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Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype–phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations. [ABSTRACT FROM AUTHOR]

Mixed gonadal dysgenesis (MGD) is a disorder of sex development caused by mosaicism of the Y chromosome, represented by 45,X/46,XY. Prophylactic gonadectomy is recommended as soon as possible after its diagnosis, owing to a high risk of malignancy. In the present case, a 21-year-old woman presented with primary amenorrhea. Although the patient's external genitalia were female, the patient exhibited a hypoplastic uterus, wherein the ovaries were difficult to identify. The patient's height was 146 cm; they had cubitus valgus and webbing of the neck, leading to the consideration of a disorder of sex development. Chromosomal examination revealed 45,X/46,XY mosaicism. Thus, the patient was diagnosed with MGD. After thorough counseling, laparoscopic bilateral gonadectomy was performed. Pathological examination revealed a gonadoblastoma of the left gonad. Postoperatively, the patient had no recurrence and continued on Kaufmann therapy. In conclusion, prophylactic gonadectomy is recommended immediately following a diagnosis of MGD; however, the timing of the surgery should be carefully considered and adequate counseling should be conducted by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Swyer syndrome is a rare genetic disorder in which gonadal dysgenesis and karyotype 46, XY are observed. In the postnatal and prepubescent period, this disease has no clinical manifestations and is asymptomatic, which makes diagnosis difficult. The first signs of the syndrome appear in puberty in the form of underdevelopment of secondary sexual characteristics. This review presents the criteria based on which such a diagnosis as Swyer syndrome can be made. The main diagnostic methods are highlighted, the possibilities of both surgical treatment of patients and drug treatment due to hormone replacement therapy are considered. Verification of the syndrome contributes to a more thorough examination, which will allow you to determine management tactics and avoid complications from other organs and systems.

Abstract A 27-year-old man was admitted to the hospital after a year of marriage due to infertility. During laparoscopic exploratory surgery, the presence of a retrovesical uterus was clearly observed, and the gonadal organs were visible on both sides. However, the testicles or ovaries were not identifiable, nor were the spermatic vessels and fallopian tubes at the joint. Intraoperative bilateral gonad biopsy was performed. Cryopreservation of the right gonadal gland revealed gonadoblastoma and malignant germinoma (asexual tumor/seminoma) with sclerosis and atrophy of testicular tissue. No proliferation of germ cells and sertoli cells was observed in spermatic tubule. The left gonad was diagnosed as a gonadoblastoma. Finally, total hysterectomy and bilateral gonadal tumor organectomy were performed to seal the vaginal stump. Local radiotherapy was administered after surgery. In general, tumors were found on both sides of the gonads, especially gonadoblastoma and malignant germinoma on the right side and gonadoblastoma on the left side.

A 27-year-old man was admitted to the hospital after a year of marriage due to infertility. During laparoscopic exploratory surgery, the presence of a retrovesical uterus was clearly observed, and the gonadal organs were visible on both sides. However, the testicles or ovaries were not identifiable, nor were the spermatic vessels and fallopian tubes at the joint. Intraoperative bilateral gonad biopsy was performed. Cryopreservation of the right gonadal gland revealed gonadoblastoma and malignant germinoma (asexual tumor/seminoma) with sclerosis and atrophy of testicular tissue. No proliferation of germ cells and sertoli cells was observed in spermatic tubule. The left gonad was diagnosed as a gonadoblastoma. Finally, total hysterectomy and bilateral gonadal tumor organectomy were performed to seal the vaginal stump. Local radiotherapy was administered after surgery. In general, tumors were found on both sides of the gonads, especially gonadoblastoma and malignant germinoma on the right side and gonadoblastoma on the left side. [ABSTRACT FROM AUTHOR]

45,X/46,XY mosaicism is a rare condition with clinical and genetic heterogeneity and have a greatly increased risk of developing germ cell tumors. We describe a rare 45,X/46,XY Chinese girl with malignant tumors, especially focusing on the molecular genetics of gonadal tumor. We report a phenotypically Turner-like Chinese adolescent girl who presented primary amenorrhea and a pelvic mass as the chief complaint, which finally demonstrated dysgerminoma replacing the left gonad and gonadoblastoma arising from right gonad respectively. Her chromosome karyotype was 45,X(4)/46,XY(46); Y-chromosome microdeletions in AZFb regions were found on gonadal DNA rather than peripheral blood lymphocyte (PBL) DNA, while no variants were found in the promoter and coding region of SRY gene in both PBL and gonadal tissues. She underwent bilateral gonadectomy; no recurrence or serious complications were identified after 3 years of follow-up. This case emphasizes the probable correlation between Y chromosome microdeletions in gonadal tissue and the severity of the phenotype in patients with 45,X/46,XY mosaicism and highlights the importance of clinical genetic testing at the chromosomal and molecular level. [ABSTRACT FROM AUTHOR]

