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The presence of Y chromosome material in patients with disorders of sex development (DSD) has been associated with a high risk of gonadoblastoma. Therefore, gonadectomy is recommended in females with bilateral streak gonads and Y chromosome material. The aim of this study was to present our experience with prophylactic gonadectomy in those patients...
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... Coyle et al. (6) observed GB in four of 14 patients, of whom only one was older than six years and the youngest was just five months. Matsumoto et al. (14) reported a series that included seven females with TS having Y-chromosome material, aged between 2 and 11 years. Pathologic examination revealed gonadal tumors in four subjects, the youngest of which was 2 years old. ...
Turner Syndrome (TS) is a chromosomal disorder with a karyotype of 45X.
However, by conventional karyotyping, Y-chromosomal material is known to
occur in up to 5-12% of TS patients; but it escalates to 60% when molecular
diagnostic tools are used. The most commonly investigated genes were SRY,
DYZ3, ZFY, and TSPY. Identifying the Y-chromatin in TS is important as it is
associated with the risk of developing germ cell tumors, especially gonadoblastoma (GB). The prevalence of GB in TS is variously reported as ranging
from 0 to 33%. As imaging studies cannot conclusively exclude malignancy of
abdominal gonads, prophylactic gonadectomy is recommended in TS patients
with Y-chromatin fragment. However, the optimal time of prophylactic gonadectomy is not known. The International Turner Syndrome Consensus Group
recommends gonadectomy at the time of diagnosis, regardless of age while
recent evidence suggest a more flexible approach, especially at puberty.
... Some risk factors have been suggested, including genetic syndromes such as Swyer syndrome [7,8], Down syndrome [9][10][11], Currarino syndrome defined by the triad of a presacral mass, sacral and anorectal congenital anomalies [12], or Klinefelter syndrome [13,14]. ...
GCTs are developmental tumors and are likely to reflect ontogenetic and teratogenetic determinants. The objective of this study was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were included. According to Teilum's holistic concept, malignant and benign teratomas were registered. We used a case-control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher's exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 16 isolated cases of eGCT with a wide range of syndromes. However, these were not found to be significantly associated following Bonferroni correction. Most of these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study, we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.
... Some risk factors have been suggested including genetic syndromes such as Swyer syndrome [6,7], Down syndrome [8][9][10], Currarino syndrome defined by the triad of a presacral mass, sacral and anorectal congenital anomalies [11], or Klinefelter syndrome [12,13]. Furthermore, the occurrence of eGCTs has been associated with non-syndromic defects as e.g. ...
GCTs are developmental tumors and likely to reflect ontogenetic and teratogenetic determinants. The objective was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were used. According to Teilum's holistic concept malignant and benign teratomas were registered. We used a case control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 17 isolated cases of eGCT with a wide range of syndromes, however not significantly associated following Bonferroni correction. All these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.
... GB develops almost exclusively in dysgenetic gonads in those with mosaicism with Y chromosome material, and in those with pure gonadal dysgenia [8]; furthermore, these constitute two-thirds of all gonadal tumours [9]. The general risk of developing GB in MTSY is approximately 15%-30%; however, it depends on age, ranging from 3% to 4% at 10 years to 46% at 40 years [3,7]. ...
... It typically affects children and young adults, with the majority of these detected prior to 15 years of age. Matsumoto et al [9] reported on a group of seven women with MTSY, aged 2-11 years, four of whom developed GB. ...
45,X/46,XY mosaicism is a sex development disorder with an estimated incidence of less than 1 in 15,000 live births. Various studies have shown there is an increased risk of germ cell tumours forming in Mosaic Turner syndrome. This includes gonadoblastoma, a clinically benign mixed germ-stromal cell tumour. However, this can later develop into one or several malignant germ cell neoplasms, for which early prophylactic gonadectomy is often recommended in patients with 45,X/46,XY mosaicism. The study presents the case of an 11-year-old patient diagnosed with a Mosaic Turner syndrome karyotype, who underwent prophylactic bilateral gonadectomy.
