Figure 2 - uploaded by Zhejun Cai
Content may be subject to copyright.
Histopathology of the gonadoblastoma. (A) Hematoxylin and eosin ×200 and (B) hematoxylin and eosin ×400. There is a biphasic population of germ cells and stromal cells arranged in nests. Hyalinization and calcification are present.
Source publication
What is the optimal protocol of management for phenotypic female patients with Y chromosome or Y-derived sequences, in particular for adult patients?
Immediate gonadectomy, long-term hormone therapy and psychological care are suggested to be the optimal management for older phenotypic female patients with Y chromosome or Y-derived sequences.
Phenot...
Context in source publication
Context 1
... of the gonadoblastoma showed biphasic population of germ cells and stromal cells which arranged in nests. Areas of hyaliniza- tion and calcification were present (Fig. 2). One patient had an early diagnosis of DSD at the age of 20 years without any neoplastic transform- ation. Fourteen years later, she presented with an abdominal mass, and a gonadoblastoma originating from right gonad without metastasis was confirmed after laparoscopic surgery and histopathological evaluation. Gonadoblastomas were ...
Similar publications
Noninvasive prenatal testing (NIPT) is commonly used to screen for fetal trisomy 13, 18, and 21 and often for sex chromosomal aneuploidies (SCAs). Although the testing is also used for sex chromosomal aneuploidies, it is not as efficient as it is for common trisomies. In this particular study, we present a case for whom the NIPT diagnosis was origi...
The aim of the present study was to determine the frequency and nature of chromosomal abnormalities involved in patients with the clinical spectrum of ambiguous genitalia (AG), amenorrhea, and Turner phenotype, in order to compare them with those reported elsewhere. The study was conducted in the Cytogenetic Department of Pasteur Institute of Moroc...
Disorders of or differences in sexual development (DSD) are defined by congenital conditions in which development of chromosomal, gonadal, or anatomic sex are atypical. Here, we report on monochorionic diamniotic twins delivered by Caesarean section in the 36th week of pregnancy. Monochorionic twins are usually monozygous and thus should have the s...
Citations
... We found out her actual genotype following those examinations.According to the hypothesis of our experts, this atypical development sex occurred by FFT during the fetal period, and afterward, she became a 46 XY female chimerism with unexpected fertile ability. Due to the rarity of DSDs, the Prophylactic gonadectomy is intended for Female patients with 46 XY karyotypes since they are predisposed to gonadal malignancy[27].The prophylactic gonadectomy was performed after examinations of immunohistochemistry, hormonal profile, ultrasound examination, molecular index, and cytogenetic analysis of the patient. Besides, these cases ought to be handled at specialized hospitals with expertise in diagnosis and treatment, along with a team of experts who can provide medical and surgical assistance. ...
Introduction: The mammalian Y chromosome is a vital sex-determining factor in mammals by encoding gonadal genes. However, there are some discordant conditions with the XY female chromosome, which can lead to their inclusion in the disorders of sex development group. Case Report: The person under study is a 22-year-old woman for whom written consent was obtained, and all ethical procedures were followed. Herein, we report an extraordinarily fertile adolescent phenotypic mother with congenital XY abnormality who reared as female, spontaneous puberty with regular menstruation and two gestations. This condition was initially diagnosed using the karyotype technique and finally confirmed with the specialized Fluorescence in-situ hybridization technique. Finally, the quantitative fluorescent polymerase chain reaction technique was used for more certainty. Usually, the male genotype cannot be fertile; since this case is unique, various reasons are involved in its occurrence. One of these cases can be a bone marrow or blood transplant, but according to the study, the possible development of this disorder can be caused by the fetal period. Conclusion: As the prior clinical history of the case report revealed that her twin brother died during her mother’s expectancies, it can be assumed that the blood supply between the two fetuses has been shared unevenly or that feto-fetal transfusion has occurred. This incident has caused her to become a chimera with XY karyotype.
... Additionally, there is a likelihood of long-term health complications, including but not limited to diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, celiac disease, hypothyroidism, and hepatic dysfunction (Gravholt et al., 2017). According to Liu et al. (2014), gonadectomy is advised in cases where certain cells exhibit Y chromosomal material. ...