A complete gonadal dysgenesis (CGD) with 46,XY karyotype is known as the Swyer syndrome and belongs to the group of 46,XY differences of sex development (DSD). The main problem in patients with Swyer syndrome is the delayed puberty and primary amenorrhea. Moreover, intrabdominal dysgenetic gonads in the patient with genetic material of a Y chromosome may conduce to the development of gonadal tumors, such as gonadoblastoma or germinoma. The management of such patients is based on preventive excision of dysgenetic gonads and long-term hormonal replacement therapy. Sporadic cases are considered more common than familial cases. This paper presents two siblings with Swyer syndrome in whom gonadoblastoma was found. A thorough review of familial CGD with 46,XY DSD in the literature from the last 15 years suggests that the risk of gonadal tumors could be increased in familial compared to sporadic cases (66.6% vs. 15–45%, respectively). [ABSTRACT FROM AUTHOR]

Introduction: The presence of Y-chromosomal material in females with Turner syndrome (TS) is a well-established risk factor for developing gonadoblastoma and malignant transformations thereof. However, these events are rarely seen in TS patients with no Y-chromosomal material. Thus, it is the current understanding that parts of the Y-chromosome are essential for the malignant transformation of gonadoblastoma in the dysgenetic gonad. Methods: We report a case of a TS female with an apparent 46,X,idic(Xq) karyotype, who was diagnosed with a metastatic dysgerminoma. Whole exome sequencing of the tumor and blood, along with RNA sequencing of the tumor, was performed to comprehensively search for cryptic Y-chromosomal material and pathogenic variants. Results: No Y-chromosomal material was detected in either tumor or blood. Whole exome-sequencing of DNA and RNA revealed a pathogenic somatic gain-of-function mutation in KIT and a pathogenic missense mutation in MTOR. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, followed by adjuvant chemotherapy. Unfortunately, she died due to chemotherapy-induced pneumonitis 7 months after the initial diagnosis. Conclusion: Females with TS can develop metastatic dysgerminoma even in the absence of Y-chromosomal material. This questions the current understanding of Y-chromosomal material being essential for the malignant transformation of a gonadoblastoma in the dysgenetic gonad. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: Children with 45X/46XY difference/disorder of sex development (DSD) have varying internal/external genitalia/gonads, Turner-like features, and increased risk of gonadal malignancy. We present a case of concomitant virilization and feminization as a unique feature of gonadoblastoma in a boy with 45X/46XY DSD. Case presentation: The patient was born with ambiguous genitalia (phallus of 2cm, perineal urethra) and a Turner-like phenotype. Ultrasound scan revealed horseshoe kidneys, intra-abdominal gonads, and Mullerian remnants. His karyotype was 45X/46XY with atypical Y chromosome. Initial gonadotrophin levels were very high. Biopsy of the bilateral gonads revealed testicular tissue. It was decided to raise the baby as a boy. Staged orchidopexy and hypospadias repair were done between 4 and 6 years of age. He remained under close clinical, biochemical and radiological follow-up for the potential development of gonadal malignancies. He developed penile enlargement at the age of11 years. Within a few months, he developed bilateral gynecomastia and rapid cystic enlargement of the gonads. Hormone quantification revealed elevated serum estrogen, a peri-pubertal testosterone level, and normal tumor marker levels. After a multidisciplinary team discussion, he underwent surgical exploration and removal of a bulky uterus and both gonads. Histology showed evidence of gonadoblastoma within the testicular and the ovarian stroma. Conclusion: Children with DSD are at high risk for developing gonadoblastomas, which can present as rapid concurrent isosexual and heterosexual pubertal development. It is critical that patients with DSD remain under close oncologic surveillance.

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

Swyer syndrome is a condition where individuals with a 46XY karyotype, typically associated with males, display complete gonadal dysgenesis and lack testicular differentiation. This results from a mutation in the SRY gene, which is essential for testis development. As a consequence, affected individuals who appear phenotypically female have male chromosomes but do not develop functional testes. As a result, there is an absence of testosterone that leads to lack of masculinization and the presence of female genitalia. This article describes a 20-year-old female from Pakistan who exhibited primary amenorrhea. On examination, she possessed a typical female physique but lacked breast growth and axillary hair. She had scant pubic hair with female-type external genitalia. The pelvic imaging showed a underdeveloped uterus, along with small ovaries and fallopian tubes. Her karyotype came out to be 46XY. The examination and radiological results indicated Swyer syndrome. During laparoscopy, the patient's uterus was found to be infantile, while the fallopian tubes were healthy. Streak gonads were also present, and due to the risk of gonadoblastoma, they were surgically removed. Hormone replacement therapy was started to induce pubertal development and optimize bone mineral accumulation. [ABSTRACT FROM AUTHOR]

