46, XY pure gonadal dysgenesis with malignant mixed germ cell tumor: a case report and literature review

46, XY pure gonadal dysgenesis, which is also known as Swyer syndrome, is a medical condition of gonadal abnormalities. The authors report a case of a 15-year-old phenotypic female who presented with bulky abdominal mass and underwent laparotomy with right cystectomy, as well as left ovary biopsy. Post-operational pathology demonstrated that malignant mixed germ cell tumors in the right ovary. Taking consideration of no menstruation, abnormal hormone levels, and malignant mixed germ cell tumors in the ovary, the patient took the karyotype test and the result was confirmed: 46, XY. Taking into consideration pure gonadal dysgenesis with mixed malignant germ cell tumors, surgical resection of bilateral gonads is primarily recommended. The patient and her families were well consented on sex selection, cancer treatment strategy, reproductive function, and resection of the pelvic mass, together with uterus, it was decided to maintain female phenotype without reproductive function. Post-operational pathology showed ovarian gonadal blastoma and dysgerminoma, with bilateral calcification. The nodule from the excavatio rectouterina was identified as mature teratoma, without immature components. The patient received four cycles of postoperative chemotherapy using bleomycin, etoposide, and cisplatin (BEP) regime. Long-term hormone replacement therapy was recommended. There has been no sign of recurrence since then.

46, XY pure gonadal dysgenesis; Malignant mixed germ cell tumor; Immature teratoma; Yolk sac tumor; Gonadal blastoma

[1] Sinclair A.H., Berta P., Palmer M.S., Hawkins J.R., Griffiths B.L., Smith M.J., et al.: “A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif”. Nature, 1990, 346, 240.

[2] Hawkins J.R.: “Cloning and mutational analysis of SRY”. Horm Res., 1992, 38, 222.

[3] Ságodi L., Ladányi E., Kiss Á., Tar A., Lukács V., Minik K., Vámosi I.: “Pure 46,XY gonadal dysgenesis”. Orv. Hetil., 2010, 151, 1991. [In Hungarian]

[4] Hawkins J.R., Taylor A., Goodfellow P.N., Migeon C.J., Smith K.D., Berkovitz G.D.: “Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis”. Am. J. Hum. Genet., 1992, 51, 979.

[5] Lim H.N., Freestone S.H., Romero D., Kwok C., Hughes I.A., Hawkins J.R.: “Candidate genes in complete and partial XY sex reversal: mutation analysis of SRY, SRY-related genes and FTZ-F1”. Mol. Cell Endocrinol., 1998, 140, 51.

[6] Jorgensen P.B., Kjartansdottir K.R., Fedder J.: “Care of women with XY karyotype: a clinical practice guideline”. Fertil Steril., 2010, 94, 105.

[7] Hamin J.N., Arkoncel F.R., Lantion-Ang F.L., Sandoval M.A.: “46 XY gonadal dysgenesis in adulthood ‘pitfalls of late diagnosis’”. BMJ Case Rep., 2012, 2012, pii: bcr1220103626.

[8] Agarwal A., Agarwal S.: “Swyer Syndrome with gonadoblastoma: a clinicoradiological approach”. J. Hum. Reprod. Sci., 2017, 10, 65.

[9] Yadav P., Khaladkar S., Gujrati A.: “Imaging Findings in Dysgerminoma in a Case of 46 XY, Complete Gonadal Dysgenesis (Swyer syndrome)”. J. Clin. Diagn. Res., 2016, 10, TD10.

[10] Karimian N., Ghadakzadeh S., Eshraghi M.: “Swyer syndrome in a woman with pure 46,XY gonadal dysgenesis and a hypoplastic uterus: a rare presentation”. Fertil. Steril., 2010, 93, 267.e13.

[11] Nunes E., Rodrigues C., Geraldes F., Aguas F.: “Differentiating Swyer syndrome and complete androgen insensitivity syndrome: a diagnostic dilemma”. J. Pediatr. Adolesc. Gynecol., 2014, 27, e67.

[12] Zielinska D., Zajaczek S., Rzepka-Gorska I.: “Tumors of dysgenetic gonads in Swyer syndrome”. J. Pediatr. Surg., 2007, 42, 1721.

[13] Manuel M., Katayama P.K., Jones H.W., Jr.: “The age of occurrence of gonadal tumors in intersex patients with a Y chromosome”. Am. J. Obstet. Gynecol., 1976, 124, 293.

[14] Capito C., Leclair M.D., Arnaud A., David A., Baron S., Corradini N., Héloury Y.: “46,XY pure gonadal dysgenesis: clinical presentations and management of the tumor risk”. J. Pediatr. Urol., 2011, 7, 72.

[15] King T.F., Conway G.S.: “Swyer syndrome”. Curr. Opin. Endocrinol. Diabetes Obes., 2014, 21, 504.

[16] Moreira A.I., Silva J.C., Ferreira M.S., Lanhoso A.: “Bilateral dysgerminoma in a patient with a previous diagnosis of Swyer syndrome”. J. Obstet. Gynaecol. Res., 2012, 38, 452.

[17] Jurgensen M., Hiort O., Holterhus P.M., Thyen U.: “Gender role behavior in children with XY karyotype and disorders of sex development”. Horm. Behav., 2007, 51, 443.

[18] Johannsen T.H., Ripa C.P., Mortensen E.L., Main K.M.: “Quality of life in 70 women with disorders of sex development”. Eur J Endocrinol., 2006, 155, 877.

[19] Williams S.D., Blessing J.A., Hatch K.D., Homesley H.D.: “Chemotherapy of advanced dysgerminoma: trials of the Gynecologic Oncology Group”. J. Clin. Oncol., 1991, 9, 1950.

[20] Krum S.A., Miranda-Carboni G.A., Hauschka P.V., Carroll J.S., Lane T.F., Freedman L.P., Brown M.: “Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival”. EMBO J., 2008, 27, 535.

[21] Talerman A., Verp M.S., Senekjian E., Gilewski T., Vogelzang N.: “True hermaphrodite with bilateral ovotestes, bilateral gonadoblastomas and dysgerminomas, 46,XX/46,XY karyotype, and a successful pregnancy”. Cancer, 1990, 66, 2668.

[22] Chen M.J., Yang J.H., Mao T.L., Ho H.N., Yang Y.S.: “Successful pregnancy in a gonadectomized woman with 46,XY gonadal dysgenesis and gonadoblastoma”. Fertil. Steril., 2005, 84, 217.

[23] Selvaraj K., Ganesh V., Selvaraj P.: “Successful pregnancy in a patient with a 46,XY karyotype”. Fertil. Steril., 2002, 78, 419.

[24] Tulic I., Tulic L., Micic J.: “Pregnancy in patient with Swyer syndrome”. Fertil. Steril., 2011, 95,1789.e1.

[25] Creatsas G., Deligeoroglou E., Tsimaris P., Pantos K., Kreatsa M.: “Successful pregnancy in a Swyer syndrome patient with preexisting hypertension”. Fertil. Steril., 2011, 96, e83.