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Translational Andrology and Urology Oct 2016Disorders 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... (Review)
Review
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 -
Asian Journal of Andrology 2015Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from... (Review)
Review
Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition) with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT), such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.
Topics: Azoospermia; Cell Cycle Proteins; Chromosomes, Human, Y; Gene Expression Regulation, Neoplastic; Genes, Y-Linked; Humans; Male; Neoplasms; Neoplasms, Germ Cell and Embryonal; Nuclear Proteins; RNA-Binding Proteins
PubMed: 25814157
DOI: 10.4103/1008-682X.150842 -
Revista Paulista de Pediatria : Orgao... 2016To assess the prevalence of Y-chromosome sequences and gonadoblastoma in patients with Turner syndrome (TS) using molecular techniques. (Review)
Review
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 and ; (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.
Topics: Chromosomes, Human, Y; Female; Gonadoblastoma; Humans; Karyotyping; Ovarian Neoplasms; Sequence Analysis, DNA; Turner Syndrome
PubMed: 26525685
DOI: 10.1016/j.rpped.2015.06.007 -
Pediatric Endocrinology, Diabetes, and... 2017Turner syndrome (TS) is an inherited genetic disorder caused by numerical and/or structural chromosome X aberrations occurring at a frequency of 1:1200-1:2500 live-born... (Review)
Review
Turner syndrome (TS) is an inherited genetic disorder caused by numerical and/or structural chromosome X aberrations occurring at a frequency of 1:1200-1:2500 live-born girls. The most common karyotype is X chromosome monosomy (45,X) (approximately 50-60% of cases). Approximately 5-6% of patients may have abnormal Y chromosome or mosaicism characterized by the coexistence of 45,X cell line with cell line in which all or part of chromosome Y is present. In patients with TS who have all or fragmented genetic material from chromosome Y there is a substantial risk of cancerous lesions in these dysgenetic gonads. This paper stands for the review of the current knowledge on the genetic material of the Y chromosome in TS, especially in view of the risk of developing malignancies such as gonadoblastoma and dysgerminoma.
Topics: Chromosomes, Human, Y; Female; Gonadoblastoma; Humans; Mosaicism; Mutation; Ovarian Neoplasms; Turner Syndrome
PubMed: 29073306
DOI: 10.18544/PEDM-23.01.0072 -
Translational Andrology and Urology Oct 2020Differences of sexual development (DSD) are known to be associated with an elevated risk of malignant and pre-malignant tumors. However, given the rarity of DSD and... (Review)
Review
Differences of sexual development (DSD) are known to be associated with an elevated risk of malignant and pre-malignant tumors. However, given the rarity of DSD and tumors in patients with DSD, more robust, large scale, prospective literature is required to truly determine the extent of this association, long-term outcomes and the nuances associated with the wide variety of DSD diagnoses. In addition, the spectrum of diagnoses and nomenclature has been ever-changing, limiting assessment of long-term patient outcomes. This review aims to provide an overview of the pathogenesis of DSD conditions, potential malignancies associated with the diagnoses, the available screening for malignancy, and the most recent data on stratification for each DSD diagnosis and association with malignancy.
PubMed: 33209714
DOI: 10.21037/tau-19-726 -
Journal of Clinical Pathology Sep 1992Most patients with gonadoblastoma have dysgenetic gonads. This rare tumour has been described in three pregnant women. A fourth case in a 26 year old pregnant woman who...
Most patients with gonadoblastoma have dysgenetic gonads. This rare tumour has been described in three pregnant women. A fourth case in a 26 year old pregnant woman who presented with gonadoblastoma and dysgerminoma, is reported. She had a normal term pregnancy, 46XX chromosomes, normal genitalia, no history of menstrual irregularities and no signs of hyperandrogenism, thereby differing from the other reported cases. The germ cell component of this patient's tumour had undergone rapid overgrowth, most of the tumour comprising pure dysgerminoma. It is suggested that gonadoblastoma may occur in functionally and morphologically normal gonads more often than previous case reports imply.
Topics: Adult; Dysgerminoma; Female; Fertility; Humans; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 1401220
DOI: 10.1136/jcp.45.9.828