Premature Ovarian Insufficiency (POI) is a pathological condition characterized by the cessation of ovarian function prior to an individual attaining the age of 40 years. This syndrome is marked by elevated levels of gonadotropins and diminished levels of oestrogen, ultimately leading to infertility. According to guidelines provided by the European Society for Human Reproduction and Embryology (ESHRE), diagnostic criteria for this condition include increased follicle-stimulating hormone (FSH) levels exceeding 25 IU/l tested on two separate occasions with a four-week interval between each measurement, together with the presence of amenorrhea or oligomenorrhea for at least 4 months. The occurrence of POI has been associated with adverse effects such as reduced fertility, irregular menstrual cycles, failed pregnancies, and a reduction in overall health-related quality of life. The early decline in oestrogen puts women at increased risk of osteoporosis, hypertension, cardiovascular disease, weight gain, type 2 diabetes, cognitive disorders such as Parkinson’s, depression, and Alzheimer’s disease, and dementia. In this respect, it has important consequences that negatively affect women. However, genetic abnormalities, metabolic problems, autoimmunity, iatrogenic causes, infections, or environmental variables have been identified that contribute to the development of premature ovarian failure syndrome in some patients. The etiopathogenesis of the disease remains largely unknown in the majority of cases. This review aims to review the available literature, focusing on the diagnosis, clinical aspects, causes, symptoms, complications, and treatment of POI.
... 14 A retrospective observational study analysed 30 patients with CAIS aged 16-34 years (mean age, 22.3 years) and found that nine patients had gonadoblastomas, giving a malignancy rate of 30%. 15 The most difficult problem in maintaining gonads is how to identify malignant gonads or carcinoma in situ early. Some scholars have proposed a screening plan, including regular imaging of the testes and serological examinations, ultrasonography or nuclear magnetic resonance examinations, alpha-fetoprotein, beta human chorionic gonadotropin, lactate dehydrogenase, optional placental alkaline phosphatase, LH, FSH, testosterone and inhibin B, but these are not specific detection methods for gonadal malignant transformation in CAIS patients. ...
Complete androgen insensitivity syndrome (CAIS) is a rare disease that can be easily misdiagnosed. Before puberty, this condition is easily misdiagnosed as an inguinal hernia. This case report describes a 31-year-old phenotypically female patient with CAIS who was misdiagnosed twice previously with an inguinal hernia. Her karyotype analysis showed that she was 46, XY. She underwent a bilateral gonadectomy and long-term hormone replacement therapy. A Leydig cell tumour of the right testis was diagnosed postoperatively. This report also reviews the current understanding of the diagnosis and treatment of CAIS.
... Gonadoblastomas are considered to be in situ germ cell neoplasms, which are associated with up to 50-60% risk of developing dysgerminoma. 99,103 Other germ cell tumors such as immature teratoma, seminomas, yolk sac tumors, embryonal carcinomas and choriocarcinoma can be encountered in patients with GD. [99][100][101][102][103] Approximately 6% of patients with Turner syndrome have a mosaic karyotype (partial fragments of the Y chromosome). 99 The majority of patients with Turner syndrome, who develop gonadal tumors are those with mosaic karyotype. ...
... Gonadoblastomas are considered to be in situ germ cell neoplasms, which are associated with up to 50-60% risk of developing dysgerminoma. 99,103 Other germ cell tumors such as immature teratoma, seminomas, yolk sac tumors, embryonal carcinomas and choriocarcinoma can be encountered in patients with GD. [99][100][101][102][103] Approximately 6% of patients with Turner syndrome have a mosaic karyotype (partial fragments of the Y chromosome). 99 The majority of patients with Turner syndrome, who develop gonadal tumors are those with mosaic karyotype. ...
... In conclusion, gonadal tumors often occur in females with GD and Y-chromosome or Y-derived sequences in their genome. 103 GD-related tumors have the same histological features as their non-syndromic counterparts. 31 Pathogenesis Genes DDX3Y and TSPY, which are localized on the proximal part of the short and long arms of the Y chromosome, are found in the majority of patients with gonadal dysgenesis and gonadoblastomas or germinoma. ...