Turner syndrome (TS) is a congenital chromosomal abnormality that affects approximately 1 in 2,500 people. Both in China and abroad, few studies exist on the incidence of tumors in patients with TS. Most reported cases are complicated with gonadal germ cell tumors, and extragonadal tumors are rare, with the latter not yet being reported in China. Through chromosome karyotype analysis and surgical exploration, a pediatric patent was diagnosed with TS complicated with gonadoblastoma and adrenal neuroblastoma. The patient was short in stature and had a facial deformity. After admission, adrenal computed tomography was conducted, and a right adrenal mass was identified as a neurogenic tumor. After surgical resection and gonadal exploration, the pathological results revealed left gonadoblastoma, right gonadal stromal cell hyperplasia, and ganglion neuroblastoma (mixed type) in the right adrenal gland. Pediatric patients with TS have an increased likelihood of developing neuroblastoma and adrenal-related tumors, and changes in adrenal hormone levels and clinical manifestations are often not obvious when combined with adrenal-related tumors. To avoid missed diagnosis and delayed treatment, screening for adrenal tumors is therefore recommended for patients with TS before the initiation of growth hormone treatment.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the NBN gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Nibrin is also involved in gonadal development and its disfunction in females with NBS frequently results in a pure gonadal dysgenesis (PGD) causing hypergonadotropic hypogonadism. However, only a few ovarian tumors in NBS patients have been reported to date. We describe the first case of a girl with NBS with PGD, who developed metachronous bilateral ovarian germ cell tumors (dysgerminoma and gonadoblastoma). Pathogenesis of PGD, neoplastic transformation and therapeutic approach in females with NBS are discussed.

Background: WT1 deletions are associated with nephroblastomas, WT mutations are associated with 46, XY sex reversal. It is unclear why only a few WT1 deletions are associated with sex reversal. Case report. This 46, XY female had a 15.2 MB interstitial deletion of 11p14.1p11.2, which included WT1 and FSHB. No pathogenic abnormalities were identified in 156 other genes associated with disorders of sexual development. Bilateral gonadoblastomas were incidentally diagnosed at 17 months of age at the time of prophylactic gonadectomies. She was treated without biopsy for bilateral nephroblastomas radiologically identified at 18 months of age. Bilateral partial nephrectomies contained treated intralobular nephrogenic rests. Conclusion: It is unclear why WT1 deletions are less associated with 46, XY sex reversal than WT1 mutations. Treating suspected nephroblastomas without biopsy, even in patients with syndromes associated with bilateral nephroblastomas, may still lead to diagnostic and therapeutic uncertainties. [ABSTRACT FROM AUTHOR]

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Objective: The literature regarding gonadoblastoma risk in exonic Wilms’ tumor suppressor gene (WT1) pathogenic variants is sparse. The aim of this study is to describe the phenotypic and genotypic characteristics of Asian–Indian patients with WT1 pathogenic variants and systematically review the literature on association of exonic WT1 pathogenic variants and gonadoblastoma. Design: Combined retrospective–prospective analysis. Methods: In this study, 46,XY DSD patients with WT1 pathogenic variants detected by clinical exome sequencing from a cohort of 150 index patient s and their affected relatives were included. The PubMed database was searched for the literature on gonadoblastoma with exonic WT1 pathogenic variants. Results: The prevalence of WT1 pathogenic variants among 46,XY DSD index patients was 2.7% (4/150). All the four patients had atypical genitalia and cryptorchidism. None of them had Wilms’ tumor till the last follow-up, whereas one patient had late-onset nephropathy. 11p13 deletion was present in one patient with aniridia. The family with p.Arg458Gln pathogenic variant had varied phenotypic spectrum of Frasier syndrome; two siblings had gonadoblastoma, one of them had growing terato ma syndrome (first to report with WT1). On literature review, of >100 exonic point pathogenic variants, only eight variants (p.Arg462Trp, p.Tyr177*, p.Arg434His, p.Met410Arg, p.Gln142*, p.Glu437Lys, p.Arg458*, and p.Arg458Gln) in WT1 were associated with gonadoblastoma in a total of 15 cases (including our two cases). Conclusions: WT1 alterations account for 3% of 46,XY DSD patients in our cohort. 46,XY DSD patients harboring exonic WT1 pathogenic variants carry a small but definitive risk of gonadoblastoma; hence, these patients require a gonadoblastoma surveillance with a more stringent surveillance in those harboring a gonadoblastoma-associated variant.

