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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 -
Frontiers of Hormone Research 2019About 1% of ovarian tumors that comprise testicular cell types can cause hyperandrogenism followed by characteristic virilization. Androgenic group of tumors originated... (Review)
Review
About 1% of ovarian tumors that comprise testicular cell types can cause hyperandrogenism followed by characteristic virilization. Androgenic group of tumors originated mainly from sex-cord stromal ovarian tumors are including steroid cell tumors, Leydig tumors, granulosa cell tumors, Sertoli cell tumors, Sertoli-Leydig cell tumors, gonadoblastomas, and some other rare forms as ovarian metastases from neuroendocrine tumors. Germline or somatic mutations in some genes like DICER1, STK11, and FOXL2 are associated with the development of some sex cord-stromal ovarian tumors. Basal serum testosterone concentrations above 7 nmol/L could indicate an androgen-secreting tumor. Other ovarian and adrenal androgens should be determined and functional endocrine testing including low-dose dexamethasone suppression test, gonadotrophin-releasing hormone (GnRH) agonist test, imaging methods, and selective venous sampling should be performed. Surgery is the first-line treatment for most of the tumors. Women who are not good surgical candidates could benefit from use of GnRH agonist to control hyperandrogenism. In some cases, chemotherapy and/or radiation therapy is required while some tumors respond on antiangiogenic agents used alone or in combination with chemotherapy. Metabolic implications and long-term outcomes of ovarian androgen-secreting tumors are unknown and require more detailed follow-up in multicentric and longitudinal clinical studies.
Topics: Androgens; Female; Humans; Hyperandrogenism; Ovarian Neoplasms
PubMed: 31499493
DOI: 10.1159/000494906 -
Pathology, Research and Practice Nov 2020Gonadoblastoma occurring in a normal girl or woman has been confused with ovarian mixed germ cell-sex cord stromal tumor (MGC-SCST) due to a lack of knowledge that the...
Gonadoblastoma versus ovarian mixed germ cell-sex cord stromal tumor in women or girls with no evidence of a disorder of sex development: A problem in differential diagnosis.
Gonadoblastoma occurring in a normal girl or woman has been confused with ovarian mixed germ cell-sex cord stromal tumor (MGC-SCST) due to a lack of knowledge that the former occurs occasionally in a normal woman or girl. In this article, we develop histological criteria that facilitate the distinction of gonadoblastoma in an individual with a normal karyotype and no evidence of a disorder of sex development from ovarian MGC-SCST. We reviewed the histological findings of gonadoblastoma occurring in normal individuals and compared them to cases of ovarian MGC-SCST in our files. The histological findings of gonadoblastoma differ substantially from those of ovarian MGC-SCST. Importantly, gonadoblastoma contains two types of transformed germ cells, some histologically benign and others premalignant, whereas MGC-SCST contains only a single type, typically premalignant in the ovary and benign in the testis. Furthermore, degenerative changes of hyalinization and calcification are common in gonadoblastoma, whereas they are extremely rare in MGC-SCST. Although the great majority of cases of gonadoblastoma occur in an individual with a disorder of sex development and an abnormal karyotype, a substantial number arise in a normal woman or girl with no evidence of a disorder of sex development. In the latter circumstance, it is important to distinguish gonadoblastoma from ovarian MGC-SCST. It is very likely that those gonadoblastomas arising in a normal individual develop through a different molecular pathway than the ones that occur in the dysgenetic gonads of an individual with a disorder of sex development.
Topics: Adult; Child; Diagnosis, Differential; Female; Gonadoblastoma; Humans; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovary; Retrospective Studies; Sex Cord-Gonadal Stromal Tumors
PubMed: 33002849
DOI: 10.1016/j.prp.2020.153198 -
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 -
Archives of Gynecology and Obstetrics Feb 2012To present a challenging case of hCG positivity in a young patient and to review similar cases reported in the literature. (Review)
Review
OBJECTIVE
To present a challenging case of hCG positivity in a young patient and to review similar cases reported in the literature.
