-
Klinicka Onkologie : Casopis Ceske a... 2019Ovarian tumors in childhood and adolescence are distinguished from those that arise in adulthood by their histological subtype. These tumors may arise as the first...
BACKGROUND
Ovarian tumors in childhood and adolescence are distinguished from those that arise in adulthood by their histological subtype. These tumors may arise as the first manifestation of a cancer predisposition syndrome. Correct diagnosis of the syndrome may offer the possibility of surveillance for other members of the patients family.
PURPOSE
To summarize current knowledge about paediatric ovarian tumors that may be associated with genetically defined cancer syndromes. Juvenile granulosa cell tumors occur in those with Ollier disease and Maffucci syndrome; they are caused by postzygotic IDH1 and IDH2 gene mutations. Sertoli-Leydig cell tumors usually arise in association with DICER1 syndrome, which is caused by germline DICER1 gene mutations. Sex cord tumors with annular tubules and Sertoli cell tumors may arise in patients with Peutz-Jeghers syndrome; this syndrome is caused by germline STK11 gene mutations. The majority of germ cell tumors develop in the context of gonadal dysgenesis. In XY gonadal dysgenesis, the presence of a Y chromosome material renders the patient at increased risk for developing gonadal malignancy. Characteristically, these patients develop gonadoblastoma, which has the potential to evolve into dysgerminoma and exhibit malignant behavior. Sex-chromosome aneuploidy syndromes or mutations in genes involved in gonadal development and differentiation may cause gonadal dysgenesis. Small cell carcinoma of the ovary of a hypercalcaemic type is usually caused by loss-of-function mutations in the SMARCA4 gene.
CONCLUSION
Ovarian tumors are uncommon during childhood and adolescence. It is always necessary to consider gonadal dysgenesis or any of the inherited cancer syndromes. These patients require interdisciplinary care, careful noting of personal and family history, precise clinical examination, laboratory testing, and differential diagnosis by a clinician with a good knowledge of genetic syndromes. Expert pathological review may be required for correct diagnoses. This is necessary for appropriate management and to establish an association with hereditary cancer syndromes. The work was supported by the Ministry of Health of the Czech Republic - Conceptual Development of Research Organization, Faculty Hospital of Ostrava /2015. We thank to Lenka Foretová, M.D., Ph.D., (MMCI, Brno) and Radoslava Tomanová, M.D., (Institute of Pathology, University Hospital Ostrava) for rewarding advice, Mrs. Jana Němcová (Department of Medical Genetics, University Hospital Ostrava), Bc. Ludmila Stuchlá and Mrs. Lenka Zivčáková (Medical Library, University Hospital Ostrava) for help during manuscript preparation. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 10. 3. 2019 Accepted: 16. 4. 2019.
Topics: Adolescent; Child; Female; Genetic Predisposition to Disease; Humans; Neoplastic Syndromes, Hereditary; Ovarian Neoplasms
PubMed: 31409083
DOI: 10.14735/amko2019S79 -
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 -
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 -
Molecular and Clinical Oncology Aug 2016Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls...
Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma.
PubMed: 27446585
DOI: 10.3892/mco.2016.915 -
Pediatric and Developmental Pathology :... 2015Ullrich-Turner syndrome (UTS) is a common chromosomal abnormality caused by partial or complete X chromosome monosomy. One half of the patients have a 45,X karyotype,...
Ullrich-Turner syndrome (UTS) is a common chromosomal abnormality caused by partial or complete X chromosome monosomy. One half of the patients have a 45,X karyotype, whereas the remaining patients display other X chromosome anomalies. In 6% to 11% of UTS, a normal or partly deleted Y chromosome has been found. A 10% to 30% risk of developing gonadoblastoma was found in the latter patients. The aim of this study was to evaluate the prevalence of Y chromosome-derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplasms in patients with UTS. Of 217 patients studied with UTS and chromosome analysis of peripheral-blood lymphocytes, Y chromosome material was found in 20 patients. Fluorescence in situ hybridization (FISH) testing was performed to characterize the structurally abnormal Y chromosome in 13 cases. Molecular analysis of the SRY gene could only be performed in 20 patients with 45,X karyotype. Two patients had the SRY genomes. Of the 20 patients with Y chromosome-derived material, 17 underwent gonadectomy. The incidence of gonadoblastoma development in our series was 35.5%. Furthermore, 1 patient also showed a pure dysgerminoma, and another showed a mixed dysgerminoma and embryonal carcinoma. We emphasize the importance of complete processing of the gonadectomy specimen, including step sections, molecular studies, and FISH, in addition to the classic cytogenetic searching for Y chromosome sequences, in patients who present with a nonmosaic 45,X karyotype. Finally, we propose to routinely collect a sample for storage in the tumor bank for future studies.
Topics: Adolescent; Argentina; Child; Child, Preschool; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Genetic Predisposition to Disease; Gonadoblastoma; Humans; In Situ Hybridization, Fluorescence; Incidence; Karyotype; Karyotyping; Mosaicism; Ovarian Neoplasms; Phenotype; Sex-Determining Region Y Protein; Treatment Outcome; Turner Syndrome
PubMed: 25535833
DOI: 10.2350/14-08-1539-OA.1 -
Journal of Obstetrics and Gynaecology :... May 2016A retrospective study was conducted to review incidence, clinical practice, surgical management and histology of adolescent ovarian masses in order to audit and improve...
