Prophylactic Gonadectomy Research Articles

Histologic analysis of gonadal tissue in patients with Turner syndrome and Y chromosome material

This study investigates gonadal histology in individuals with Turner syndrome assigned female at birth and Y-chromosome material (TS+Y) who underwent prophylactic gonadectomy. Despite case reports suggesting spontaneous menarche and pregnancies in TS+Y, this research reveals the absence of germ cells, indicating low fertility likelihood. Germ cell neoplasia in-situ was present in some patients, emphasizing a non-negligible risk of cancer precursor. As no malignancies were found even in older individuals, the study challenges the immediate need for prophylactic gonadectomy upon TS+Y diagnosis. Limited fertility benefits are suggested, emphasizing the need for further research on optimal timing and criteria for the procedure.

Pure 46, XY gonadal dysgenesis and 46, XY complete androgen insensitivity syndrome: A case report.

Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result from disorders of testicular development or androgen synthesis. We present 2 rare cases of 46, XY DSD, specifically XY pure gonadal dysgenesis and complete androgen insensitivity syndrome. Both cases underwent prophylactic gonadectomy due to the elevated risk of gonadal malignancy. Bilateral gonadoblastoma and dysgerminoma were diagnosed on one side, while Leydig cell hyperplasia and only Sertoli cells were diagnosed in the seminiferous tubules on both sides. The normal menstruation for the pure gonadal dysgenesis patient only as CAIS patients never menstruate. Estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation in pure gonadal dysgenesis case, as well as to prevent osteoporosis. Follow-up examinations revealed no tumor recurrence, and the patient with Swyer syndrome had regular menstrual cycles. Laparoscopic bilateral prophylactic gonadectomy and long-term hormone therapy with patient counseling and support are recommended.

A Case Report of 46 XY Partial Gonadal Dysgenesis with Dual Gonadal Tumours

46XY gonadal dysgenesis is known as a disorder of sex development (DSD) that occurs due to abnormality in gonadal development. There is a conflict between one’s genotype, phenotype, and gonadal development, which influences the wide range of presentation and clinical appearance of 46XY females. This was a case of a 46XY female who presented with primary amenorrhea with delayed puberty at the age of 18 years old. She had ambiguous genitalia. Her breast and pubic hair were at Tanner Stage 2. Transabdominal ultrasound found a small uterus with a vagina; however, the gonads were not seen. A magnetic resonance imaging (MRI) showed a 20mm right gonad located extra-pelvis near the right iliac vessels while the 9mm streak left gonad was at the usual location next to the sigmoid colon. All her tumour markers were normal except lactate dehydrogenase (LDH) was elevated. She was given estrogen therapy for pubertal induction and underwent laparoscopy prophylactic bilateral gonadectomy. The intraoperative findings were similar to the MRI findings, and the histopathology examination (HPE) results showed left gonadoblastoma and right dysgerminoma FIGO stage 1A. She continued taking estrogen therapy until she had withdrawal bleeding, and oral progesterone was added. 46XY-DSD has high risk of developing germ cell tumour and requires prophylactic gonadectomy as soon as the diagnosis is established. However, delay in presentation and surgery may affect the outcomes and prognosis.

Challenges in the management of Turner syndrome with Y chromosome material: a case report of prophylactic gonadectomy revealing dysgerminoma.

Turner syndrome (TS) patients with Y chromosome material face an increased risk of gonadal germ cell tumors (GCTs). This case report discusses the challenges in decision-making regarding prophylactic gonadectomy, considering the risk of malignancy and the desire to preserve fertility. We report a case of a 12-year-old female with mosaic TS and Y chromosome material who initially presented with short stature and obesity. Karyotype analysis showed a mixed cell line (45X and 46XY). Counseling about the increased risk of developing GCT and preservation of gonadal function was provided, and we decided to delay gonadectomy until the age of 12. Prophylactic bilateral gonadectomy revealed dysgerminoma associated with GB at the age of 12. Fortunately, the patient was asymptomatic, with no additional therapy required due to the early stage of the disease. The case highlights the dilemma in managing TS patients with Y chromosome material, where the risk of GCT varies depending on the type of difference in sex development and gonadal function. The decision to delay gonadectomy reflects the emphasis on preservation of ovarian, although it poses a risk of malignancy. This case underscores the importance of individualized care in TS patients with Y chromosome material, balancing the risk of malignancy against preservation of ovarian. It emphasizes the need for timely and personalized decision-making in prophylactic gonadectomy.