Turner syndrome is a chromosomal disorder affecting females characterized by the partial or complete absence of one X chromosome. The pathogenesis of Turner syndrome primarily arises from chromosomal nondisjunction during gametogenesis, leading to various genotypic presentations. The most common genotype is 45, XO, representing a monosomy of the X chromosome. However, mosaicism, where different cell lines carry distinct chromosomal compositions, is also observed in some cases. This paper presents a case of prenatal diagnosis of Turner syndrome mosaicism with a genotype of 45, XO/46, XY. The patient, initially managed by her obstetrician/gynecologist, was referred to a perinatologist at 20 weeks and four days of gestation due to multicystic kidney findings in the fetus. Initial non-invasive prenatal testing (NIPT) suggested trisomy 22, but confirmation through amniocentesis revealed mosaic Turner syndrome (45, XO/46, XY). The pregnancy culminated in the delivery of a phenotypically female infant at 39 weeks gestation. Mosaic 45, XO/46, XY presents with a broad spectrum of phenotypic variability, ranging from classic Turner syndrome features to ovotesticular disorder and genital ambiguity, and even male genitalia with infertility. Patients with mosaic Turner syndrome require multidisciplinary follow-up due to the complexity of their condition. Additionally, the presence of Y chromosome material significantly elevates the risk of gonadoblastoma, necessitating consideration of prophylactic gonadectomy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abulatan et al.)

Gonadoblastoma is a rare ovarian tumor composed of sex cord cells and primitive germ cells. While the majority of gonadoblastomas are found in individuals with 46,XY gonadal dysgenesis, they are also rarely seen in patients with a 46,XX karyotype. We report a case of a fourteen-year-and-six-month-old girl presenting with an uncommon cause of virilization due to a virilizing ovarian tumor. The patient underwent bilateral salpingo-oophorectomy. Upon histopathological examination, the excised tumor was confirmed to be bilateral gonadoblastoma, with dysgerminoma on the left side. Malignant gonadal tumors should be considered in cases of primary gonadal insufficiency with a 46,XX karyotype and progressive virilization. Even when laboratory and imaging tests show no abnormalities, a gonadal biopsy should be considered.

We report a rare case of bilateral HCG-secreting gonadoblastomas (Gb) in a 5.25-year-old girl of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism. The clinical data were summarized, and the literatures were reviewed. The patient had enlarged breasts for 2 years and 3 months, with elevated β-HCG of blood found for 8 months. The level of β-HCG of cerebrospinal fluid, cranial MRI, chest and abdominal CT, and pelvic MRI were normal. After surgical gonad exploration, biopsy and excision, gonad venous blood hormone examination and SRY gene detection of gonad tissue, the diagnosis was confirmed as HCG-secreting Gb (bilateral) and TS (45, X) with gonad Y chromosome mosaicism. The patient received 4 courses of chemotherapy, and regular outpatient follow-up. At 9 months after gonadectomy, there was no clinical, laboratory, or radiological evidence of recurrence. We reported a nonclassical case of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism, who presented with breast development as the first manifestation and then virilization due to bilateral HCG-secreting gonadoblastomas. Detection of serum β-HCG and AFP is requisite for the diagnosis of precocious puberty, karyotyping is important for virilizing phenotypic female, and virilization in Turner syndrome implies the existence of Y chromosome(substance) (peripheral blood or tissue mosaicism) and the occurrence of gonadal tumors.

Turner syndrome (TS) is a sex chromosome condition characterized by complete or partial loss of the X chromosome. Patients with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype are predisposed to gonadoblastoma with malignant transformation. We present the case of a TS patient with 45,X/46,XY with 2 episodes of left adnexal torsion (AT). Biopsies during detorsion showed benign mucinous cystadenoma. Pathology following bilateral gonadectomy revealed a left gonad with mucinous borderline tumor and right gonad with gonadoblastoma, both of which have malignant potential. Gonadectomy is recommended in XY gonadal dysgenesis to decrease risk of malignant transformation from gonadoblastoma. Although rare in pediatric patients, ovarian malignancies have been identified among AT cases. To our knowledge, we present the first case of AT due to borderline ovarian mucinous tumor of the ovary and contralateral gonadoblastoma in a patient with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype. [ABSTRACT FROM AUTHOR]