Hereditary cancer syndromes are defined as syndromes, where the genetics of cancer are the result of low penetrant polymorphisms or of a single gene disorder inherited in a mendelian fashion. During the last decade, compelling evidence has accumulated that approximately 5-10% of all cancers could be attributed to hereditary cancer syndromes. A tremendous progress has been made over the last decade in the evaluation and management of these syndromes. However, hereditary syndromes associated with gynecologic malignancies still present significant challenge for oncogynecologists. Oncogynecologists tend to pay more attention to staging, histological type and treatment options of gynecological cancers than thinking of inherited cancers and taking a detailed family history. Moreover, physicians should also be familiar with screening strategies in patients with inherited gynecological cancers. Lynch syndrome and hereditary breast-ovarian cancer syndrome are the most common and widely discussed syndromes in medical literature. The aim of the present review article is to delineate and emphasize the majority of hereditary gynecological cancer syndromes, even these, which are rarely reported in oncogynecology. The following inherited cancers are briefly discussed: Lynch syndrome; "site-specific" ovarian cancer and hereditary breast-ovarian cancer syndrome; Cowden syndrome; Li-Fraumeni syndrome; Peutz-Jeghers syndrome; ataxia-telangiectasia; DICER1-syndrome; gonadal dysgenesis; tuberous sclerosis; multiple endocrine neoplasia type I, II; hereditary small cell carcinoma of the ovary, hypercalcemic type and hereditary undifferentiated uterine sarcoma; hereditary diffuse gastric cancer and MUTYH-associated polyposis. Epidemiology, pathogenesis, diagnosis, pathology and screening of these syndromes are discussed. General treatment recommendations are beyond the scope of this review.
... Dysgerminoma is the only germ cell malignancy that has this significant rate of bilaterality. [25] Although malignant and rapidly growing, they are often not aggressive and are highly sensitive to adjuvant chemotherapy, particularly with bleomycin, etoposide, and cisplatin given for three to four cycles. The survival rates of patients with XY gonadal dysgenesis and dysgerminoma are similar to the survival rates of XX individuals with malignant ovarian germ cell tumors. ...
... In this case, the combination of orchidectomy with penectomy allowed us to reduce an incision by resecting testes after degloving the penis skin and exposing the testes [5]. The incidence of gonadoblastoma in PAIS patients has been reported to range from 9.5 to 16.7%, indicating that orchidectomy is essential for the patient [10,11]. Thus, the orchidectomy has often been recommended to be performed early, preferably shortly after puberty. ...
Introduction and importance
The partial androgen insensitivity syndrome (PAIS) is a rare genetic disorder, which needs to be diagnosed early and provided suitable treatment. One-stage sex reassignment surgery can be considered as one of the treatment options for PAIS patients.
Case presentation
A 44-year-old patient with PAIS was admitted to our hospital. After getting a consultation, the patient decided to choose the one-stage sex reassignment surgery to be reassigned to be a female. The surgery consisted of breast augmentation and genital surgery. After 8 months of follow-up, the patient's breast had a desired shape and volume. The clitoris was in normal size with normal sensation, and the neovagina was 8 cm in depth with a smooth mucosal surface. We also observed that the minor labia were symmetric. The patient reported achieving orgasms with sex toys.
Clinical discussion
The one-stage sex reassignment surgery for the PAIS patient is safe and reduces treatment time for patients. It could also bring many benefits to the patients, such as reducing the incision, preventing gonadoblastoma and giving a sense of the patient's female gender which helps the patient feel confident and improve her quality of life. Thus, the one-stage surgery should be indicated for the patient at middle-aged who shouldn't be delayed anymore to have normal female breast and external genitalia.
Conclusion
The one-stage sex reassignment surgery was performed safely and successfully on the delayed presentation of the PAIS patient. This could be an effective and appropriate approach to treat late-diagnosed PAIS patients.
... A study by Liu et al has shown the chances of gonadal tumors like gonadoblastoma is as high as 30 % by the age 20 years. 10 On the other hand Cools et al showed that there were no chances of development of testicular tumors or even carcinoma in-situ and the occurrences of pre-germ cell neoplasia in situ (pre-GCIS) lesion was only 14% by 16 years of age. 11,12 Learning these data from studies on CAIS it would be better to carry out a biopsy of the testis if patients prefer gonadectomy in a later age. ...