Prophylactic Gonadectomy, Malignancy Risk, and the Ethics of Parental Choices

Prophylactic Gonadectomy, Malignancy Risk, and the Ethics of Parental Choices

45,X/46,XY mosaicism: Clinical manifestations and long term follow-up.

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy.

Gonadoblastoma in Turner syndrome with puberty delay: A case report and literature review.

Y chromosome material stands as an independent risk determinant for the onset of gonadoblastoma (GB) and subsequent gonadal germ cell tumours in individuals with Turner syndrome (TS). However, the delayed and underestimated identification of Y chromosome material through karyotyping within primary care settings exacerbates the intricacies of managing these patients over the long term. We present a case involving TS accompanied by Y chromosome material, wherein puberty delay and GB were identified during prophylactic gonadectomy. Subsequently, we delve into the literature to explore the GB-related malignancy risk in TS patients with Y chromosome material, the incidence of Y chromosome presence in TS patients using methodologies beyond routine chromosomal testing, and the diagnosis and treatment of puberty delay in TS patients, all based on our case. A spectrum of more sensitive molecular techniques, including polymerase chain reaction (PCR) and fluorescence in situ hybridisation, effectively augments the detection of Y chromosome material alongside karyotyping. In addition to gonadectomy, the implementation of appropriate oestrogen therapy and a holistic, multidisciplinary approach to care can enhance the quality of life, while mitigating the long-term morbidity and mortality risks for TS patients harbouring Y chromosome material. Beyond gonadectomy, adopting a multifaceted approach the Y chromosome material detection, prompt initiation of puberty, tailored oestrogen therapy, and coordinated multidisciplinary management significantly contributes to the comprehensive health oversight of TS patients with Y chromosome material.

Consensus guide on prophylactic gonadectomy in different sex development

Consensus guide on prophylactic gonadectomy in different sex development

Undetectable anti-Mullerian hormone and inhibin B do not preclude the presence of germ cell tumours in 45,X/46,XY or 46,XY gonadal dysgenesis.

Individuals with 45,X/46,XYor 46,XYgonadal dysgenesis are at increased risk of germ cell malignancies. Therefore, prophylactic bilateral gonadectomy is advised in girls and considered in boys with atypical genitalia for undescended, macroscopically abnormal gonads. However, severely dysgenetic gonads may not contain germ cells rendering gonadectomy unnecessary. Therefore, we investigate if undetectable preoperative serum anti-Müllerian hormone(AMH) and inhibin B can predict the absence of germ cells, (pre)malignant or otherwise. Individuals who had undergone bilateral gonadal biopsy and/or gonadectomy because of suspected gonadal dysgenesis in 1999-2019 were included in this retrospective study if preoperative AMH and/or inhibin B were available. Histological material was reviewed by an experienced pathologist. Haematoxylin and eosin and immunohistochemical stainings for SOX9, OCT4, TSPY and SCF (KITL) were used. Thirteen males and 16 females were included, 20 with 46,XYand 9 with 45,X/46,XY DSD. Threefemales had dysgerminoma alongside gonadoblastoma; twogonadoblastoma, one germ cell neoplasia in situ (GCNIS) and three males had pre-GCNIS and/or pre-gonadoblastoma. Gonadoblastoma and/or dysgerminoma were present in 3/11 individuals with undetectable AMH and inhibin B, one of whom also had non-(pre)malignant germ cells. Of the other 18, in whom AMH and/or inhibin B were detectable, only one had no germ cells. Undetectable serum AMH and inhibin B cannot reliably predict the absence of germ cells and germ cell tumours in individuals with 45,X/46,XYor 46,XYgonadal dysgenesis. This information should help in counselling about prophylactic gonadectomy, taking into account both the germ cell cancer risk and potential for gonadal function.

Differences in gonadal tissue cryopreservation practices for differences of sex development across regions in the United States.