METHODS
Literature search of gonadoblastoma cases with pure 46, XX karyotype using PubMed database.
RESULTS
A 15-year-old girl with hCG positivity was investigated for the source and the initial diagnosis was an ectopic pregnancy. An ovarian tumor was identified after failed methotrexate therapy and the pathological diagnosis was gonadoblastoma with dysgerminoma. To the best of our knowledge, the case was unique in the literature for having the smallest diameter of a gonadoblastoma tumor with 46, XX karyotype.
CONCLUSION
Differential diagnosis of perimenarcheal vaginal bleeding may be challenging for the clinician. Rare causes such as pregnancy both intrauterine and extrauterine and hormone producing tumors should be kept in mind.
Topics: Adolescent; Chorionic Gonadotropin; Diagnosis, Differential; Dysgerminoma; Female; Gonadoblastoma; Humans; Karyotype; Ovarian Neoplasms; Pregnancy; Pregnancy, Ectopic; Uterine Hemorrhage
PubMed: 21879333
DOI: 10.1007/s00404-011-2073-9 -
Human Pathology Jun 2020Classical gonadoblastoma occurs almost entirely in the dysgenetic gonads of an individual who has a disorder of sex development; however, a small number of cases arise...
Classical gonadoblastoma occurs almost entirely in the dysgenetic gonads of an individual who has a disorder of sex development; however, a small number of cases arise in individuals with a normal peripheral karyotype and no evidence of a disorder of sex development. Those gonadoblastomas that occur in an individual who has a Y chromosome or part thereof express testis specific protein Y-encoded 1 (TSPY1). If a gonad in those individuals contains germ cells with delayed maturation and also harbors the TSPY1 gene, the cells can undergo transformation to classical gonadoblastoma. The latter consists of rounded islands composed of germ cells, sex cord elements, and hyaline basement membrane material surrounded by a variably cellular stroma that sometimes contains steroid cells. Classical gonadoblastoma can be interpreted as a noninvasive or an in situ neoplasm that is the precursor of germinoma in some individuals and, indirectly, of other more aggressive germ cell neoplasms. The "dissecting" variant is derived from classical gonadoblastoma and is characterized by unusual growth patterns. Undifferentiated gonadal tissue is the precursor of gonadoblastoma; however, if all germ cells in an individual with undifferentiated gonadal tissue involute, the result is a secondary streak gonad. Undifferentiated gonadal tissue is a non-neoplastic condition resembling a streak gonad but additionally contains germ cells with delayed maturation that express octamer-binding transcription factor 4; however, other germ cells, show normal maturation and express TSPY1.
Topics: Cell Cycle Proteins; Cell Differentiation; Cell Lineage; Chromosomes, Human, X; Chromosomes, Human, Y; Disorders of Sex Development; Female; Germ Cells; Gonadoblastoma; Humans; Male; Ovarian Neoplasms; Risk Factors; Testicular Neoplasms
PubMed: 31805291
DOI: 10.1016/j.humpath.2019.11.005 -
International Cancer Conference Journal Apr 2022Gonadoblastoma is an extremely rare neoplasm of the ovary showing admixture of germ cells and sex cord cells. It may be associated with gonadal dysgenesis....
Gonadoblastoma is an extremely rare neoplasm of the ovary showing admixture of germ cells and sex cord cells. It may be associated with gonadal dysgenesis. Gonadoblastoma cells may give rise to individual germ cell tumours or mixed germ cell tumours with variable tumour components. Very few cases of ovarian gonadoblastoma admixed with malignant germ cell tumours have been recorded worldwide. Because of the rareness of the tumour, a component of gonadoblastoma might be overlooked on microscopic examination. Here we report a rare case of ovarian gonadoblastoma giving rise to an admixture of immature teratoma and dysgerminoma. We discuss microscopic features, immunohistochemistry findings and review of literature.