A retrospective study was conducted to review incidence, clinical practice, surgical management and histology of adolescent ovarian masses in order to audit and improve future practices. Complete hospital records of all adolescents between 10 and 20 years who had undergone surgery for ovarian masses were analysed between November 2006 to 2014. Parameters analysed were age, clinical features, diagnosis, operative procedure and histopathology. Ninety-four patients were included in the study and among them, 37 had non-neoplastic masses, 30 had benign neoplasms while 27 had malignant tumors. The main clinical presentations were abdominal pain (54%) and abdominal mass (41%). Dermoid was the most common benign neoplasm while germ cell tumor was the most common malignant mass; dysgerminoma being the commonest (68%). Malignancy was more common in early adolescence (12 ± 4.8 years) while non-neoplastic masses were seen more frequently in late adolescence (17.7 ± 2.2 years). There was a fair correlation between ultrasound and histopathological diagnosis.
Topics: Adolescent; Child; Dermoid Cyst; Dysgerminoma; Female; Gynecologic Surgical Procedures; Hospitals; Humans; Ovarian Cysts; Ovarian Neoplasms; Retrospective Studies; Young Adult
PubMed: 26789784
DOI: 10.3109/01443615.2015.1103721 -
Clinics (Sao Paulo, Brazil) 2019This review describes the germ cell neoplasms that are malignant and most commonly associated with several types of gonadal dysgenesis. The most common neoplasm is...
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 -
BMC Cancer Nov 2020Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM...
BACKGROUND
Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma.
METHODS
Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient.
RESULTS
This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient's bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma.
CONCLUSIONS
These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.
Topics: Dysgerminoma; Female; Humans; Mastocytosis, Systemic; Middle Aged; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms
PubMed: 33246418
DOI: 10.1186/s12885-020-07653-z -
Journal of Reproductive Immunology Feb 2024Seminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment....
BACKGROUND
Seminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment. According to the failure of conventional treatments in some patients, it is crucial to identify novel prognostic and therapeutic biomarkers for these patients. The objectives of this study were to evaluate the expression of CD45RO and PD-1/PD-L1 and investigate their association with the clinicopathological characteristics of the patients.
METHODS
Immunohistochemistry was performed to assess the expression of CD45RO, PD-1, and PD-L1 in tumor-infiltrated lymphocytes (TILs), and tumor cells in 33 seminoma and 31 dysgerminoma patients. The expression levels were evaluated using a semiquantitative approach, weighted histoscore, which considers both the intensity and extent of staining.
RESULTS
All seminoma and dysgerminoma patients exhibited CD45RO expression in TILs, with 66.7 % and 90.3 % displaying high levels of expression, respectively. PD-1 expression in TILs was observed at low levels in 81.8 % and 77.4 % and at high levels in 18.2 % and 19.4 % of seminoma and dysgerminoma patients, respectively. Likewise, low expression of PD-L1 in tumor cells was detected in 63.6 % of seminoma and 61.3 % of dysgerminoma patients, while none of the patients exhibited high expression of PD-L1. In seminoma patients, a positive correlation was observed between PD-1 expression in TILs and CD45RO expression and between PD-L1 expression in tumor cells and TILs score.
CONCLUSION
The frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.
Topics: Female; Humans; Male; B7-H1 Antigen; Dysgerminoma; Memory T Cells; Prognosis; Programmed Cell Death 1 Receptor; Seminoma; Testicular Neoplasms; Tumor Microenvironment; Leukocyte Common Antigens
PubMed: 38171036
DOI: 10.1016/j.jri.2023.104184 -
Gynecologic Oncology Mar 2023We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and...
OBJECTIVE
We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and assessed it in female patients with germ cell tumors (GCTs). We sought to validate these modified IGCCCG (mIGCCCG) models in a new cohort.
METHODS
We queried institutional databases for female patients with GCTs treated at Memorial Sloan Kettering Cancer Center from 1/1/1990-6/1/2020. The mIGCCCG model classifies patients with non-dysgerminomas as good, intermediate, or poor risk based on tumor markers using male IGCCCG cutoffs and absence/presence of non-pulmonary/peritoneal visceral metastasis. In dysgerminomas, good- and intermediate-risk groups are defined by absence/presence of non-pulmonary/peritoneal visceral metastasis. Progression-free survival (PFS) and overall survival (OS) were estimated for each group in the validation and combined original and validation cohorts. Associations between individual clinical factors and outcomes were evaluated.
RESULTS
Among 183 female patients with GCTs, clinical characteristics and outcomes were similar between the original (n = 93) and validation (n = 90) cohorts. In multivariable models, higher stage, older age, and non-dysgerminoma histology predicted worse PFS and OS (p < 0.05). Among 162 patients who received chemotherapy, preoperative and pre-chemotherapy mIGCCCG models were significantly associated with PFS and OS (p < 0.001 for all groups). With the preoperative model, 3-year PFS rates were 94%, 76%, and 50% in the good-, intermediate-, and poor-risk patients, respectively; OS rates were 96%, 86%, and 52%, respectively. Even within stage groups, mIGCCCG risk classifications were associated with clinical outcomes.
CONCLUSIONS
A female-specific mIGCCCG risk model effectively stratifies patients and should be incorporated into clinical trials.
Topics: Humans; Male; Female; Prognosis; Neoplasms, Germ Cell and Embryonal; Progression-Free Survival; Biomarkers, Tumor; Dysgerminoma; Ovarian Neoplasms; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36669327
DOI: 10.1016/j.ygyno.2022.12.022