Introduction: 46,XY pure gonadal dysgenesis (PGD) is also known as Swyer syndrome. The chromosome analysis indicates a 46,XY karyotype. As different degrees of gonadal hypoplasia or degeneration occur in the process of embryonic development due to several factors, gonadal dysplasia or gonadal tumors are probable. Case Presentation: The patient was a 22-year-old female with no menstruation during puberty. Her chest was funnel-shaped, the breast development was classified as Tanner III grade, the vulva was normal, the pubic hair was classified as Tanner II grade, and the vaginal long was 6 cm. The endocrine examination indicated a follicle-stimulating hormone level of 95.0 mIU/mL and an estradiol level of 34.0 pg/mL. Tumor markers, including alpha-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and carcinoembryonic antigen (CEA), were normal. Dual-energy X-ray absorptiometry revealed that the bone mineral density was lower than the normal range at this age. Ultrasonography showed a hypoechoic mass in the left adnexal area, considering gonadal tissue with calcification. Pelvic MRI indicated a gonadal malignancy, and the gonadal tissue of the right adnexal area was cord-shaped. The chromosome analysis indicated a 46,XY karyotype. Accordingly, a clinical diagnosis of PGD was established. Moreover, laparoscopic gonadectomy and pathological examination were performed, and a final diagnosis of Swyer syndrome, complicated with a left-sided gonadoblastoma and asexual cell tumor, was made. Conclusion: PGD is associated with a high risk of gonadal tumors. Considering the rarity of this disease, a detailed evaluation of gonadal size and timely preventive gonadectomy are recommended for patients with gonadal dysplasia. Overall, imaging examinations can provide important information for the diagnosis of gonadal dysplasia. MRI can clearly indicate the size and shape of the gonads and the tumor, as well as the relationship between the tumor and the surrounding tissue. [ABSTRACT FROM AUTHOR]

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the NBN gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Nibrin is also involved in gonadal development and its disfunction in females with NBS frequently results in a pure gonadal dysgenesis (PGD) causing hypergonadotropic hypogonadism. However, only a few ovarian tumors in NBS patients have been reported to date. We describe the first case of a girl with NBS with PGD, who developed metachronous bilateral ovarian germ cell tumors (dysgerminoma and gonadoblastoma). Pathogenesis of PGD, neoplastic transformation and therapeutic approach in females with NBS are discussed. [ABSTRACT FROM AUTHOR]

Sexual reversal syndrome is a kind of hereditary disease whose chromosome sex is not consistent with gonad sex. The incidence is very low, and pathogenesis is unknown. The related clinical manifestations are different. This paper report a patient with 46, XY chromosome karyotype, but her gender, internal and external genitalia are female, and the right ovary is accompanied by gonadoblastoma and dysgerminoma, in order to provide some new clinical ideas for the diagnosis, treatment and research of sex reversal syndrome. [ABSTRACT FROM AUTHOR]

Mulheres com cariótipo XY e gônadas em fita são consideradas portadoras de disgenesia gonadal. Essas pacientes apresentam um risco mais alto de desenvolver doenças nas gônadas. Em tais casos, a remoção cirúrgica profilática é indicada. Este artigo relata o caso de uma paciente com disgenesia, apresentando cariótipo 45,X/46,XY. Foi realizada ressecção profilática das gônadas através de laparoscopia. A laparoscopia tem um papel importante na exploração de estruturas pélvicas e permite o diagnóstico, o prognóstico e o tratamento de lesões. Além disso, oferece um método efetivo para a gonadectomia. A remoção profilática das gônadas disgenéticas utilizando essa técnica cirúrgica tem sido preferida em pacientes selecionados.

Background: Mixed gonadal dysgenesis is a rare congenital and challenging condition, characterized mainly by 45,X/46,XY karyotype mosaicism, asymmetrical gonadal development and various internal and external genital anatomy. Because of frequent disorder of genital development and a higher risk of germ cell neoplasia, management of these patients is complex and requires multidisciplinary approach. Case: We present a 45,X/46,XY mixed gonadal dysgenesis patient diagnosed with gonadoblastoma in both gonads after bilateral gonadectomy at 1 year of age. Conclusions: Because of high risk for malignant transformation, gonadectomy of a streak-like gonad and biopsy with orchidopexy or gonadectomy of a dysgenetic testicle is recommended at an early age.

Mixed gonadal dysgenesis (MGD) is a disorder of sex development caused by mosaicism of the Y chromosome, represented by 45,X/46,XY. Prophylactic gonadectomy is recommended as soon as possible after its diagnosis, owing to a high risk of malignancy. In the present case, a 21-year-old woman presented with primary amenorrhea. Although the patient's external genitalia were female, the patient exhibited a hypoplastic uterus, wherein the ovaries were difficult to identify. The patient's height was 146 cm; they had cubitus valgus and webbing of the neck, leading to the consideration of a disorder of sex development. Chromosomal examination revealed 45,X/46,XY mosaicism. Thus, the patient was diagnosed with MGD. After thorough counseling, laparoscopic bilateral gonadectomy was performed. Pathological examination revealed a gonadoblastoma of the left gonad. Postoperatively, the patient had no recurrence and continued on Kaufmann therapy. In conclusion, prophylactic gonadectomy is recommended immediately following a diagnosis of MGD; however, the timing of the surgery should be carefully considered and adequate counseling should be conducted by a multidisciplinary team., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Uyama et al.)