Some individuals with differences of sex development (DSD) conditions undergo medically indicated prophylactic gonadectomy. Gonads of individuals with DSD can contain germ cells and precursors and patients interested in future fertility preservation and hormonal restoration can participate in DSD-specific research protocols to cryopreserve this tissue. However, it is unclear how many providers or institutions offer gonadal tissue cryopreservation (GTC) and how widespread GTC for DSD is across the United States (US). The Pediatric Initiative Network (PIN) and Non-Oncologic Conditions committees of the Oncofertility Consortium sought to assess the current state of GTC for patients with DSD. An electronic survey was sent to providers caring for patients with DSD via special interest groups of professional societies and research networks. The survey was administered between November 15, 2021 and March 14, 2022.A total of 155 providers responded to the survey, of which 132 respondents care for patients with DSD, and 78 work at facilities that offer medically indicated gonadectomy to patients with DSD diagnoses. They represented 55 US institutions including 47 pediatric hospitals, and 5 international sites (Canada, Denmark, Germany, Qatar). Of individual providers, 41% offer cryopreservation after prophylactic gonadectomy for patients with DSD (32/78). At an institutional level, GTC after medically indicated gonadectomy is available at 54.4% (24/46) of institutions. GTC is offered for a variety of DSD diagnoses, most commonly 45,X/46,XY DSD (i.e., Turner Syndrome with Y-chromosome material and mixed gonadal dysgenesis), ovotesticular DSD, complete androgen insensitivity syndrome (CAIS), and complete gonadal dysgenesis. Responses demonstrate regional trends in GTC practices with 83.3% of institutions in the Midwest, 66.7% in the Northeast, 54.6% in the West, and 35.3% in the South providing GTC. All represented institutions (100%) send gonadal tissue for pathological evaluation, and 22.7% preserve tissue for research purposes. GTC after gonadectomy is offered at half of the US institutions represented in our survey, though a minority are currently preserving tissue for research purposes. GTC is offered for several DSD conditions. Future research will focus on examining presence and quality of germ cells to support clinical decision making related to fertility preservation for patients with DSD.

A Case Report of Turner Syndrome Diagnosed at Age 61 Years.

Here, we describe a case of Turner syndrome first diagnosed at 61 years of age. The patient's chief complaint was general edema. A cardiologist was consulted, who performed echocardiogram and coronary heart computed tomography. Chromosomal analysis yielded inconclusive results for Turner syndrome. The patient's karyotype was 45,X[17]/46,X,psu idic(Y)(q11.23), and she was referred to a gynecologist a time span. The patient was nulliparous with no history of sexual contact. We performed a prophylactic gonadectomy, but no malignancy was detected pathologically.

OR05-1 Testicular Magnetic Resonance Imaging (MRI) Findings and Predictive Factors of Gonadal Neoplasia in Complete Androgen Insensitivity Syndrome

Abstract Introduction Complete Androgen Insensitivity Syndrome (CAIS) is characterized by a complete external genitalia appearance and testicular development in 46,XY individuals carrying inactivating mutations in the AR gene. Prophylactic gonadectomy versus saving gonads has been debatable in CAIS management, mainly due to the absence of an accurate biomarker for testicular germ cell tumors (GCT). Objective to cross the preoperative pelvic MRI data with the histological gonadal findings from CAIS patients who underwent prophylactic gonadectomy to identify predictive factors of GCT development. Methods We evaluated 30 gonads from 15 CAIS patients with proven AR mutation. All performed pelvic MRI before gonadectomy through the same MRI machine and were included in the MRI data analysis. Three blinded radiologists specialized in urology performed image analysis. The immunohistochemical markers PLAP, c-KIT, OCT3/4, SALL4, ER, alpha-inhibin, CD99, and calretinin were performed. Results Nine (60%) performed gonadectomy after puberty (>16 years old). We identified one case of classical seminoma and one case of Sertoli cell neoplasia (at 18 and 19 years of age, respectively). Overall, the prevalence of neoplasia was 13.3%. No case of premalignant intratubular germ cell neoplasia was detected.Histological data revealed a high prevalence of benign lesions (n=12; 80%). Leydig Cell Hyperplasia (67%), stromal fibrosis (53%), Sertoli Cell nodules (47%), hamartomatoums nodules (40%) and paratesticular cysts (67%) which are more frequent after puberty (p<.01). MRI detected heterogeneity in all cases harboring hamartomatoums nodules, Sertoli cell nodules, and testicular neoplasia. Benign lesions were bilateral in all cases. Regarding the MRI data, the presence of testicular cystic mass (by tumoral necrosis) on MRI and tumor size (higher among malignancies) correlated with malignancy (p=.008 and p=.03, respectively), whereas gonadal location (inguinal/abdominal), presence of solid nodules, T2WI and postcontrast features, nodule diffusion restriction, and presence of perigonadal cysts did not. Chronological age >16 years was associated with malignancy with a 4.3 OR (1.6–11.69). Conclusion Pelvic MRI is sensitive to detect gonadal nodules in CAIS patients, regardless of the gonad position, but most nodules are benign. Testicular malignancy should be suspicious in the presence of testicular cystic mass and large testis size in CAIS patients >16 years old. Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.