PubMed: 35402135
DOI: 10.1007/s13691-021-00531-w -
Histopathology Mar 2018Classical gonadoblastoma occurs almost entirely in the dysgenetic gonads of an individual who has a disorder of sex development. Approximately 40% of such neoplasms are... (Review)
Review
Classical gonadoblastoma occurs almost entirely in the dysgenetic gonads of an individual who has a disorder of sex development. Approximately 40% of such neoplasms are bilateral. Almost all gonadoblastomas occur in patients who have a Y chromosome or part thereof; testis-specific protein Y-encoded 1 (TSPY1) is the putative gene. If a gonad in a patient who has a disorder of sex development contains germ cells with delayed maturation, and also harbours the TSPY1 gene, the cells can undergo transformation to classical gonadoblastoma. The latter consists of rounded islands composed of germ cells, sex cord elements and hyaline basement membrane material surrounded by a variably cellular gonadal stroma that sometimes contains steroid cells. Classical gonadoblastoma can be interpreted as a non-invasive neoplasm that is the precursor of germinoma and, indirectly, other more aggressive germ cell neoplasms. Undifferentiated gonadal tissue is the precursor of classical gonadoblastoma and contains germ cells with delayed maturation that express octamer-binding transcription factor 4 (OCT4); however, other germ cells show normal maturation and express TSPY1. If all germ cells in a patient with undifferentiated gonadal tissue involute, the result is a secondary streak. Undifferentiated gonadal tissue is a non-neoplastic condition that should be distinguished clearly from 'dissecting gonadoblastoma', a neoplasm derived from classical gonadoblastoma that is the precursor of some germinomas. 'Dissecting gonadoblastoma' is a variant of classical gonadoblastoma that has unusual growth patterns and contains both sex cord and germ cell elements. Clonal expansion of germ cells is a characteristic of the late stage of 'dissecting gonadoblastoma'.
Topics: Female; Gonadal Dysgenesis; Gonadoblastoma; Humans; Male; Ovarian Neoplasms; Testicular Neoplasms
PubMed: 28881049
DOI: 10.1111/his.13387 -
Annals of Diagnostic Pathology Aug 2010Gonadoblastomas are unusual benign neoplasias that frequently appear in the dysgenetic gonads of women with chromosome Y anomaly. In this study, we reviewed 3...
Gonadoblastomas are unusual benign neoplasias that frequently appear in the dysgenetic gonads of women with chromosome Y anomaly. In this study, we reviewed 3 gonadoblastoma cases, 2 of which were bilateral, in patients 21, 17, and 18 years of age. Two of them presented 46 XY karyotype and gonadal dysgenesis, whereas the third presented 46 XX karyotype. Besides, 2 of the cases were associated to dysgerminomas. In all the cases, the histologic examination showed germ cell proliferation and sex cords derivatives frequently surrounding small round deposits containing amorphous hyaline material resembling Call-Exner bodies. One of the patients died at 8 years from diagnosis because of dysgerminoma multiple metastases, one is alive with no evidence of disease at the second year of follow-up, and the evolution of the third patient remains unknown.
Topics: Adolescent; Female; Gonadal Dysgenesis; Gonadoblastoma; Humans; Male; Ovarian Neoplasms; Young Adult
PubMed: 20637428
DOI: 10.1016/j.anndiagpath.2010.03.006 -
Journal of Clinical and Diagnostic... Sep 2013Gonadoblastoma is a rare gonadal tumour consisting of a mixture of germ cells and sex cord stromal derivatives resembling immature granulosa and Sertoli cells. It...
Gonadoblastoma is a rare gonadal tumour consisting of a mixture of germ cells and sex cord stromal derivatives resembling immature granulosa and Sertoli cells. It usually arises in various types of gonadal dysgenesis containing Y chromosome like pure or mixed gonadal dysgenesis. Occurrence in phenotypically and chromosomally normal women is very rare. We report here a case of gonadoblastoma with dysgerminoma in a 14-years-old girl who presented with a huge tumour, virilisation and normal 46XX karyotype. Association of dysgerminoma is seen in 50% cases of gonadoblastomas. Elevated tumour markers like hCG and alpha Fetoprotein may make the diagnosis challenging.
PubMed: 24179931
DOI: 10.7860/JCDR/2013/6412.3393