Patients with Swyer syndrome, “XY gonadal dysgenesis”, have fibrosed gonads with a significant risk of developing germ cell tumours. During radiological assessment, a 17-year-old female with Swyer syndrome showed mildly enlarged gonads that were removed laparoscopically and proved pathologically to be bilateral gonadoblastomas. In addition, the right sided lesion showed overgrowth by dysgerminoma. The patient was further treated with combination chemotherapy and she was in complete remission for three years. [ABSTRACT FROM AUTHOR]

Introduction: Germ Cell Tumours (GCT) are heterogenous tumours believed to arise from primordial germ cells. GCT predominantly affects gonads (testis and ovary) and also involves extragonadal sites, characteristically locations along midline of the body. GCT of testis, ovary and extragonadal sites show peculiar histomorphological features and types subject to the age and site of patient. Definite histopathological typing of GCT is of vital importance to decide the further treatment. Till now, very few studies have been conducted in India on GCT of gonads and extragonadal sites. Aim: To study the pathologic findings of GCT including macroscopic and microscopic features and to classify the tumours according to latest World Health Organisation (WHO) classification of GCT for designated site of origin. Materials and Methods: Retrospective analysis was conducted including 141 cases of GCT of all sites, diagnosed at a tertiary cancer center in Udaipur, Rajasthan, India between January 2016 to April 2021. Data were collected regarding demographic, clinical, gross and histopathological details. Results were analysed using Statistical Package of Social Sciences (SPSS) software Version 21.0. method. Results: Germinal cell tumours shows various age ranges for different site of origin. Ovarian GCT age varies from seven years to 65 years. Age group of testicular GCT varies form one to 55 years. Extragonadal GCT (EG GCT) was seen as early as in four-day-old newborn. Out of 141 cases, 103 were ovarian, 21 were testicular and 17 were EG GCT cases. Most common ovarian GCT is Mature Teratoma (MT) (85 cases, 82.53%) and most common malignant ovarian GCT is dysgerminoma (nine cases, 8.74%). Most common testicular GCT type is Malignant Mixed GCT (MM GCT) (nine cases, 42.86%) followed by seminoma (5 cases, 23.81%) and Yolk Sac Tumours (YST) (3 cases, 14.29%). EG GCT involves retroperitoneum (5 cases, 29.41%), anterior mediastinum (4 cases, 23.53%), Sacrococcyx (3 cases, 17.65%) and Central Nervous System (CNS) (2 cases, 11.76%) with most common EG GCT is teratoma (nine cases, 52.94%) Conclusion: Gonadal and extragonadal GCT share many common tumours, albeit, distinctive site-specific histopathological findings also present. These features often complicate the definitive diagnosis of GCT for pathologists, specifically in cases of MM GCT. [ABSTRACT FROM AUTHOR]

Introduction: Germ Cell Tumours (GCT) are heterogenous tumours believed to arise from primordial germ cells. The GCT predominantly affects gonads (testis and ovary) and also involves extragonadal sites, characteristically locations along midline of the body. The GCT of testis, ovary and extragonadal sites show peculiar histomorphological features and types subject to the age and site of patient. Definite histopathological typing of GCT is of vital importance to decide the further treatment. Till now, very few studies have been conducted in India on GCT of gonads and extragonadal sites. Aim: To study the pathologic findings of GCT including macroscopic and microscopic features and to classify the tumours according to latest World Health Organisation (WHO) classification of GCT for designated site of origin. Materials and Methods: Retrospective analysis was conducted including 141 cases of GCT of all sites, diagnosed at a tertiary cancer centre in Udaipur, Rajasthan, India between January 2016 to April 2021. Data were collected regarding demographic, clinical, gross and histopathological details. Results were analysed using Statistical Package of Social Sciences (SPSS) software Version 21.0. method. Results: Germinal cell tumours shows various age ranges for different site of origin. Ovarian GCT age varies from seven years to 65 years. Age group of testicular GCT varies from 1-55 years. Extragonadal GCT (EG GCT) was seen as early as in four-day-old newborn. Out of 141 cases, 103 were ovarian, 21 were testicular and 17 were EG GCT cases. Most common ovarian GCT is Mature Teratoma (MT) (85 cases, 82.53%) and most common malignant ovarian GCT is dysgerminoma (9 cases, 8.74%). Most common testicular GCT type is Malignant Mixed GCT (MM GCT) (9 cases, 42.86%) followed by seminoma (5 cases, 23.81%) and Yolk Sac Tumours (YST) (3 cases, 14.29%). EG GCT involves retroperitoneum (5 cases, 29.41%), anterior mediastinum (4 cases, 23.53%), Sacrococcyx (3 cases, 17.65%) and Central Nervous System (CNS) (2 cases, 11.76%) with most common EG GCT is teratoma (9 cases, 52.94%) Conclusion: Gonadal and extragonadal GCT share many common tumours, albeit, distinctive site-specific histopathological findings also present. These features often complicate the definitive diagnosis of GCT for pathologists, specifically in cases of MM GCT.