A RARE CASE OF SECONDARY AMENORROHEA WITH SWEYERS SYNDROME: A CASE REPORT

Sweyers syndrome or pure gonadal dysgenesis is characterised by primary amenorrhea , presence of female phenotype, female external genitalia and female internal genitalia with hypoplastic uterus and streak gonads. A 16 year old girl presented with secondary amenorrhoea, she attained menarche at 11 years and was followed by 4 months of regular cycles thereafter developed two years of amenorrhea. On examination she is phenotypically female with no secondary sexual characteristics, external genitalia is female. Laboratory investigations showed a high level of serum follicle stimulating hormone, Luteinising hormone which were consistent with hyper gonadotropic hypogonadism, pelvic ultrasound showed a hypo plastic uterus and hypo plastic ovaries, chromosomal analysis revealed XY Karyotype. Further she underwent alaparoscopic prophylactic gonadectomy and the histopathology confirmed hypo plastic ovaries. In conclusion we emphasise that Sweyers syndrome can present with secondary amenorrhoea with a functioning uterus with lining endometrium. The importance of timely diagnosis and gonadectomy forseeing a gonadoblastoma cannot be over emphasised.

Gonadal tumor risk in pediatric and adolescent phenotypic females with disorders of sex development and Y chromosomal constitution with different genetic etiologies.

ObjectivesThis retrospective study sought to investigate the risk and proportion of gonadal neoplasms in phenotypic female pediatric patients with DSD and the presence of the Y chromosome and different genetic backgrounds in a single Chinese center.Materials and MethodsFrom January 2012 to December 2020, pediatric and adolescent patients with DSD and the presence of the Y chromosome who had unambiguous female genitalia and underwent bilateral gonadectomy or gonadal biopsy were included in this study. Patients’ demographics, karyotype, laboratory test results, gross pathology, and histology of gonadal tissue were all collected. The patients were divided into three groups based on their different genetic backgrounds, and the percentage of gonadal tumors was calculated to assess the risk of gonadal tumor and malignancy by etiology.ResultsA total of 22 patients with DSD and an unambiguous female phenotype with a Y chromosome were recruited. The mean age was 10.91 ± 4.99 years (9 months to 19 years). Gonadal neoplasia was confirmed in six (27.3%) cases by pathological examination of surgical gonadal tissue samples. Among 44 gonadal samples from these 22 patients, the following were identified: five gonadoblastomas, three dysgerminomas, and two Leydig cell tumors. The youngest patient with a tumor was a 2-year-old girl with 46,XY complete gonadal dysgenesis (46,XY CGD or Swyer syndrome) and bilateral gonadoblastoma. Patients with 46,XY complete gonadal dysgenesis (4/6; 66.7%) had the highest tumor occurrence rate. Among 10 patients with Turner syndrome with the presence of the Y chromosome, only one patient was diagnosed with a gonadal tumor. Leydig cell tumor was diagnosed in only one of six patients with 46,XY androgen synthesis/action disorders.ConclusionPediatric patients with 46,XY complete gonadal dysgenesis had a significantly increased risk of developing gonadal tumors and underwent prophylactic gonadectomy as soon as the diagnosis was confirmed, whereas those with Turner syndrome with Y chromosome and 46,XY androgen synthesis/action disorders had a relatively low risk. In view of the limited number of patients, a large multicenter study with close follow-ups is needed to support these conclusions.

