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Journal of Ovarian Research Sep 2019Gonadoblastoma (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...
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.
Topics: Adult; Animals; Cell Proliferation; Dog Diseases; Dogs; Dysgerminoma; Female; Gonadoblastoma; Humans; Karyotype; Ovarian Neoplasms; Ovary; Phenotype; Proto-Oncogene Proteins c-kit; Sex Cord-Gonadal Stromal Tumors; Stromal Cells; Y Chromosome
PubMed: 31547830
DOI: 10.1186/s13048-019-0561-x -
Human Pathology Jul 2017Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2% to 5% of cases. Both genetic and... (Comparative Study)
Comparative Study Review
Perspectives on testicular sex cord-stromal tumors and those composed of both germ cells and sex cord-stromal derivatives with a comparison to corresponding ovarian neoplasms.
Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2% to 5% of cases. Both genetic and epigenetic factors account for the differences in frequency and histologic composition between testicular and ovarian SCSTs. For example, large cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing Sertoli cell neoplasia occur in the testis but have not been described in the ovary. In this article, we discuss recently described diagnostic entities as well as inconsistencies in nomenclature used in the recent World Health Organization classifications of SCSTs in the testis and ovary. We also thoroughly review the topic of neoplasms composed of both germ cells and sex cord derivatives with an emphasis on controversial aspects. These include "dissecting gonadoblastoma" and testicular mixed germ cell-sex cord stromal tumor (MGC-SCST). The former is a recently described variant of gonadoblastoma that sometimes is an immediate precursor of germinoma in the dysgenetic gonads of patients with a disorder of sex development. Although the relationship of dissecting gonadoblastoma to the previously described undifferentiated gonadal tissue is complex and not entirely resolved, we believe that it is preferable to continue to use the term undifferentiated gonadal tissue for those cases that are not neoplastic and are considered to be the precursor of classical gonadoblastoma. Although the existence of testicular MGC-SCST has been challenged, the most recent evidence supports its existence; however, testicular MGC-SCST differs significantly from ovarian examples due to both genetic and epigenetic factors.
Topics: Biomarkers, Tumor; Cell Differentiation; Cell Lineage; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Male; Neoplasms, Complex and Mixed; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Phenotype; Sex Cord-Gonadal Stromal Tumors; Testicular Neoplasms
PubMed: 28445692
DOI: 10.1016/j.humpath.2017.04.009 -
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 -
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 -
Diagnostic and Interventional Radiology... Jan 2023Ovarian dysgerminoma (OD) is a rare germ cell tumor accounting for 1%-2% of all malignant ovarian tumors and is generally associated with a good prognosis. The condition...
Ovarian dysgerminoma (OD) is a rare germ cell tumor accounting for 1%-2% of all malignant ovarian tumors and is generally associated with a good prognosis. The condition is more frequent in young women and can arise in dysgenetic gonads that contain gonadoblastomas. While the definitive diagnosis of OD is only possible histologically, certain radiological features can provide facilitating clues. A large, unilateral, solid, lobulated ovarian tumor with markedly enhancing septa should raise the suspicion of OD in young women. Serum lactate dehydrogenase is characteristically elevated in this tumor type and can complement its diagnosis and postoperative follow-up; however, it is a nonspecific marker. Moreover, knowing the mimickers of OD is essential to optimizing the radiological image interpretation and allowing for adequate management and timely treatment. Therefore, in this article, the radiological and clinical-pathologic features of ODs were reviewed to allow radiologists to become familiarized with them and narrow the diagnostic possibilities when facing this type of tumor.
Topics: Female; Humans; Dysgerminoma; Ovarian Neoplasms; Neoplasms, Germ Cell and Embryonal; Radiography
PubMed: 36959710
DOI: 10.5152/dir.2022.21317 -
Gonadectomy in Individuals with Turner Syndrome and Y Chromosome Material: Fertility Considerations.Journal of Pediatric and Adolescent... Aug 2022
Topics: Castration; Chromosomes, Human, Y; Female; Fertility; Gonadoblastoma; Humans; Mosaicism; Ovarian Neoplasms; Turner Syndrome
PubMed: 35358708
DOI: 10.1016/j.jpag.2022.03.003 -
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 -
Frontiers in Endocrinology 202217α-hydroxylase/17,20-lyase deficiency (17-OHD), caused by mutations in the gene of the cytochrome P450 family 17 subfamily A member 1 (CYP17A1), is a rare type of... (Review)
Review
17α-hydroxylase/17,20-lyase deficiency (17-OHD), caused by mutations in the gene of the cytochrome P450 family 17 subfamily A member 1 (CYP17A1), is a rare type of congenital adrenal hyperplasia (CAH), usually characterized by cortisol and sex steroid deficiency combined with excessive mineralocorticoid. Gonadoblastoma is a relatively rare ovarian tumor that is frequently seen among patients with 46,XY gonadal dysgenesis. Rarely have they been reported in female patients with normal 46,XX karyotype. Here, we report an interesting case of an 11-year-old Chinese girl who presented acute abdominal pain that was later attributed to tumor rupture of right ovarian gonadoblastoma with dysgerminoma. Further evaluations revealed hypertension and hypokalemia. Hormonal findings showed increased progesterone, hypergonadotropic hypogonadism, and low cortisol levels. Her chromosome karyotype was 46,XX without Y chromosome material detected. Genetic analysis revealed that the patient had a homozygous pathogenic variant c.985_987delTACinsAA (p.Y329Kfs*90) in exon 6 of the gene and that her parents were all heterozygous carriers of this pathogenic variant. Due to the variable clinical manifestations of 17-OHD, meticulous assessment including genetic analysis is necessary. Further study is warranted to unravel the mechanism of gonadoblastoma in a patient with normal karyotypes.