Objective: To evaluate the growth data, gonadal functions and tumour risk in children with 45, X/46, XY mosaicism. Design: We reviewed retrospectively the records of 45 patients with 45, X/46, XY mosaicism or variants presented to our Unit from 1989 to 2019. Results: The age at diagnosis ranged from 0.03 to 17.5 years. Twenty‐eight patients had genital anomaly, 14 patients had female external genitalia and 3 patients had normal male genitalia. Patients showed normal height under 2 years of age. Mean height standard deviation score (HSDS) of 19 patients diagnosed before 2 years of age was −0.9 ± 0.6 and that of 26 patients diagnosed after 2 years of age was −2.6 ± 1.5. Ten patients diagnosed before 2 years of age showed growth deceleration after 2 years of age (HSDS decreasing from −0.6 ± 0.7 to −1.4 ± 0.9). Twenty‐one patients reached adult height (AH). Growth hormone (GH) treatment was initiated in 10 patients. Although AHSDS of GH‐treated patients was significantly greater than their mean HSDS before GH therapy (p =.013), it was not significantly different from AHSDS of the untreated group. Seventeen (37.8%) patients exhibited phenotypical features of Turner syndrome (TS) other than short stature. Two patients with genital anomaly had gonadoblastoma and germ cell neoplasia in situ, and one patient with female external genitalia had gonadoblastoma. Conclusions: GH therapy seems to improve AH of patients. Both patients with genital anomaly and female external genitalia have increased risk of germ cell tumours. [ABSTRACT FROM AUTHOR]

Gonadoblastomas are unusual gonadal neoplasias that frequently appear in dysgenetic gonads. Approximately 80% of patients are phenotypic females and 20% are males. A very high frequency is associated with malignant germ cell tumor. We present a case of 37-year-old normal fertile man with descended testis who presented with swelling and pain in left testis since 6 months. On examination, left testis was swollen, hard, and tender. Ultrasound examination of left testis showed hypoechoic lesion neoplastic with multiple enlarged lymph nodes in pre- and para-aortic region. After high left inguinal orchidectomy, histopathology of specimen showed tumor tissue composed of cells arranged in large nests separated by fibrous stroma infiltrated by lymphocytes with focal area showing nests of cells with vesicular nucleus and moderate amount of eosinophilic cytoplasm with eosinophilic material which was calcified, suggestive of seminoma testis with focal area of gonadoblastoma.

Abstract Background Gonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y chromosome. However, this entity in not recognized in the WHO classification of tumours of genital system of domestic animals. Herein, we describe a case of ovarian gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour components, in a phenotypically and cytogenetically normal bitch. Case presentation A 17-year-old cross-breed bitch had a firm, grey-white multinodular mass in the left ovary. The tumour was submitted to histopathological examination and Y chromosome detected through karyotype analysis and PCR studies. Microscopically, the ovary was almost replaced by an irregular neoplasm composed of three distinct, intermixed elements: dysgerminoma, mixed germ cell-sex cord-stromal tumour resembling human GB and a proliferative sex cord-stromal tumour component. The germ cells of gonadoblastoma and dysgerminoma components were immunoreactive for c-KIT. Sex cord-stromal cells of gonadoblastoma were immunoreactive for α-inhibin. The sex cord-stromal tumour was immunoreactive for AE1/AE3, occasionally for α-inhibin and negative for epithelial membrane antigen (EMA). The karyotype was 78, XX and PCR analysis confirmed the absence of the Y chromosome. Conclusion Based on these findings, a diagnosis of gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour was made. This is the first case of ovarian gonadoblastoma in a female dog.

