{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:15:23Z","timestamp":1784232923963,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Clear cell adenocarcinoma of the uterine cervix (CCAC) or vagina (CCAV) is rare and usually presents in postmenopausal women. Paediatric cases are rare, and have historically been associated with intrauterine exposure to diethylstilbestrol (DES). We aimed to summarise outcomes of CCAC and CCAV in children with no history of DES exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Systematic review of the Pubmed\/Medline\/Ovid databases from inception to 2024 according to PRISMA guidelines. The initial search identified 127 articles, and 29 articles were included in the final analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p>Forty\u2010three cases of paediatric CCAC and CCAV were described. Median age at presentation was 10\u00a0years [interquartile range (IQR): 8\u201314\u00a0years]. Most patients presented with stage I tumours and symptoms of prolonged vaginal bleeding. Staging assessment included CT or MRI abdomen\/pelvis and vaginoscopy with biopsy in most cases. Treatments consisted of variable combinations of chemotherapy, radiotherapy (external beam or brachytherapy) and surgery. Surgical procedures included localised resection only, radical trachelectomy or radical hysterectomy with pelvic lymph node clearance. Follow\u2010up information was available for 88% patients and was overall very heterogeneous. Median duration of follow\u2010up was 24\u00a0months [IQR: 14\u201382.5]. There were seven reported deaths, and two additional patients experienced recurrence during follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first systematic review on the management and outcomes of children with CCAC and CCAV. The cases identified were few and heterogeneous, with limited information on longer term outcomes. Current evidence does not allow for the generation of paediatric\u2010specific treatment guidelines. A cautious approach to the management of this rare and aggressive disease is essential, carefully balancing the desire of fertility preservation with the need for cure from disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31786","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:15:43Z","timestamp":1747268143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clear Cell Adenocarcinoma of the Uterine Cervix and Vagina in Children Without Exposure to Diethylstilbestrol"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-2435","authenticated-orcid":false,"given":"Sarah","family":"Braungart","sequence":"first","affiliation":[{"name":"Department of Paediatric Surgery Royal Hospital for Children Glasgow  Glasgow UK"},{"name":"School of Medicine University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Davenport","sequence":"additional","affiliation":[{"name":"Department of Paediatric Surgery Royal Hospital for Children Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.02.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1999.5700"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198702263160905"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19970601)79:11<2229::AID-CNCR22>3.0.CO;2-X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197104222841604"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2020.08.020"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-828X.1965.tb00329.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.13865"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.13867"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgo.2007.11.004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00132"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2011.05.003"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brachy.2022.06.004"},{"issue":"1","key":"e_1_2_10_16_1","first-page":"82","article-title":"Diethylstilbestrol Exposure During Pregnancy With Primary Clear Cell Carcinoma of the Cervix in an 8\u2010Year\u2010Old Granddaughter: A Multigenerational Effect of Endocrine Disruptors?","volume":"36","author":"Gaspari L.","year":"2021","journal-title":"Human Reproduction"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2010.05.032"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2004.12.050"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e3182011236"},{"issue":"5","key":"e_1_2_10_20_1","first-page":"549","article-title":"Adenocarcinoma de C\u00e9lulas Claras de Cervix en Nina no Expuesta a Dietiletilbestrol [Clear Cell Cervical Adenocarcinoma in a Girl Not Exposed to Diethylstillbestrol]","volume":"50","author":"Romero\u2010Dur\u00e1n E.","year":"2012","journal-title":"Revista M\u00e9dica del Instituto Mexicano del Seguro Social"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2023.101135"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000018646"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10024-005-0047-2"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950210912"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(76)90158-7"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/gyn.1997.13.31"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2016-218730"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.11622\/smedj.2016138"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e318290cb1b"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-008-0781-3"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3348\/jksr.2013.69.4.321"},{"issue":"1","key":"e_1_2_10_32_1","first-page":"38","article-title":"Adenocarcinoma de C\u00e9lulas Claras de C\u00e9rvix en Ni\u00f1a de 12 A\u00f1os sin Exposici\u00f3n Previa a dietilestilbestrol: Reporte de casoia [Clear Cell Adenocarcinoma of the Cervix in a 12\u2010Year Old Girl Without Previous Exposure to Diethylstilbestrol: A Case Report]","volume":"21","author":"Morrugares\u2010Ixtepan M. 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