... Few data are available on the risk of gonadal malignancy in patients with DSD with female external genitalia, who are typically diagnosed with DSD at the time of gonadal tumor diagnosis (3). Although significant research has been conducted to improve knowledge about the risk of gonadal tumors, a limited number of studies have focused on the timing and indications of gonadectomy during childhood and adolescence in female patients with Y chromosome abnormalities (4)(5)(6)(7)(8). ...
... The optimal management of DSD in phenotypic females is especially controversial in the pediatric group, with differing views on the indications and timing for prophylactic gonadectomy (5,7,8). This single-center study reviewed the data of pediatric and adolescent phenotypic female patients with DSD harboring Y chromosomal material. ...
Objectives
This 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 Methods
From 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.Conclusion
Pediatric 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.
... EGCT is found to be associated with several genetic syndromes causing gonadal dysgenesis such as Klinefelter syndrome, Turner syndrome, and Swyer syndrome. [2][3][4] Those with EGCT appear to respond well to the treatment and can attain long term remission. The mainstay of treatment of EGCT is surgery, although chemotherapy may be beneficial in some cases which harbor a malignant component. ...
Objective: To determine the clinical features and treatment outcomes of pediatric extracranial germ cell tumor (EGCT) in Thailand.Materials and methods: A retrospective chart review of children under 15 years old with newly diagnosed EGCT who were treated at Faculty of Medicine Siriraj Hospital from January, 2004 to December, 2013 was conducted.Results: Forty-four patients were included in the study. The median age at diagnosis was 1.74 years (1 day-14.7 years) with the median follow up time of 6.9 years (14 days-15.2 years). Twenty-eight patients (64%) had extragonadal tumor. The most common primary tumor location was the sacrococcygeal area. Majority of the patients (61%) had malignant EGCT; yolk sac tumor was the most common diagnosis. Six patients (14%) had stage IV disease. Forty patients (91%) underwent surgery; 27 patients (61%) received chemotherapy. Thirty-eight patients (86%) achieved remission; 3 patients (7%) subsequently relapsed at a median time of 1 year. Eight patients (18%) died, mostly from tumor progression. The 5-year event-free survival (EFS) and overall survival (OS) rate were 78.3% and 81.1%, respectively. Patients achieving total tumor removal had significantly better 5-year EFS and OS. Cox regression analysis revealed that the adequacy of surgery was the only prognostic factor for survival. Conclusion: The survival rate of pediatric EGCT in our study was relatively favorable, but still inferior to that of developed countries. Novel therapy may be warranted for those patients who are unresponsive to the current treatment.
... Some studies have shown that the incidence of gonadal tumors is significantly higher in patients with DSD carrying the Y chromosome than in patients with other types of DSD and can reach 50% in patients with 46, XY DSD [2]. This may be related to abnormalities in the expression of SRY, SOX9, SF1, DAX1, WT1 and other genes located on the Y chromosome [3]. Gonadal tumors in these patients are mainly germ cell-sex cord stromal tumors and malignant germ cell tumors, including gonadoblastomas, asexual cell tumors, seminomas and Sertoli cell tumors [4]. ...
Background:
Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However, to the best of our knowledge, there are no publications in the existing literature that refer to the coexistence of 46, XY DSD and serous tumors in the ovary.
Case presentation:
Here, we report the case of a 23-year-old female (social gender) patient with 46, XY DSD presenting with primary amenorrhea. Imageology revealed a huge mass in the left adnexa. Subsequent pathological analysis revealed a serous borderline tumor of the ovary.
