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The Journal of Clinical Endocrinology... Jun 2006The purpose of the study was to define the histological origin of gonadoblastomas, allowing the identification of high-risk patients.
PURPOSE
The purpose of the study was to define the histological origin of gonadoblastomas, allowing the identification of high-risk patients.
EXPERIMENTAL DESIGN
Sixty paraffin-embedded gonadectomy or gonadal biopsy samples of 43 patients with gonadal dysgenesis were selected from our archives. We studied the morphology and immunohistochemical properties of the germ cells in 40 samples without neoplastic transformation and compared these findings with the morphological and immunohistochemical characteristics of 20 samples containing gonadoblastoma/dysgerminoma.
RESULTS
The overall incidence of germ cell tumors in our patient series was 35%. In dysgenetic gonads without germ cell neoplasia, besides the presence of areas with testicular and/or ovarian differentiation, areas of undifferentiated gonadal tissue were identified in 13 of 40 samples (32.5%). A subpopulation of germ cells within these undifferentiated areas stained positive for octamer binding transcription factor (OCT)3/4, the stem cell factor receptor, placental-like alkaline phosphatase, and testis-specific protein-Y encoded. Gonadoblastoma germ cells display identical staining results. Moreover, in gonads containing gonadoblastoma, adjacent to this lesion, areas of undifferentiated gonadal tissue with identical immunohistochemical characteristics were identified in 10 of 20 samples (50%). No adjacent tissue was available in five cases, whereas in the five remaining cases, it consisted of streak tissue. In three cases, an accumulation of OCT3/4-positive germ cells in the proximity of the malignant lesions was found, suggesting clonal expansion and final organization into gonadoblastoma nests.
CONCLUSIONS
Based on these observations, we hypothesize that gonadoblastomas originate from surviving OCT3/4-positive germ cells in areas of undifferentiated gonadal tissue within the dysgenetic gonad. Supportive evidence was obtained that carcinoma in situ arises in regions with testicular differentiation.
Topics: Adolescent; Adult; Alkaline Phosphatase; Carcinoma in Situ; Cell Cycle Proteins; Cell Differentiation; Child; Child, Preschool; Dysgerminoma; Female; Gonadal Dysgenesis; Gonadoblastoma; Humans; Immunohistochemistry; Infant; Isoenzymes; Male; Octamer Transcription Factor-3; Ovarian Neoplasms; Proto-Oncogene Proteins c-kit; Testicular Neoplasms
PubMed: 16608895
DOI: 10.1210/jc.2005-2554 -
Pediatric Blood & Cancer Apr 2018In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with... (Clinical Trial)
Clinical Trial Comparative Study
PURPOSE
In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with normal gonadal development.
PATIENTS AND METHODS
Patients from the Children's Oncology Group AGCT0132 with malignant ovarian GCTs were included. Within this population, we sought to identify patients with gonadoblastoma, streak ovaries, or other evidence of gonadal dysgenesis (GD). Patients with malignant GCTs containing one or more of the following histologies-yolk sac tumor, embryonal carcinoma, or choriocarcinoma-were included. Patients were compared with respect to event-free survival (EFS) and overall survival (OS).
RESULTS
Nine patients with GD, including seven with gonadoblastoma (mean age, 9.3 years), were compared to 100 non-GD patients (mean age, 12.1 years). The estimated 3-year EFS for patients with GD was 66.7% (95% CI 28.2-87.8%) and for non-GD patients was 88.8% (95% CI 80.2-93.8%). The estimated 3-year OS for patients with GD was 87.5% (95% CI 38.7-98.1%) and for non-GD patients was 97.6% (95% CI of 90.6-99.4%).
CONCLUSION
Patients presenting with nongerminomatous malignant ovarian GCTs in the context of GD have a higher rate of events and death than counterparts with normal gonads. These findings emphasize the importance of noting a contralateral streak ovary or gonadoblastoma at histology for any ovarian GCT and support the recommendation for early bilateral gonadectomy in patients known to have GD with Y chromosome material. In contrast to those with pure dysgerminoma, these patients may represent a high-risk group that requires a more aggressive chemotherapy regimen.
