Dysgerminoma in a Case of Swyer Syndrome

Journal of Infertility and Reproductive Biology, 2019, Volume 7, Issue 1, Pages: 1-3 Dysgerminoma in a Case of Swyer Syndrome Bishista Bagchi1, Sukanta Misra2, Ashish Seal3 1 Senior Resident of Department of Obstetrics and Gynaecology,Vivekananda Institute of Medical Sciences Professor and Head of Department of Obstetrics and Gynaecology,Vivekananda Institute of Medical Sciences 3 Assistant Professor Consultant of Department of Obstetrics and Gynaecology,Vivekananda Institute of Medical Sciences 2 Received: 07/06/2019 Accepted: 12/07/2019 Published: 30/09/2019 Abstract Swyer syndrome or pure 46XY gonadal dysgenesis is a condition in which the individuals are phenotypically female; classically present as sexually infantile phenotypic females with primary amenorrhoea. The purpose of reporting this case is that it is extremely rare and the importance of diagnosis of females with gonadal dysgenesis for appropriate and early management. We are reporting a case of Swyer syndrome at Vivekananda Institute of Medical Sciences, Kolkata. The treatment required multi-disciplinary approach in terms of prevention of malignancy and osteoporosis, induction of puberty, fertility, and psychological support. Laparoscopy and gonadectomy being the mode of management as and when required, has been done in this case. Early diagnosis and management is extremely necessary as there is a high incidence of gonadal malignancies and also to discuss about fertility options; being an important aspect of these patients. Keywords: Swyer syndrome, Gonadal dysgenesis, Laparoscopy, Gonadectomy 1 Introduction1 Examination of secondary sexual characteristics revealed normalbreast development (Tanner’s Stage-IV) with normal areola. Axillary hair and pubic hairs were adequate. On inspection the external genitalia were of female type with normal vaginal orifice. Serum folliclestimulating hormone and serum luteinizing hormone were found to be high, 100 mIU/ml and 28.19 mIU/ml, respectively. Serum thyroid-stimulating hormone and serum prolactin were in normal range. CA-125 – 8.3 U/ml, Beta-hCG- 0.8mIU/ml, Alpha-fetoprotein – 1.2 ng/ml, were in normal limits. Ultrasound showed a rudimentary uterus and Magnetic Resonance Imaging revealed hypoplastic uterus with normal fallopian tubes and streak gonads, without endometrial or myometrial differentiation; both the kidneys were normal. Karyotype showed a genotype of 46XY. She was further subjected to diagnostic laparoscopy and the findings demonstrated a small uterus with normally present fallopian tubes. Bilateral inguinal canals were empty. Ovaries could not be visualized; fibrous band was seen on left side which could be streak gonads and on the right side we saw a mass of about (2*1*1) cm3. No other pelvic abnormalities were seen. Given streak gonads and genotype of XY, bilateral removal of whitish structures was done and sent for histopathology [Figure 1]. The right sided gonadal mass was also histopathologically characterized as dysgerminoma [Figure 2]. Swyer syndrome or complete gonadal dysgenesis was first described by Jim Swyer in 1955; since then, quite a number of patients were diagnosed and reported[1].It is characterized by bilateral streak gonads, normally developed Mullerian structures, phenotypically female external genitalia, genotype being 46XY and hypergonadotropic hypogonadism [2]. Patients usually present in adolescence with history of primary amenorrhea and with underdeveloped or absence of secondary sexual characters. The incidence of Swyer syndrome is 1:100,000 [3]. A child born with Swyer syndrome looks like a typical female. She usually does not develop secondary sexual characteristics without hormone replacement because streak gonads are incapable of producing the sex hormones (both estrogen and androgens). Hence the management of puberty in complete gonadal dysgenesis is similar to other causes of ovarian failure, i.e., initiation of estrogen to induce the development of secondary sexual characteristics and long-term combined replacement therapy with estrogen and progesterone. 2 Case report A 26 year old unmarried girl was referred to our department from the department of Endocrinology at Vivekananda Institute of Medical Sciences, Kolkata with history of primary amenorrhoea. She was on Ethinylestradiol (0.03 mg) and Levonorgestrel (0.15 mg) tablets since two years and was having regular menstruation. There was no history of cyclical abdominal pain, radiation exposure, chemotherapy, or any central nervous system symptoms such as headache or visual disturbances. There was no significant past history of surgery. She was the only child of a non-consanguineous marriage.On general examination, she was 164 cm tall and her body mass index was 24 kg/m2. 