009 46 XY: Management of the gonads

Women who have a Difference of Sex Development and Y chromosomal material in their (gonadal) karyotype are at increased risk for developing a malignant gonadal germ cell tumor (GCT). These GCT can be either seminomas (dysgerminomas) or non-seminomas and are always preceded by an in situ neoplastic lesion: germ cell neoplasia in situ in a (dysgenetic) testicular context or gonadoblastoma in a context of undifferentiated gonadal tissue. Therefore, prophylactic gonadectomy in childhood has long been a standard procedure.

Prophylactic gonadectomy in A young phenotypic female with turner syndrome 45,XO/46,XY mosaicism: a case report

Prophylactic gonadectomy in A young phenotypic female with turner syndrome 45,XO/46,XY mosaicism: a case report

A Rare Cause of Primary Amenorrhea: Swyer's Syndrome: A Case Report

Swyer syndrome is defined as pure XY gonadal dysgenesis (PGD). The phenotype is unequivocally female with a clinical history of primary amenorrhea and impuberty. We present a case of primary amenorrhea for which the etiological investigation revealed a 46XY karyotype. The patient was 34 years old and was admitted to the hospital for the development of primary amenorrhoea. On clinical examination, the patient had an adult female morphotype with a normal vulva. Hormonal work-up revealed hypogonado-hypergonadotropic, pelvic MRI: showed normal vagina and uterus with bilateral hypotrophic ovaries without follicles, complemented by a karyotype which showed 46XY on all metaphases analysed. The patient was put on oestrogen and vitamin supplementation and psychological counselling. A prophylactic gonadectomy was indicated for the patient. Swyer's syndrome remains a rare condition, even less so in the hierarchy of etiologies of primary amenorrhea. The performance of a karyotype in primary amenorrhoea has made this diagnosis possible. The risk of malignant transformation of undifferentiated gonads is high, requiring discussion of prophylactic gonadectomy as soon as the diagnosis is established. Complications of hypoestrogenism and psychological counselling are the other main areas of treatment. Up to now, egg donation remains the only alternative for infertility.

Swyer syndrome with malignant germ cell tumor: a case report

BackgroundSwyer syndrome (Pure gonadal dysgenesis, 46 XY) is a rare form of disorder of sexual development. These patients presented with external female phenotype, normal Mullerian structures and streak gonads. Pure gonadal dysgenesis, XY patients are more likely to develop germ cell tumors due to the presence of the Y chromosome.Case presentationA 19-year-old patient with a female external phenotype presented with primary amenorrhea. Clinical examination, Karyotyping, imaging, and histopathological assessment revealed Swyer syndrome. On imaging, a right adnexal mass with calcification was detected. Laparoscopic surgery with histopathology revealed a malignant germ cell tumor.ConclusionsSwyer syndrome represents a rare form of sexual development that necessitates a meticulous clinical, laboratory and radiological evaluation. Clinically, the patients have a female external phenotype with 46xy Karyotyping. Imaging, Ultrasound is the primary imaging modality Imaging and MRI helps in detection of the exact site of streak gonads and characterization of lesions. CT is useful in detecting calcification, which is a hallmark in the diagnosis of gonadoblastoma. Early diagnosis of Swyer syndrome is crucial as prophylactic gonadectomy in these cases reduces the risk of developing germ cell tumors.

EDITORIAL COMMENT

The authors quote a study that states the risk of tumor formation is 12% in TS if Y material is present. Other studies have similar but slightly lower risks of tumor occurrence in this subset of patients.1 The authors also acknowledge there are significant concerns about prophylactic gonadectomy. Which all leads to a question: What would the ultimate cancer mortality be for such patients if followed with serial imaging followed by gonadectomy if a tumor is found rather than prophylactic gonadectomy? To answer that question a national or multinational database would be needed and the patients followed for an extended time.

Malignant Germ Cell Tumors and Their Precursor Gonadal Lesions in Patients with XY-DSD: A Case Series and Review of the Literature

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’t 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.