{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:18:19Z","timestamp":1788995899825,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Tuebingen","award":["open access fund"],"award-info":[{"award-number":["open access fund"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The risk of gonadal germ cell tumors is increased over the lifetime of patients with XY-disorders of sex development (XY-DSD). The aim of this study was to evaluate clinical features and histopathological outcome after gonadectomy in patients with XY-DSD to assess the risk of malignant transformation to gonadal germ cell tumors. Thirty-five women treated for XY-DSD at our hospital between 2003 and 2020 were enrolled in this study. Twenty-seven (77%) underwent prophylactic gonadectomy, 10 (29%) at our department and 17 (48%) at external hospitals. Eight (23%) patients didn\u2019t receive gonadectomy. Of the patients who underwent a surgical procedure at our hospital, two patients were diagnosed with a unilateral seminoma, one patient with a bilateral and one patient with a unilateral Sertoli cell adenoma. According to these findings, preventive gonadectomy in patients with XY-DSD should be taken into consideration. Guidelines concerning the necessity of gonadectomy to avoid malignant transformation are still lacking. The risk of malignant germ cell tumors from rudimentary gonads has not been investigated sufficiently to date, as it is mostly based on case series due to the rarity of the condition. In our study we retrospectively analyzed patients who partly underwent bilateral gonadectomy, aiming to fill this gap. Concerning the ideal point of time for gonadectomy, further studies with a higher number of patients are needed.<\/jats:p>","DOI":"10.3390\/ijerph18115648","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T13:14:21Z","timestamp":1621948461000},"page":"5648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Malignant Germ Cell Tumors and Their Precursor Gonadal Lesions in Patients with XY-DSD: A Case Series and Review of the Literature"],"prefix":"10.3390","volume":"18","author":[{"given":"Sahra","family":"Steinmacher","sequence":"first","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University Hospital, Calwerstr. 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-1542","authenticated-orcid":false,"given":"Sara Y.","family":"Brucker","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University Hospital, Calwerstr. 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrina","family":"K\u00f6lle","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University Hospital, Calwerstr. 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8628-6745","authenticated-orcid":false,"given":"Bernhard","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University Hospital, Calwerstr. 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Sch\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University Hospital, Calwerstr. 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Rall","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University Hospital, Calwerstr. 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/adc.2006.098319","article-title":"Consensus Statement on Management of Intersex Disorders","volume":"91","author":"Hughes","year":"2005","journal-title":"Arch. Dis. Child."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.beem.2007.11.001","article-title":"Disorders of Sex Development: A New Definition and Classification","volume":"22","author":"Hughes","year":"2008","journal-title":"Best Pr. Res. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jpurol.2006.03.004","article-title":"Consensus Statement on Management of Intersex Disorders","volume":"2","author":"Hughes","year":"2006","journal-title":"J. Pediatr. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000442975","article-title":"Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care","volume":"85","author":"Lee","year":"2016","journal-title":"Horm. Res. Paediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1515\/jpem-2014-0522","article-title":"Gonadal Malignancy Risk and Prophylactic Gonadectomy in Disorders of Sexual Development","volume":"28","author":"Abaci","year":"2015","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1136\/bmj.308.6935.1041","article-title":"Anonymous Gender Identity in Testicular Feminisation Phenotypically, Anatomically, Legally, and Socially Female","volume":"308","author":"Ahlquist","year":"1994","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/09513590.2012.705378","article-title":"Androgen Insensitivity Syndrome","volume":"29","author":"Mendoza","year":"2012","journal-title":"Gynecol. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0165-4608(87)90180-4","article-title":"Abnormal Sexual Differentiation and Neoplasia","volume":"25","author":"Verp","year":"1987","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.21037\/tau-19-726","article-title":"Gonadal Malignancy in Patients with Differences of Sex Development","volume":"9","author":"Morin","year":"2020","journal-title":"Transl. Androl. