Review

Authors: Y F Lau

Topics: Animals; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Conserved Sequence; Cyclin B; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Gonadoblastoma; Histone Chaperones; Humans; Male; Nuclear Proteins; Prostatic Neoplasms; Proteins; Sex-Determining Region Y Protein; Testicular Neoplasms; Transcription Factors; Y Chromosome

PubMed: 10090875
DOI: 10.1086/302353

Authors: Mauri José Piazza, Almir Antonio Urbanetz

This review describes the germ cell neoplasms that are malignant and most commonly associated with several types of gonadal dysgenesis. The most common neoplasm is gonadoblastoma, while others including dysgerminomas, yolk-sac tumors and teratomas are rare but can occur. The purpose of this review is to evaluate the incidences of these abnormalities and the circumstances surrounding these specific tumors.According to well-established methods, a PubMed systematic review was performed, to obtain relevant studies published in English and select those with the highest-quality data.Initially, the first search was performed using gonadal dysgenesis as the search term, resulting in 12,887 PubMed papers, published, from 1945 to 2017. A second search using ovarian germ cell tumors as the search term resulted in 10,473 papers, published from 1960 to 2017. Another search was performed in Medline, using germ cell neoplasia as the search term, and this search resulted in 7,560 papers that were published between 2003 to 2016, with 245 new papers assessing gonadoblastomas.The higher incidence of germ cell tumors in gonadal dysgenesis is associated with a chromosomal anomaly that leads to the absence of germ cells in these gonads and, consequently, a higher incidence of neoplasms when these tumors are located inside the abdomen. Several hypotheses suggest that increased incidence of germ cell tumors involves all or part of the Y chromosome or different genes.

Topics: Female; Gonadal Dysgenesis; Humans; Incidence; Male; Neoplasms, Germ Cell and Embryonal; Risk Factors

PubMed: 31721911
DOI: 10.6061/clinics/2019/e408

Review

Authors: N Bouayed Abdelmoula, A Amouri

Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

Topics: Chromosomes, Human, Y; Genotype; Humans; Karyotyping; Male; Phenotype; Sex Chromosome Aberrations

PubMed: 16061435
DOI: No ID Found

Review

Authors: Wei Shen, Ya Li

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.

Topics: Female; Humans; Turner Syndrome; Gonadoblastoma; Quality of Life; Puberty; Ovarian Neoplasms; Estrogens

PubMed: 37822273
DOI: 10.1002/mgg3.2300

Authors: Tengge Yu, Li Liu

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.

CONCLUSION

Laparoscopic bilateral prophylactic gonadectomy and long-term hormone therapy with patient counseling and support are recommended.

Topics: Humans; Androgen-Insensitivity Syndrome; Gonadal Dysgenesis, 46,XY; Gonadoblastoma

PubMed: 38905377
DOI: 10.1097/MD.0000000000038297

Authors: Tazim Dowlut-McElroy, Veronica Gomez-Lobo

Topics: Castration; Chromosomes, Human, Y; Female; Fertility; Gonadoblastoma; Humans; Mosaicism; Ovarian Neoplasms; Turner Syndrome

PubMed: 35358708
DOI: 10.1016/j.jpag.2022.03.003

Review

Authors: Martin Kathrins, Thomas F Kolon

Disorders of sex development (DSD) represent a spectrum of conditions in which chromosomal, gonadal, or anatomic sex are atypical and affect 1 in 4,500-5,000 live births. The diagnosis of DSD raises concerns of tumor risk and treatment as well as future fertility preservation. We review the current understanding of the types of gonadal tumors that arise in DSD patients as well as possible markers and treatment. The goal is to inform the members of the DSD team (urologist, endocrinologist, geneticist, psychologist) of the latest findings regarding malignancy in DSD. PubMed and Google Scholar literature searches were performed of current and past peer-reviewed literature on DSD (intersex) regarding gonadal development and tumor formation/treatment. Relevant reviews and original research articles were examined, including cited references, and a synopsis of the data was generated. DSD patients are at increased risk for the development of testicular carcinoma in-situ (CIS) and germ cell tumors (GCT), including seminoma, non-seminoma, juvenile granulosa cell, gonadoblastoma, and dysgerminoma. Cancer risk factors include Y-chromosomal material and gonadal position, especially for streak gonads. The 46 XX DSD patients [congenital adrenal hyperplasia (CAH)] with no genetic Y-chromosomal material are not at higher risk of cancer. Post-pubertal complete androgen insensitivity syndrome (AIS) patients remain prone to tumor development if the testes remain in the abdomen. Estimates of the risk of GCT in partial AIS for untreated undescended testes may be as high as 50%. The cancer risk of scrotal testes in partial AIS is unknown. CIS occurs almost exclusively in patients with hypovirilization, most notably in AIS. Persistent Mullerian Duct Syndrome (PMDS) confers the usual cancer risk associated with cryptorchidism, but also a possible tumor risk of the Mullerian remnant. Several markers are under investigation for tumor evaluation in the DSD population beyond hCG and AFP (Oct3/4, TSPY, WT-1). The management of patients with DSD is complex and evaluation of tumor risk is aided by advances in genotyping for Y-chromosomal material not evident in traditional karyotyping. More complete genetic screening for DSD patients should increasingly become the standard of care. Developments in pathologic diagnosis will further challenge our traditional understanding of the oncologic management and surveillance of these patients. Future studies utilizing more advanced histologic examination of gonads will improve our understanding of the true incidences of malignancy in this diverse population.

PubMed: 27785439
DOI: 10.21037/tau.2016.08.09