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.

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.

OBJECTIVE: 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.
METHODS: 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.
CONCLUSIONS: 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.

BACKGROUND: 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.
METHODS: We present 2 rare cases of 46, XY DSD, specifically XY pure gonadal dysgenesis and complete androgen insensitivity syndrome.
RESULTS: 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.
CONCLUSIONS: Laparoscopic bilateral prophylactic gonadectomy and long-term hormone therapy with patient counseling and support are recommended.

OBJECTIVE: To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma.
METHODS: Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed.
RESULTS: Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence.
CONCLUSIONS: Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

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.

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.

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).

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.

BACKGROUND: 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.
CONCLUSIONS: 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.