Conclusion:
Gonadal tumors of patients with 46, XY DSD are not necessarily malignant tumors and can coexist with borderline tumors with primitive corded gonads. The coexistence of DSD and serous borderline tumors is rare. Clearly, an early and accurate diagnosis plays an important role in the treatment of these patients. Although there may not be a clear correlation between the two lesions, it is vital that we specifically analyze the mechanisms involved so that we can determine whether patients with DSD are associated with an increase of developing serous borderline tumors of the gonad.
... Hence, the occurrence of GB in this young child with a low index of suspicion supports the current recommendations to proceed to gonadectomy as soon as the genetic diagnosis is made. Previous [20] and recent reports in under 3 years [21] , and as young as 9 months in 46,XY gonadal dysgenesis [22] . A recent report on GB in TMSY showed evidence of GB in a patient as young as 5 months and postulates that GB is diagnosed more commonly in the second decade of life due to later diagnoses of TMSY and consequent later elective gonadectomy procedures, rather than later new onset of GB. ...
Mosaic Turner syndrome (TSM) commonly occurs in the form of 45,X/46,XX and 45,X/46,X,i(X)(q10). Mosaicism for a Y chromosome, 45,X/46,XY, has been well documented and is associated with increased risk of gonadoblastoma (GB). To date, there are only six reported cases of TSM with a trisomy 18 karyotype, and only two of these were phenotypically female with 45,X/47,XY,+18 karyotype. We present the case of a phenotypically female infant born with dysmorphic features. G-banded karyotype and interphase FISH of blood showed 45,X in 95% and 47,XY,+18 (trisomy 18) in 5% of cells analysed. However, interphase FISH of buccal cells showed only the presence of the 45,X cell line. Due to the presence of Y chromosome material, elective gonadectomy was performed at 13 months of age. There were bilateral streak ovaries with early evidence of GB bilaterally, a rudimentary uterus and bilateral fallopian tubes with unilateral ectopic adrenal tissue identified histologically. Interphase FISH of the gonadal tissue was similar to the blood findings with 45,X in 86% of cells and 47,XY,+18 in 14% of cells analysed. This case highlights a rare karyotype of TSM and trisomy 18 in the same patient and is the first reporting the associated finding of bilateral GB.
... The age profile of our study population is generally younger than that seen in most other series; however, we have observed GB in four of 14 patients, only one of whom was older than 6 years and the youngest of whom was just 5 months. Matsumoto et al. [21] reported a series that included seven females with TMSY, aged between 2 and 11 years. Four females had GB, including two who had dysgerminoma in one gonad [21]. ...
... Matsumoto et al. [21] reported a series that included seven females with TMSY, aged between 2 and 11 years. Four females had GB, including two who had dysgerminoma in one gonad [21]. The fact that GB is thought to most commonly occur in the second decade of life may be a result of later diagnosis of TMSY in other series, leading to later prophylactic gonadectomy [12]. ...
Background:
It is recognised that individuals with a 45,X/46,XY karyotype, known as Turner mosaic syndrome with Y chromosome material (TMSY), have an increased risk of developing gonadoblastoma (GB), which may then devolve into one of a number of germ cell malignancies. Hence, children with TMSY are usually recommended to undergo prophylactic gonadectomy.
Objective:
We designed this study to describe the phenotypic features of our series of children with TMSY who underwent prophylactic gonadectomy in order to evaluate the prevalence of GB and germ cell malignancies in their resected specimens.
Study design:
This is a retrospective case series wherein we comprehensively reviewed the clinical, histological, and cytogenetic features of all patients who underwent prophylactic gonadectomy at three tertiary paediatric referral centres over 16 years. Cases were identified from surgical logbooks and through the institutional histopathology database. Data were collected with particular reference to clinical phenotype, predominant karyotype cell line, operative management, anatomical findings and the presence of neoplastic changes.