3 Discussion Swyer syndrome is a form of pure gonadal dysgenesis. The first known step of sexual differentiation of a normal XY fetus is the development of testes. The early stages of testicular formation in the 2nd month of gestation require the action of several genes, of which the most important is SRY, the sex-determining region of the Y chromosome. Four mutations of SRY account for many cases of Swyer syndrome. In most cases, the cause is not identified or may Corresponding author: Bishista Bagchi, Department of Obstetrics and Gynaecology, Vivekananda Institute of Medical Sciences. (RKMSP) E-mail: bishista.bagchi@gmail.com. 1 Journal of Infertility and Reproductive Biology, 2019, Volume 7, Issue 1, Pages: 1-3 The characteristic feature that differentiates Swyer syndrome from another disorder of XY females such as androgen insensitivity syndrome (AIS) is the higher propensity for malignant transformation. In Swyer syndrome, both internal and external genitalia are female, and there is hypergonadotropic hypogonadism, whereas in AIS, the external genitalia are female, internal are male, and they have hypogonadotropic hypogonadism. Because of the dysgenetic gonads, the risk of gonadoblastoma and dysgerminoma has been estimated to be between 15% and 35%, and it is advisable to perform bilateral gonadectomy as soon as the diagnosis is made [5]. This is in contrast with the management in another XY disorder such as AIS or true hermaphroditism that have a lower malignant potential. The main differential diagnosis of Swyer syndrome is mixed gonadal dysgenesis which is more frequently seen than the former. In this condition, the gonads on histopathology will also show testicular differentiation in addition to ovarian differentiation. The genotype too is usually a mosaic pattern. Swyer syndrome usually affects only sexual development; such cases are called isolated Swyer syndrome. However, depending on the genetic cause, Swyer syndrome may also occur along with health conditions such as nerve problems (neuropathy) or as part of a syndrome such as campomelic dysplasia, which causes severe skeletal abnormalities. Gonadoblastomas are seen in 20%–30% of women with Swyer syndrome [6]. be due to mutation of other genes in the sex differentiation pathway such as the autosomal genes DHH, MAP3K1, NR5A1, SOX9, WT1, DAX1 on the X chromosome [4]. When such a gene is mutated, the bipotential gonads fail to differentiate into testes in an XY fetus. Without testes, no testosterone or anti-Mullerian hormone (AMH) is produced. Without testosterone, there is no virilization of external genitalia, resulting in normal female genitalia. As AMH is absent, the Mullerian ducts develop into uterus, fallopian tube, cervix, and vagina. The diagnosis of Swyer syndrome is made around the time of puberty when the child who has been reared as a female is unable to achieve menarche and has delayed development of secondary sexual characters. People with Swyer syndrome have typical female external genitalia. The uterus and fallopian tubes are normally developed, but the gonads (ovaries or testes) are not functional; affected individuals have undeveloped clumps or strands of tissue called streak gonads. Due to the lack of development of the gonads, Swyer syndrome is also called 46, XY complete gonadal dysgenesis. The residual gonadal tissue often is seen to have malignant potential, so it is usually removed surgically early in life. Adrenal gland is not affected and can produce androgens and most of these patients develop pubic hair, though it often remains sparse. The diagnosis of Swyer syndrome was made in our case because she was a tall-statured girl with history of primary amenorrhea and sexual infantilism whose genotype was pure XY and the gonadal tissues are fibrous band. right sided gonadal mass Figure 1: Left sided streak gonads and right sided gonadal mass after excision Figure 2: Microphotograph showing dysgerminoma cells 2 Journal of Infertility and Reproductive Biology, 2019, Volume 7, Issue 1, Pages: 1-3 4 Conclusion Swyer syndrome is extremely rare and invariably causes primary amenorrhea. Genetic testing plays very important role in the diagnosis of Swyer syndrome. Early diagnosis, a minimally invasive approach to gonadectomy, followed by hormone therapy and family screening are the cornerstones of the management of this rare disorder. Early diagnosis is of crucial importance for various reasons, including the risk of gonadal malignancy and the need for removal of the gonads, early institution of hormonal therapy for induction of puberty, improving bone mineral density, and also counselling regarding fertility options. Menstrual function and pregnancy can be achieved in a selected group of patients. The Institutional Ethical Committee has granted ethical clearance for the study in accordance with the 1964 Helsinki Declaration. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. References 1. Hétu V, Caron E, Francoeur D. Hypoplastic uterus and clitoris enlargement in Swyer syndrome. J Pediatr Adolesc Gynecol. 2010;23:e43–5. 2. Granados H, Phulwani P. Absent visualization of a hypoplastic uterus in a 16 year old with complete 46 XY gonadal dysgenesis (swyer syndrome) Endocrinol Metab Syndr. 2013;2:1143. 3. Michala L, Goswami D, Creighton SM, Conway GS. Swyer syndrome: Presentation and outcomes. BJOG. 2008;115:737–41. 4. Hanley NA, Hagan DM, Clement-Jones M, Ball SG, Strachan T, Salas-Cortés L et al. SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development. Mech Dev. 2000;91:403–7. 5. Neena Malhotra, Vatsla Dadhwal, Kandala Aparna Sharma et al. The laparoscopic management of Swyer syndrome:Case series.J Turk Ger Gynecol Assoc.2015;16(4):252–256. 6. Coutin AS, Hamy A, Fondevilla M et al. Pure 46 XY gonadal dysgenesis. J Gynecol Obstet Biol Reprod.1996;25:7.92–6. 3