was significantly higher in CT<\/jats:styled-content>\u2010DSD<\/jats:styled-content> (p\u00a0<\/jats:italic><\u00a00.05), that had only 1 CIS<\/jats:styled-content>. The highest frequency of GCA<\/jats:styled-content> was in BT<\/jats:styled-content>\u2010DSD<\/jats:styled-content> (p<\/jats:italic>\u00a0<\u00a00.05), which coincided with a total of 11CIS\u00a0+\u00a0Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy (p<\/jats:italic>\u00a0<\u00a00.02), and GCA<\/jats:styled-content> were more frequent in aneuploid than in diploid samples (p<\/jats:italic>\u00a0<\u00a00.02). All CIS<\/jats:styled-content> and TGCT<\/jats:styled-content> were OCT<\/jats:styled-content> 3\/4 positive. Finally, there was a significant association between the triad Aneuploidy\u00a0+\u00a0GCA<\/jats:styled-content>\u00a0+\u00a0OCT<\/jats:styled-content> 3\/4 positivity and the incidence of CIS<\/jats:styled-content> (Fisher Exact test p<\/jats:italic>\u00a0<\u00a00.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetal testicular cords) is inversely related to the incidence of CIS<\/jats:styled-content>. Our data demonstrate that the combined use of OCT<\/jats:styled-content> 3\/4 expression, quantification of germ cell abnormalities\u2010atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS<\/jats:styled-content> with high risk of malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.<\/jats:p>","DOI":"10.1111\/andr.301","type":"journal-article","created":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T10:21:56Z","timestamp":1421662916000},"page":"59-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy"],"prefix":"10.1111","volume":"3","author":[{"given":"H. E.","family":"Chemes","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1 (CEDIE) CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Venara","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1 (CEDIE) CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"del Rey","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1 (CEDIE) CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J.","family":"Arcari","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Endocrinolog\u00eda Hospital de Ni\u00f1os \u201cDr. Ricardo Guti\u00e9rrez\u201d Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. P.","family":"Musse","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1 (CEDIE) CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Papazian","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Hospital Nacional \u201cProf. Dr. Alejandro Posadas\u201d Haedo Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Forclaz","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Hospital Nacional \u201cProf. Dr. Alejandro Posadas\u201d Haedo Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1 (CEDIE) CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2011.01192.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000104772"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(87)90509-7"},{"key":"e_1_2_7_5_1","first-page":"493","article-title":"Gonadal histology in patients with male pseudohermaphroditism and atypical gonadal dysgenesis: relation to theories of sex differentiation","volume":"40","author":"Bergad\u00e1 C","year":"1962","journal-title":"Acta Endocrinol (Copenh)"},{"key":"e_1_2_7_6_1","first-page":"291","volume-title":"Intersexual States. 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