Results:
Fourteen children ranging in age at the time of surgery from 2 weeks to 17 years were included in the series. Eleven children were reared as females. The three children who were reared as males had severe penoscrotal hypospadias. The 46,XY cell line was the predominant cell line in seven (50%) cases in blood lymphocytes. The resected specimens from four patients (28.6%) contained GB, with three patients having bilateral GB. This sub-group of patients with GB were aged 5 months, 48 months, 71 months, and 13 years. GB arose in one patient with and three patients without genital virilisation. There was no focus of invasive germ cell tumour in any specimen.
Discussion:
GB may be present in infants with TMSY as young as 5 months, even with low levels of Y chromosome material. The prevalence of GB in prophylactic gonadectomy specimens is similar to many previously reported series, although the absence of dysgerminoma in our series is reassuring. The exclusive presence of GB in intra-abdominal gonads is in keeping with the findings of several other series.
Conclusion:
Owing to the presence of gonadoblastoma in the gonads of children with TMSY as young as 5 months, we recommend that all patients with intra-abdominal gonads in the context of TMSY should duly undergo prophylactic gonadectomy, although the timing of such surgery can be discussed with parents during counselling regarding the risk of malignancy.
... 6 In another study with 11 patients with sexual differentiation disorders, 7 had Turner phenotype and mosaic karyotype Y in peripheral blood. 7 All patients with TS underwent gonadectomy, and histopathological findings revealed that four of them (57.1%) had gonadoblastoma, and in two cases it was associated with dysgerminoma. 7 Regarding the classical cytogenetic analysis by GTG banding, peripheral blood lymphocytes are the material of choice because it is easy to harvest this tissue, and the analysis is usually performed in 30 metaphases, which allows detection of 10% of mosaicism. ...
... 7 All patients with TS underwent gonadectomy, and histopathological findings revealed that four of them (57.1%) had gonadoblastoma, and in two cases it was associated with dysgerminoma. 7 Regarding the classical cytogenetic analysis by GTG banding, peripheral blood lymphocytes are the material of choice because it is easy to harvest this tissue, and the analysis is usually performed in 30 metaphases, which allows detection of 10% of mosaicism. 8 The advantage of molecular methods is that it require no cell culture and only a small sample for analysis and are more sensitive to detect low mosacismo, frequent in TS. 8 Thus, the aim of this review is to present the prevalence of Y chromosome sequences by molecular techniques and gonadoblastoma in patients with TS. ...
... The youngest patient with TS submitted to gonadectomy was 2 years old. 7 According to data presented, it can be concluded that molecular investigation is indicated for Y-chromosome sequences in TS patients, regardless of the karyotype, as a complement to the cytogenetic diagnosis. PCR is the technique suggested because it is inexpensive, sensitive, rapid, and enable the tracking of various sequences of Ychromosome simultaneously. ...
Objective:
To assess the prevalence of Y-chromosome sequences and gonadoblastoma in patients with Turner syndrome (TS) using molecular techniques.
Data source:
A literature search was performed in Pubmed, limiting the period of time to the years 2005–2014 and using the descriptors: TS and Y sequences (n=26), and TS and Y-chromosome material (n=27). The inclusion criteria were: articles directly related to the subject and published in English or Portuguese. Articles which did not meet these criteria and review articles were excluded. After applying these criteria, 14 papers were left.
Data synthesis:
The main results regarding the prevalence of Y-chromosome sequences in TS were: (1) about 60% of the studies were conducted by Brazilian researchers; (2) the prevalence varied from 4.6 to 60%; (3) the most frequently investigated genes were SRY, DYZ3 and TSPY; (4) seven studies used only polymerase chain reaction, while in the remaining seven it was associated with FISH. Nine of the 14 studies reported gonadectomy and gonadoblastoma. The highest prevalence of gonadoblastoma (33%) was found in two studies. In five out of the nine papers evaluated the prevalence of gonadoblastoma was 10–25%; in two of them it was zero.
Conclusions:
According to these data, molecular analysis to detect Y-chromosome sequences in TS patients is indicated, regardless of their karyotype. In patients who test positive for these sequences, gonadoblastoma needs to be investigated.