Topics: Adolescent; Adult; Child; Child, Preschool; Disease-Free Survival; Female; Gonadal Dysgenesis; Humans; Infant; Infant, Newborn; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Survival Rate
PubMed: 29286555
DOI: 10.1002/pbc.26913 -
Journal of Clinical Research in... Aug 2021We describe a 46,XX girl with Denys-Drash syndrome, showing both kidney disease and genital abnormalities, in whom a misdiagnosis of hyperandrogenism was made. A 15...
We describe a 46,XX girl with Denys-Drash syndrome, showing both kidney disease and genital abnormalities, in whom a misdiagnosis of hyperandrogenism was made. A 15 year-old girl was affected by neonatal nephrotic syndrome, progressing to end stage kidney failure. Hair loss and voice deepening were noted during puberty. Pelvic ultrasound and magnetic resonance imaging showed utero-tubaric agenesis, vaginal atresia and urogenital sinus, with inguinal gonads. Gonadotrophin and estradiol levels were normal, but testosterone was increased up to 285 ng/dL at Tanner stage 3. She underwent prophylactic gonadectomy. Histopathology reported fibrotic ovarian cortex containing numerous follicles in different maturation stages and rudimental remnants of Fallopian tubes. No features of gonadoblastoma were detected. Unexpectedly, testosterone levels were elevated four months after gonadectomy (157 ng/dL). Recent medical history revealed chronic daily comsumption of high dose biotin, as a therapeutic support for hair loss. Laboratory immunoassay instruments used streptavidin-biotin interaction to detect hormones and, in competitive immunoassays, high concentrations of biotin can result in false high results. Total testosterone, measured using liquid chromatography tandem mass spectrometry, was within reference intervals. Similar testosterone levels were detected on repeat immunoassay two weeks after biotin uptake interruption. Discordance between clinical presentation and biochemical results in patients taking biotin, should raise the suspicion of erroneous results. Improved communication among patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays.
Topics: Adolescent; Biotin; Castration; Denys-Drash Syndrome; Diagnostic Errors; Dietary Supplements; Female; Humans; Hyperandrogenism; Immunoassay; Kidney Failure, Chronic; Predictive Value of Tests; Testosterone
PubMed: 32840097
DOI: 10.4274/jcrpe.galenos.2020.2020.0064 -
Diagnostic Pathology Jul 2020Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However,... (Review)
Review
BACKGROUND
Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However, to the best of our knowledge, there are no publications in the existing literature that refer to the coexistence of 46, XY DSD and serous tumors in the ovary.
CASE PRESENTATION
Here, we report the case of a 23-year-old female (social gender) patient with 46, XY DSD presenting with primary amenorrhea. Imageology revealed a huge mass in the left adnexa. Subsequent pathological analysis revealed a serous borderline tumor of the ovary.
CONCLUSION
Gonadal tumors of patients with 46, XY DSD are not necessarily malignant tumors and can coexist with borderline tumors with primitive corded gonads. The coexistence of DSD and serous borderline tumors is rare. Clearly, an early and accurate diagnosis plays an important role in the treatment of these patients. Although there may not be a clear correlation between the two lesions, it is vital that we specifically analyze the mechanisms involved so that we can determine whether patients with DSD are associated with an increase of developing serous borderline tumors of the gonad.
