Gonadoblastoma with Dysgerminoma in a Phenotypically Turner-Like Girl with 45,X/46,XY Karyotype

Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X[97,3]/46,XY[2,7] and 45,X[92,7]/46,XY[4,5]/47,XYY [2,8] mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor.


Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers. Endocr Rev 2006;27:468-484. Epub 2006 May 30

Looijenga LH, Hersmus R, de Leeuw BH, Stoop H, Cools M, Oosterhuis JW, Drop SL, Wolffenbuttel KP. Gonadal tumours and DSD. Best Pract Res Clin Endocrinol Metab 2010;24:291-310.

Simpson JL. Abnormal sexual differentiation in humans. Annu Rev Genet 1982;16:193-224.

Farrugia MK, Sebire NJ, Achermann JC, Eisawi A, Duffy PG, Mushtaq I. Clinical and gonadal features and early surgical management of 45,X/46,XY and 45,X/47,XYY chromosomal mosaicism presenting with genital anomalies. J Pediatr Urol 2013;9:139-144. Epub 2012 Jan 26

Cools M, Pleskacova J, Stoop H, Hoebeke P, Van Laecke E, Drop SL, Lebl J, Oosterhuis JW, Looijenga LH, Wolffenbuttel KP; Mosaicism Collaborative Group. Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism. J Clin Endocrinol Metab 2011;96:1171-1180. Epub 2011 Apr 20

Chang HJ, Clark RD, Bachman H. The phenotype of 45,X/ 46,XY mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet 1990;46:156-167.

Rosenberg C, Frota-Pessoa O, Vianna-Morgante AM, Chu TU. Phenotypic spectrum of 45, X/46, XY individuals. Am J Med Genet 1987;27:553-559.

Telvi L, Lebbar A, Del Pino O, Barbet JP, Chaussain JL. 45,X/ 46,XY mosaicism: report of 27 cases. Pediatrics 1999;104:304-308.

Tosson H, Rose SR. Gartner LA. Description of children with 45,X/46,XY karyotype. Eur J Pediatr 2012;171:521-529. Epub 2011 Oct 14

Cools M. Germ cell cancer risk in DSD patients. Ann Endocrinol (Paris) 2014;75:67-71. Epub 2014 Apr 29

Page DC. Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development 1987;101(Suppl)151-155.

Li Y, Tabatabai ZL, Lee TL, Hatakeyama S, Ohyama C, Chan WY, Looijenga LH, Lau YF. The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors. Hum Pathol 2007;38:1470- 1481. Epub 2007 May 22

Hersmus R, de Leeuw BH, Stoop H, Bernard P, van Doorn HC, Brüggenwirth HT, Drop SL, Oosterhuis JW, Harley VR, Looijenga LH. A novel SRY missense mutation affecting nuclear import in a 46,XY female patient with bilateral gonadoblastoma. Eur J Hum Genet 2009;17:1642-1649. Epub 2009 Jun 10

Bianco B, Lipay M, Guedes A, Oliveira K, Verreschi IT. SRY gene increases the risk of developing gonadoblastoma and/ or nontumoral gonadal lesions inTurner syndrome. Int J Gynecol Pathol 2009;28:197-202.

Patsalis PC, Skordis N, Sismani C, Kousoulidou L, Koumbaris G, Eftychi C, Stavrides G, Ioulianos A, Kitsiou-Tzeli S, Galla-Voumvouraki A, Kosmaidou Z, Hadjiathanasiou CG, McElreavey K. Identification of high frequency of Y chromosome deletions in patients with sex chromosome mosaicism and correlation with the clinical phenotype and Y-chromosome instability. Am J Med Genet A 2005;135:145- 149.

Siffroi JP, Le Bourhis C, Krausz C, Barbaux S, Quintana-Murci L, Kanafani S, Rouba H, Bujan L, Bourrouillou G,Seifer I, Boucher D, Fellous M, McElreavey K, Dadoune JP. Sex chromosome mosaicism in males carrying Y chromosome long arm deletions. Hum Reprod 2000;15:2559-2562.

Alvarez-Nava F, Puerta H, Soto M, Pineda L, Temponi A. High incidence of Y-chromosome microdeletions in gonadal tissues from patients with 45,X/46,XY gonadal dysgenesis. Fertil Steril 2008;89:458-60. Epub 2007 May 25

Bianchi NO, Richard SM, Peltomaki P, Bianchi MS. Mosaic AZF deletions and susceptibility to testicular tumors. Mutat Res 2002;503:51-62.

Nishi MY, Costa EM, Oliveira SB, Mendonca BB, Domenice S. The role of SRY mutations in the etiology of gonadal dysgenesis in patients with 45,X/46,XY disorder of sex development and variants. Horm Res Paediatr 2011;75:26- 31. Epub 2010 Aug 12

Changchien YC, Haltrich I, Micsik T, Kiss E, Fonyad L, Papp G, Sapi Z. Gonadoblastoma: Case report of two young patients with isochromosome 12p found in the dysgerminoma overgrowth component in one case. Pathol Res Pract 2012;208:628-632. Epub 2012 Aug 18

Pena-Alonso R, Nieto K, Alvarez R, Palma I, Najera N, Eraña L, Dorantes LM, Kofman-Alfaro S, Queipo G. Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants. Mod Pathol 2005;18:439-445.

Kaynak Göster