Abstract Background The aim of this study was to review the growth data, gonadal function and tumour risk of children and adolescents with 45,X/46,XY mosaicism who presented to a single centre in China. Methods We conducted a retrospective review of the records of 32 patients with 45,X/46,XY mosaicism or variants who were hospitalized from August 2005 to September 2018. The main outcomes measured were growth data, genital phenotype, gonadal function, gonadal position, and histological results. Results A total of 32 patients were included. The age at diagnosis ranged from 0.6 to 16.3 years. Nineteen patients exhibited ambiguous genitalia, 12 had short stature, and 1 showed a lack of breast development. Seventeen patients were raised as males, and 15 were raised as females. The external masculinisation score (EMS) of patients raised as male was 4.5 (1~12) [median (range)]. The EMS of the females was 0 (0~1.5) [median (range)]. Patients showed normal heights under 2 years old, with a height SDS of 0 (− 1.5~1.4) [median (range)]. Growth appeared to decelerate after age 2 years, with SDS decreased to − 2.8 (− 3.0~ − 0.9) [median (range)]. The percentage of short stature was higher in females than in males (76.9% vs 50.0%). Twenty-five patients had gonadal pathological results. Complete gonadal dysgenesis (CGD) and mixed gonadal dysgenesis (MGD) were the most common pathogenic subtypes, accounting for 48.0 and 36.0%, respectively. Ovotesticular tissue was observed in only 4.0% of patients. Gonadoblastoma and positive OCT3/4 results were found in 18.8% of gonads in children over 2 years of age. Palpable gonads accounted for 50% of these. All patients who had gonadoblastoma were raised as females. Conclusions Patients with 45,X/46,XY might have normal heights until 2 years old. Growth decelerations after 2 years of age were common. Patients who are being raised as females seemed to be shorter than males. CGD and MGD were the most common gonadal pathogenic subtypes. The tumour risk is high in these patients, even in palpable gonads and female patients.

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Objective: The objective of this study is to investigate clinical characteristics and treatment outcomes of patients with disorder of sexual development (DSD) who underwent gonadectomy at a single tertiary center. Materials and Methods: We retrospectively enrolled patients with DSD who received gonadectomies in our hospital from 2000 to 2015. The clinical presentations, laboratory tests, image studies, operative findings, and pathology reports were collected by reviewing medical records. Results: A total of 18 patients with DSD were analyzed, including 17 46XY karyotype and one 45X/46XY karyotype. Among them, 17 patients were assigned female gender. The most common diagnoses were androgen insensitive syndrome (n = 5), 46XY gonad dysgenesis (n = 5), and 17α-hydroxylase deficiency (n = 3). Initial presentations included amenorrhea (n = 9), ambiguous genitalia (n = 5), and abnormal prenatal screening (n = 3). The peak age of gonadectomies was 5 at infantile (1–2 years) and 7 at adolescent period (11–15 years). A total of 19 gonadectomies were performed without complications; pure inguinal approach in 6, inguinal plus laparoscopy exploration in 13. There were no malignancies in all resected gonads; in addition, spermatogenesis was found in only one resected gonad. Conclusions: Female gender assignment was more frequently chosen in our series. The presentations and diagnoses in children with DSD were various; it is important to select individualized treatment strategy for these patients.

46XY pure gonadal dysgenesis (Swyer syndrome) is a rare disorder of sexual development. Patients have a 46XY karyotype, though phenotypically they appear female with normal external genitalia and vagina. Although patients exhibit normal Müllerian structures (uterus, fallopian tubes, and vagina), they possess a pair of bilateral undifferentiated gonad streaks. Delayed puberty and primary amenorrhea are the common presentations. There is an increased risk of developing tumors in the gonads and therefore a bilateral gonadectomy is recommended. A 16-year-old girl who presented with primary amenorrhea was diagnosed with Swyer syndrome. She underwent prophylactic bilateral gonadectomy and salpingectomies. She was discovered to have no gonadal malignancy, conversely dysgerminoma solely within the fallopian tube. Both bilateral salpingectomies and bilateral gonadectomies should be recommended as the operation of choice in patients with Swyer Syndrome. [ABSTRACT FROM AUTHOR]

Swyer syndrome is a difference of sex development that is typically associated with mutations in genes responsible for testicular development. It is speculated that some cases may result from cryptic 45,X/46,XY mosaicism leading to abnormal gonadal development. The presence or absence of a 45,X lineage is important for prognosis and management. We present a case of apparent Swyer syndrome associated with a 46,XY chromosomal complement in lymphocytes and 45,X/46,XY mosaicism on analysis of her noncancerous gonad. Gonadal histology was consistent with a 45,X phenotype. This case demonstrates the clinical variability in the presentation of 45,X/46,XY mosaicism and highlights the importance of thorough genetic testing that includes consideration of chromosomal mosaicism. We will discuss the implications of this diagnosis for management. [ABSTRACT FROM AUTHOR]