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1159\/000314536","article-title":"Tumor Risk in Disorders of Sex Development","volume":"4","author":"Pleskacova","year":"2010","journal-title":"Sex. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/path.2378","article-title":"Stem Cell Factor as a Novel Diagnostic Marker for Early Malignant Germ Cells","volume":"216","author":"Stoop","year":"2008","journal-title":"J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.beem.2007.05.001","article-title":"Tumor Risk in Disorders of Sex Development (DSD)","volume":"21","author":"Looijenga","year":"2007","journal-title":"Best Pr. Res. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1210\/er.2006-0005","article-title":"Germ Cell Tumors in the Intersex Gonad: Old Paths, New Directions, Moving Frontiers","volume":"27","author":"Cools","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/S0140-6736(12)60071-3","article-title":"Androgen Insensitivity Syndrome","volume":"380","author":"Hughes","year":"2012","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000478082","article-title":"Gonadectomy in Complete Androgen Insensitivity Syndrome: Why and When?","volume":"11","author":"Hiort","year":"2017","journal-title":"Sex. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4103\/0973-1482.73337","article-title":"Pure Seminoma in the Setting of Androgen Insensitivity Syndrome Treated with Surgical Resection and Para-aortic Radiation: A Case Report and Review of Literature","volume":"6","author":"Parashar","year":"2010","journal-title":"J. Cancer Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1687-9856-2014-4","article-title":"State of the Art Review in Gonadal Dysgenesis: Challenges in Diagnosis and Management","volume":"2014","author":"Mansouri","year":"2014","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1111\/j.1365-2265.2012.04330.x","article-title":"Timing of Gonadectomy in Adult Women with Complete Androgen Insensitivity Syndrome (CAIS): Patient Preferences and Clinical Evidence","volume":"76","author":"Deans","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1148\/radiol.13121068","article-title":"Evaluation of Retained Testes in Adolescent Girls and Women with Complete Androgen Insensitivity Syndrome","volume":"268","author":"Nakhal","year":"2013","journal-title":"Radiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000363642","article-title":"Managing the Risk of Germ Cell Tumourigenesis in Disorders of Sex Development Patients","volume":"27","author":"Cools","year":"2014","journal-title":"Endocr. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.juro.2008.06.045","article-title":"Long-Term Followup and Comparison Between Genotype and Phenotype in 29 Cases of Complete Androgen Insensitivity Syndrome","volume":"180","author":"Cheikhelard","year":"2008","journal-title":"J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1210\/jc.2009-2146","article-title":"Novel (60%) and Recurrent (40%) Androgen Receptor Gene Mutations in a Series of 59 Patients with a 46, XY Disorder of Sex Development","volume":"95","author":"Audi","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/cen.13255","article-title":"Gonadal Tumour Risk in 292 Phenotypic Female Patients with Disorders of Sex Development Containing Y Chromosome or Y-derived Sequence","volume":"86","author":"Huang","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.fertnstert.2007.08.070","article-title":"Neovagina Creation in Vaginal Agenesis: Development of a New Laparoscopic Vecchietti-based Procedure and Optimized Instruments in a Prospective Comparative Interventional Study in 101 Patients","volume":"90","author":"Brucker","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jpag.2014.02.002","article-title":"Laparoscopically Assisted Neovaginoplasty in Vaginal Agenesis: A Long-Term Outcome Study in 240 Patients","volume":"27","author":"Rall","year":"2014","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/path.1890","article-title":"Testicular Development in the Complete Androgen Insensitivity Syndrome","volume":"208","author":"Hannema","year":"2006","journal-title":"J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1210\/jc.2005-2554","article-title":"Gonadoblastoma Arising in Undifferentiated Gonadal Tissue within Dysgenetic Gonads","volume":"91","author":"Cools","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"445","DOI":"10.2350\/11-01-0960-OA.1","article-title":"Undifferentiated Gonadal Tissue, Y Chromosome Instability, and Tumors in XY Gonadal Dysgenesis","volume":"14","author":"Lemieux","year":"2011","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_29","first-page":"E958","article-title":"Patients with Disorders of Sex Development (DSD) at Risk of Gonadal Tumour Development: Management Based on Laparoscopic Biopsy and Molecular Diagnosis","volume":"110","author":"Holterhus","year":"2012","journal-title":"BJU Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"218","DOI":"10.5603\/FHC.a2015.0021","article-title":"The Risk of Neoplasm Associated with Dysgenetic Testes in Prepubertal and Pubertal\/Adult Patients","volume":"53","author":"Wolski","year":"2015","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/humrep\/deu109","article-title":"Increased Risk of Gonadal Malignancy and Prophylactic