Topics: Cystadenoma, Serous; Female; Gonadoblastoma; Humans; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovary; Sex Chromosome Aberrations; Sexual Development; Young Adult
PubMed: 32703224
DOI: 10.1186/s13000-020-01010-1 -
International Journal of Clinical and... 2014Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant... (Review)
Review
Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant germ cell components. We report the case of a 28 year-old female with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components. The germ cell portion contained multiple growth patterns with a malignant appearance, while the sex cord element consisted mainly of annular tubules. Within the malignant germ cell elements was a dysgerminoma that accounted for approximately 75% of the tumor volume. Other malignant germ cell elements included yolk sac tumor, embryonal carcinoma, and choriocarcinoma, which comprised about 15% of the tumor volume. The annular tubule structures comprised about 10% of the total tumor volume. To our knowledge, this is the first case reported in the literature of an unclassified mixed germ cell-sex cord-stromal tumor associated with embryonal carcinoma components. The patient had a 46XX karyotype, regular menstrual periods, and no evidence of gross abnormalities in the contralateral ovary. The patient remained clinically well and disease-free 2 years after surgery. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed.
Topics: Adult; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors
PubMed: 25197407
DOI: No ID Found -
The Turkish Journal of Pediatrics 201646, XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of 46, XY sexual development disorder. The patient presented to our clinic with absence of breast...
46, XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of 46, XY sexual development disorder. The patient presented to our clinic with absence of breast development and lack of periods at the age of 17 years. Her history and familial history involved no relevant conditions. She had Tanner stage 1 thelarche, and Tanner stage 2 pubic hair development with no axillary hair development. External genital structure appearance was consistent with female phenotype and the patient had no palpable gonad. The patient diagnosed as 46, XY complete gonadal dysgenesis after evaluation of laboratory analyses, radiological methods and karyotype. The Sexual Orientation and Gender Identity Committee concluded that gonadectomy should be performed. Histopathologic analysis demonstrated gonadoblastoma. Gonad structures should be sought laparoscopically and once diagnosed, streak gonads should be removed prophylactically in patients with 46, XY complete gonadal dysgenesis.
Topics: Adolescent; Female; Gonadal Dysgenesis; Gonadal Dysgenesis, 46,XY; Gonadoblastoma; Humans; Karyotype; Laparoscopy; Magnetic Resonance Imaging; Ovarian Neoplasms
PubMed: 28621097
DOI: 10.24953/turkjped.2016.05.013 -
Journal of the Endocrine Society May 2018Patients with Turner syndrome (TS) are known to be at risk for excess androgen production and virilization associated with gonadoblastoma and Y chromosome mosaicism, and...
Patients with Turner syndrome (TS) are known to be at risk for excess androgen production and virilization associated with gonadoblastoma and Y chromosome mosaicism, and excess androgens are a risk factor for the development of hepatocellular carcinoma. However, virilization and hepatocellular carcinoma have not been described in a patient with TS. A 10-year-old with nonmosaic 45,X TS presented with clitoromegaly, accelerated linear growth velocity, advanced bone age, and elevated testosterone levels as well as a second occurrence of hepatocellular carcinoma. Gonadectomy was performed, and pathology revealed hilus cell hyperplasia. Immunohistochemical staining of both the original and recurrent hepatocellular carcinoma tissues was diffusely positive for androgen receptors. After gonadectomy, testosterone levels were measurable but normal, with no further virilization; however, the liver mass continued to grow. Ovarian hilus cell hyperplasia should be considered a potential etiology for virilization in the TS population. Excess endogenous testosterone exposure in girls and women with TS may be associated with hepatocellular carcinoma expressing the androgen receptor, though normalizing testosterone levels may not lead to tumor regression in these cases.
PubMed: 29732458
DOI: 10.1210/js.2018-00017 -
American Journal of Human Genetics Dec 1995Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene...
Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was sublocalized to a small region near the centromere of the Y chromosome. We estimate the size of the GBY critical region to be approximately 1-2 Mb. Our analysis also indicates that copies of two dispersed Y-linked gene families, TSPY (testis-specific protein, Y-encoded) and YRRM (Y-chromosome RNA recognition motif) are present in all patients and that copies of TSPY but not YRRM fall within the GBY critical region as formally defined by deletion mapping. Two tumor samples showed expression of both genes and in one patient this expression was limited to a unilateral gonadoblastoma but absent in the contralateral streak gonad. Although our results do not directly implicate TSPY or YRRM in the etiology of the tumor, they raise the issue of whether there is one GBY gene in the critical region or possibly multiple GBY loci dispersed on the Y chromosome.