Background: XY disorders of sex development are a complex entity that needs medical attention from childhood to adolescence and throughout life. The aim of the study was to analyze retrospectively the medical records of subjects with 46 XY disorders of sex development (DSD) and characterize their clinical profile and management course in a tertiary care centre.Methods: 32 subjects with 46 XY DSD attending Endocrinology OPD / Gynecology between 2010 to 2020 were enrolled in the study. Data collected includes age at presentation, symptoms, sex of rearing, phenotype, external masculinisation score (EMS), karyotyping, gonadal features like location and histopathology, psychosexual domain and their management and follow up. Statistical Analysis: The mean and standard deviation was calculated for normally distributed data.Results: The mean (SD) age of all study subjects (n=32) were 15.5 ± 5.32 years. 46 XY DSD included cases of complete gonadal dysgenesis (n=6), mixed gonadal dysgenesis (n=6), complete androgen biosynthetic defects (n=9), partial gonadal dysgenesis (n=2), 5-alpha-reductase type 2 deficiency (n=8) and 17 betahydroxysteroid deficiency (n=1). The most common clinical presentation was for primary amenorrhea followed by genital ambiguity and virilisation in females. Resection of testis at the earliest or a biopsy of the testis if resection is postponed in a female sex assigned 46 XY DSD is favored. Male sex assigned 46 XY DSD needs corrective surgeries and orchidopexy for undescented viable testis with periodic follow up for testicular malignancy.Conclusions: 46 XY DSD’s may shares similarities in their clinical presentation, though age of presentation may be in a wide range. Proper gender assignment, gonadectomy, reconstructive surgeries, hormone replacement and time to time follow up for testicular malignancy in cases where the testes are preserved is the ideal management.
... Data on gonadal biopsy or gonadectomy based on patient age at the procedure are presented in Table 1. 3,5,[11][12][13][14][15][16][17][18][19][20][21][22][23] Among the 15 studies analyzed, malignant lesions at gonadectomy were reported in 2 studies: Chaudhry et al. 5) described a 30-year-old patient with seminoma and a 68-yearold woman with primary amenorrhea and malignant sex cord stromal tumor. Huang et al. 23) found 4 patients with seminoma, all older than 20 years. ...
Complete androgen insensitivity syndrome (CAIS) is a rare condition characterized by 46,XY karyotype, female external genitalia, absence of uterus, and testes located intra-abdominally, in the inguinal ring or in the labia majora. In the present study, the frequency of testicular malignancy in prepubertal and pubertal patients with CAIS who underwent gonadectomy or gonadal biopsy were evaluated. Systematic review was performed using electronic databases according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. The samples included 15 articles published between 1998 and 2019. From a total of 456 patients who underwent gonadectomy or gonadal biopsy, 6.14% had a premalignant lesion and most were postpubertal (82.14%). A malignant lesion was found in 1.3% and all were postpubertal. Because the risk of malignancy is very low in prepubertal patients with CAIS, gonadectomy may be delayed until puberty is complete, allowing it to progress naturally; however, close follow-up of the patient is required.
... As a group, patients with DSD are at an increased risk for gonadal malignancy, as there is a well-established relationship between gonadoblastoma development, dysgenetic gonads, and the presence of Y-derived material. 12 Researchers speculated that some factors involved in the growth of dysgenetic gonads might be the same as those involved in the development of gonadoblastoma. 13,14 In another report, it was theorized that there is a gonadoblastoma locus in the Y chromosome that acts as a yet unidentified oncogene. ...
We present a case of a 13-year-old Filipino patient with ambiguous genitalia, randomly assigned as female at birth and was subsequently reared as such. Starting at 10 years of age, secondary male sexual characteristics emerged. However, medical consultation was sought only when the patient developed a gradually enlarging and painful abdominal mass. After cytogenetic studies, we are able to identify the case as Disorder of Sex Development, 45,X/46,X,der(Y) mosaicism, mixed gonadal dysgenesis. Further imaging, laparotomy and histopathology, revealed that the abdomino pelvic mass was from the right ovary, composed of immature teratoma. Ductus deferens and epididymis were also identified within the right ovary. At the time of presentation, the patient was already experiencing gender dysphoria. This report not only highlights the wide spectrum of phenotypes in mixed gonadal dysgenesis, but also stresses the importance of proper gender assignment during the newborn period in patients with disorders of sex development.
... It is considered that the number of germ cell tumours increases in individuals, simultaneous with AIS, because of the Y chromosome and presence of the testis-specific protein Y-linked 1 (TSPY) gene [40,41]. The literature in the field is not consensual, showing variation of the risks of malignancy in the case of AIS [42][43][44]. ...
Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.