Topics: Humans; Female; Child; Dysgerminoma; Mixed Function Oxygenases; Gonadoblastoma; Hydrocortisone; Ovarian Neoplasms; Karyotype; Lyases
PubMed: 36589847
DOI: 10.3389/fendo.2022.989695 -
International Journal of Molecular... Oct 2019The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased... (Review)
Review
The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients.
Topics: Animals; Biomarkers, Tumor; Biopsy; Cell Cycle Proteins; Chromosomes, Human, Y; Developmental Biology; Disorders of Sex Development; Genetic Predisposition to Disease; Germ Cells; Gonadoblastoma; Gonads; Humans; Male; Nanog Homeobox Protein; Neoplasms, Germ Cell and Embryonal; Octamer Transcription Factor-3; Proto-Oncogene Proteins c-kit; Risk Factors; SOXF Transcription Factors; Testicular Neoplasms; Testis
PubMed: 31658757
DOI: 10.3390/ijms20205017 -
Reproduction & Fertility Apr 2021The Ubiquitous Transcribed Y ( a.k.a. ) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, (a.k.a. ), encode a histone lysine...
UNLABELLED
The Ubiquitous Transcribed Y ( a.k.a. ) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, (a.k.a. ), encode a histone lysine demethylase removing chromatin H3K27 methylation marks at genes transcriptional start sites for activation. Both proteins harbour the conserved Jumonji C (JmjC) domain, functional in chromatin metabolism, and an extended N-terminal tetratricopeptide repeat (TPR) block involved in specific protein interactions. Specific antisera for human UTY and UTX proteins were developed to distinguish the expression of both proteins in human germ cells by immunohistochemical experiments on appropriate tissue sections. In the male germ line, UTY was expressed in the fraction of A spermatogonia located at the basal membrane, probably including spermatogonia stem cells. UTX expression was more spread in all spermatogonia and in early spermatids. In female germ line, UTX expression was found in the primordial germ cells of the ovary. UTY was also expressed during fetal male germ cell development, whereas UTX expression was visible only at distinct gestation weeks. Based on these results and the conserved neighboured location of and in Yq11 found in mammals of distinct lineages, we conclude that such as is part of the Azoospermia factor a (AZFa) locus functioning in human spermatogonia to support the balance of their proliferation-differentiation rate before meiosis. Comparable UTY and DDX3Y expression was also found in gonadoblastoma and dysgerminoma cells found in germ cell nests of the dysgenetic gonads of individuals with disorders of sexual development and a Y chromosome in karyotype (DSD-XY). This confirms that AZFa overlaps with GBY the Gonadoblastoma susceptibility Y locus, and includes the gene.
LAY SUMMARY
AZFa Y genes are involved in human male germ cells development and support gonadoblastoma (germ cell tumour precursor cells) in the aberrant germ cells of the gonads of females with genetic disorders of sexual development. The AZFa gene on the male Y chromosome is equivalent to on the female X chromosome. These genes are involved in removing gene regulators to enable activation of other genes (i.e. removal of histone methylation known as epigenetic modifications). We wanted to learn the function of UTY and UTX in developing sperm and eggs in human tissues and developed specific antibodies to detect both proteins made by these genes. Both UTY and UTX proteins were detected in adult and fetal sperm precursor cells (spermatogonia). UTX was detected in egg precursor cells (primordial germ cells). UTY was detected in gonadoblastoma and dysgerminoma tumour cells (germ cell tumours originating from genetic disorders of sexual development due to having a Y chromosome). Based on our study, we conclude that UTY is not only part of AZFa, but also of GBY the overlapping gonadoblastoma susceptibility Y region.
Topics: Adult; Animals; Chromatin; Chromosomes, Human, Y; DEAD-box RNA Helicases; Dysgerminoma; Female; Gonadoblastoma; Histone Demethylases; Humans; Male; Mammals; Minor Histocompatibility Antigens; Neoplasms, Germ Cell and Embryonal; Nuclear Proteins; Ovarian Neoplasms; Semen; Spermatogonia
PubMed: 35128450
DOI: 10.1530/RAF-20-0049