{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:15:08Z","timestamp":1789708508005,"version":"4.0.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Differences\/disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>The aim of this study is to report the histological characteristics and immunoexpression patterns of gonadal parenchyma in patients with 46,XX testicular and ovotesticular DSD, with a focus on the detection of germ cell malignancies.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Inclusion criteria were <jats:italic>SRY-<\/jats:italic>negative 46,XX testicular and ovotesticular DSD with available samples from gonadal biopsy or gonadectomy for the review of histological findings. Gonadal histology was assessed on hematoxylin and eosin-stained sections and immunohistochemical analysis. Histopathological criteria from the last World Health Organization classification of urogenital tumors were used to identify undifferentiated gonadal tissue, gonadoblastoma, and dysgerminoma.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Median age at first histological evaluation of gonadal samples was 1.46 years (range: 0.16\u201316 years). Totally 15 patients were classified as ovotesticular and only 1 as testicular DSD. Most individuals had bilateral ovotestes (12\/15). No histological alterations were found in the ovarian parenchyma, while signs of dysgenesis were seen in all cases of testicular parenchyma. In 4\/15 ovotesticular DSD, a prepubertal biopsy failed to identify ovarian parenchyma. We detected early prepubertal preinvasive and invasive malignancies in this cohort (five patients had undifferentiated gonadal tissue, five gonadoblastoma, and one dysgerminoma).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>46,XX disorders of gonadal development are historically considered at a low risk for germ cell cancer, and the need for assessment of gonadal histology has been questioned. The finding of early germ cell malignancies in our cohort brings awareness and needs further research.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-22-0283","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T11:06:27Z","timestamp":1657883187000},"page":"451-462","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":18,"title":["Gonadal tumor development in 46,XX disorders of gonadal development"],"prefix":"10.1093","volume":"187","author":[{"given":"Mariana","family":"Costanzo","sequence":"first","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Sol","family":"Touzon","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Marino","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Guercio","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Celeste","family":"Mattone","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"P\u00e9rez Garrido","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Marcela","family":"Bailez","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vaiani","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Laura","family":"Galluzzo Mutti","sequence":"additional","affiliation":[{"name":"Servicio de Patolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Belgorosky","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-6180","authenticated-orcid":true,"given":"Esperanza","family":"Berensztein","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Pediatr\u00eda \u2018Prof. Dr. Juan Pedro Garrahan\u2019, Buenos Aires, Argentina"},{"name":"2da. 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