Gonadectomy: A Study of 102 Phenotypic Female Patients with Y Chromosome or Y-derived Sequences","volume":"29","author":"Liu","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1159\/000091592","article-title":"Puberty in Subjects with Complete Androgen Insensitivity Syndrome","volume":"65","author":"Papadimitriou","year":"2006","journal-title":"Horm. Res. Paediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/01.mop.0000193316.60580.d7","article-title":"Intersex Genetic Anomalies with Malignant Potential","volume":"18","author":"Fallat","year":"2006","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1006\/gyno.2001.6535","article-title":"Simultaneous Sertoli Cell Tumor and Adenocarcinoma of the Tunica Vaginalis Testis in a Patient with Testicular Feminization","volume":"84","author":"Fleckenstein","year":"2002","journal-title":"Gynecol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.semcdb.2015.09.013","article-title":"Pathogenesis of Germ Cell Neoplasia in Testicular Dysgenesis and Disorders of Sex Development","volume":"45","author":"Johansen","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.1210\/jc.2005-0139","article-title":"Morphological and Immunohistochemical Differences between Gonadal Maturation Delay and Early Germ Cell Neoplasia in Patients with Undervirilization Syndromes","volume":"90","author":"Cools","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000477921","article-title":"Update on the Pathophysiology and Risk Factors for the Development of Malignant Testicular Germ Cell Tumors in Complete Androgen Insensitivity Syndrome","volume":"11","author":"Cools","year":"2017","journal-title":"Sex. Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.jpag.2015.03.011","article-title":"Timing of Gonadectomy in Patients with Complete Androgen Insensitivity Syndrome\u2013Current Recommendations and Future Directions","volume":"29","author":"Patel","year":"2016","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-0-387-69116-9_2","article-title":"A Genetic Screen Implicates miRNA-372 and miRNA-373 as Oncogenes in Testicular Germ Cell Tumors","volume":"604","author":"Voorhoeve","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1365-2605.2007.00765.x","article-title":"Relevance of microRNAs in Normal and Malignant Development, Including Human Testicular Germ Cell Tumours","volume":"30","author":"Looijenga","year":"2007","journal-title":"Int. J. Androl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrurol.2012.86","article-title":"Testicular Cancer: A New Generation of Biomarkers for Malignant Germ Cell Tumours","volume":"9","author":"Murray","year":"2012","journal-title":"Nat. Rev. Urol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/ng.2634","article-title":"Meta-analysis Identifies Four New Loci Associated with Testicular Germ Cell Tumor","volume":"45","author":"Chung","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1111\/j.1365-2605.2011.01156.x","article-title":"A Stratified Genetic Risk Assessment for Testicular Cancer","volume":"34","author":"Kratz","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1056\/NEJMra022784","article-title":"Sex Determination and Differentiation","volume":"350","author":"MacLaughlin","year":"2004","journal-title":"New Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lanciotti, L., Cofini, M., Leonardi, A., Bertozzi, M., Penta, L., and Esposito, S. (2019). Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS). Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16071268"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrendo.2014.130","article-title":"DSDs: Genetics, Underlying Pathologies and Psychosexual Differentiation","volume":"10","author":"Arboleda","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/cen.12857","article-title":"Society for Endocrinology UK Guidance on the Initial Evaluation of an Infant or an Adolescent with a Suspected Disorder of Sex Development (Revised 2015)","volume":"84","author":"Ahmed","year":"2016","journal-title":"Clin. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nrendo.2014.108","article-title":"Management of Disorders of Sex Development","volume":"10","author":"Hiort","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S2213-8587(18)30197-9","article-title":"Oestrogen vs. Androgen in Hormone-replacement Therapy for Complete Androgen Insensitivity Syndrome: A Multicentre, Randomised, Double-dummy, Double-blind Crossover Trial","volume":"6","author":"Birnbaum","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1148\/rg.275065172","article-title":"US\u2013MR Imaging Correlation in Pathologic Conditions of the Scrotum","volume":"27","author":"Kim","year":"2007","journal-title":"Radiographics"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/11\/5648\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:07:32Z","timestamp":1760162852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/11\/5648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,25]]},"references-count":50,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijerph18115648"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18115648","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,25]]}}}