Topics: Adolescent; Base Sequence; Chromosome Mapping; Female; Gene Deletion; Gonadoblastoma; Humans; Male; Molecular Sequence Data; Ovarian Neoplasms; Polymerase Chain Reaction; Turner Syndrome
PubMed: 8533770
DOI: No ID Found -
Systems Biology in Reproductive Medicine Aug 2022")," individuals with rearranged Y chromosome breaks in their 46,XY cells are reported with male and female gender phenotypes and differences in germ cell tumour (GCT)...
")," individuals with rearranged Y chromosome breaks in their 46,XY cells are reported with male and female gender phenotypes and differences in germ cell tumour (GCT) risk. This raised the question of whether male or female gender and GCT risk depends on the site of the break and/or rearrangement of the individual´s Y chromosome. In this paper, we report molecular mapping of the breakpoint on the aberrant Y chromosome of 22 individuals with a 45,X/46,XY karyotype reared with a different gender. Their Y chromosome breaks are found at different sites on the long and short Y arms. Our data indicate that gender rearing is, neither dependent on the site of Y breakage, nor on the amount of 45,X0 cells in the individuals' leukocytes. Most prominent are secondary rearrangements of the Y chromosome breaks forming di-centric Y-structures ("dic-Y"). Duplications of the short Y arm and the proximal part of the long Y arm are the results. A putative GCT risk has been analysed with immunohistochemical experiments on some dysgenetic gonadal tissue sections. With specific antibodies for OCT3/4 expression, we marked the pluripotent germ cell fraction being potential tumour precursor cells. With specific antibodies for DDX3Y, TSPY, and UTY we analyzed their putative Gonadoblastoma Y (GBY) tumour susceptibility function in the same specimen. We conclude GBY expression is only diagnostic for GCT development in the aberrant germ cells of these individuals when strong OCT3/4 expression has marked their pluripotency.
Topics: Chromosome Breakage; Chromosomes, Human, Y; DEAD-box RNA Helicases; Female; Gonadoblastoma; Humans; Male; Minor Histocompatibility Antigens; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Phenotype; Sex Chromosome Disorders of Sex Development
PubMed: 35481403
DOI: 10.1080/19396368.2022.2057258 -
Molecular Cytogenetics 2015Females with Xp;Yq translocations manifest short stature and normal fertility, but rarely have follow-up. The study purpose was to define the phenotype of a family with...
BACKGROUND
Females with Xp;Yq translocations manifest short stature and normal fertility, but rarely have follow-up. The study purpose was to define the phenotype of a family with t(X;Y)(p22.3;q11.2), determine long-term reproductive function, and compare to all reported female cases.
METHODS
Comprehensive clinical and molecular analyses were performed on the female proband, who had regular menses, normal endocrine function, and three pregnancies spanning seven years--a normal liveborn male and two with unbalanced translocations (liveborn female and stillborn male).
RESULTS
The translocation truncated KAL1 and deleted 44 genes on der(X). Our report constitutes the longest follow-up of an X;Y translocation female. She had no evidence of Kallmann syndrome, gonadoblastoma, or cardiovascular disease. Detailed analysis of 50 published female cases indicated a uniform lack of follow-up and significant morbidity-intellectual disability (10%), facial dysmorphism (28%), eye abnormalities (14%), and skeletal defects (28%).
CONCLUSIONS
Our findings indicate normal ovarian function to date in a woman with an t(X;Y)(p22.3;q11.2). However, additional published studies in the literature suggest careful follow-up is necessary and contradict the generalization that females with Xp;Yq translocations are usually normal except for short stature.
PubMed: 25737742
DOI: 10.1186/s13039-015-0112-0