RESUMO
BACKGROUND: Y chromosome material stands as an independent risk determinant for the onset of gonadoblastoma (GB) and subsequent gonadal germ cell tumours in individuals with Turner syndrome (TS). However, the delayed and underestimated identification of Y chromosome material through karyotyping within primary care settings exacerbates the intricacies of managing these patients over the long term. METHODS: We present a case involving TS accompanied by Y chromosome material, wherein puberty delay and GB were identified during prophylactic gonadectomy. Subsequently, we delve into the literature to explore the GB-related malignancy risk in TS patients with Y chromosome material, the incidence of Y chromosome presence in TS patients using methodologies beyond routine chromosomal testing, and the diagnosis and treatment of puberty delay in TS patients, all based on our case. RESULTS: A spectrum of more sensitive molecular techniques, including polymerase chain reaction (PCR) and fluorescence in situ hybridisation, effectively augments the detection of Y chromosome material alongside karyotyping. In addition to gonadectomy, the implementation of appropriate oestrogen therapy and a holistic, multidisciplinary approach to care can enhance the quality of life, while mitigating the long-term morbidity and mortality risks for TS patients harbouring Y chromosome material. CONCLUSIONS: Beyond gonadectomy, adopting a multifaceted approach the Y chromosome material detection, prompt initiation of puberty, tailored oestrogen therapy, and coordinated multidisciplinary management significantly contributes to the comprehensive health oversight of TS patients with Y chromosome material.
Assuntos
Gonadoblastoma , Neoplasias Ovarianas , Síndrome de Turner , Feminino , Humanos , Síndrome de Turner/complicações , Síndrome de Turner/genética , Gonadoblastoma/genética , Gonadoblastoma/complicações , Gonadoblastoma/diagnóstico , Qualidade de Vida , Puberdade , Neoplasias Ovarianas/genética , EstrogêniosRESUMO
Germ cell tumors (GCTs) are associated with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome usually presents with primary amenorrhea, streak ovaries, and mixed GCT. However, our patient presented with secondary amenorrhea, normal female external genitalia, and a mixed GCT. Constitutional karyotype was suggestive of 46,XY. Management comprised chemotherapy, followed by surgery. Histopathology was suggestive of dysgerminoma complicating a gonadoblastoma. The purpose of reporting this case is its rarity and the importance of diagnosing an XY karyotype, as the incidence of GCTs is higher in these patients.
Assuntos
Disgerminoma , Disgenesia Gonadal 46 XY , Gonadoblastoma , Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Amenorreia/complicações , Disgerminoma/diagnóstico , Disgerminoma/terapia , Disgerminoma/patologia , Gonadoblastoma/complicações , Gonadoblastoma/diagnóstico , Gonadoblastoma/patologia , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal 46 XY/complicações , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Embrionárias de Células Germinativas/complicaçõesRESUMO
Objective: To summarize the experience in diagnosis and treatment of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism and bilateral gonadoblastoma (Gb) secreting human chorionic gonadotrophin(HCG). Methods: A female patient aged 5 years and 3 months was admitted to the hospital with a complaint of "enlarged breasts for 27 months, and elevated blood ß-HCG for 8 months". The clinical data were summarized, and related literature up to March 2022 with the key words"Turner syndrome" "Gonadoblastoma" "Y chromosome" "human chorionic gonadotropin" "precocious" in PubMed, CNKI and Wanfang databases were reviewed. Results: The girl went to the local hospital for 2-month breast development at age of 3 years, and was found with a heart murmur diagnosed with "pulmonary venous malformation and atrial septal defect (secondary foramen type)". Surgical correction was performed. She experienced the progressive breast development, rapid linear growth and markedly advanced skeletal age, which cannot be explained by partial activation in the hypothalamic-pituitary-gonadal axis determined at the age of 3 years and 7 months in local hospital. Then whole-exome sequencing revealed chromosome number abnormality 45, X, which was confirmed by Karyotyping. At the age of 4 years and 6 months, serum ß-HCG was found to be elevated (24.9 U/L) with no lesion found at the local hospital. On physical examination, she was found with breast development, pubic hair development and clitoromegaly with elevated serum testosterone (1.96 µg/L) and ß-HCG (32.3 U/L). Sex determining region Y(SRY) gene was negative in peripheral blood sample. Thoracic and abdominal CT, head and pelvic magnetic resonance imaging were normal. Exploratory laparotomy confirmed the presence of a left adnexal tumor and a right fibrous streak gonad. During surgery, simultaneous samples of bilateral gonadal and peripheral venous blood were obtained and serum ß-HCG, estradiol and testosteron concentrations was higher to lower from left gonadal venous blood, right gonadal venous blood, to peripheral venous blood. Bilateral gonadectomy was performed. Histopathology revealed bilateral gonadoblastomas. SRY was positive in bilateral gonadal tissues. After surgery, serum E2, testerone and ß-HCG returned to normal. So far 4 cases of HCG-secreting gonadoblastoma had been reported worldwide. The phenotypes of the 4 cases were all female, with virilization or amenorrhea, and the preoperative peripheral blood ß-HCG concentrations were 74.4, 5.0, 40 456.0, and 42.4 U/L, respectively. Conclusions: There is a high risk of Gb in TS with Y chromosome components. Gb is infrequently presented with breast development, and Gb associated with HCG secretion is rare. Karyotyping should be performed in a phenotypic female with masculinization, and virilization in TS indicates the presence of Y chromosome material with concurrent androgen secreting tumors.
Assuntos
Gonadoblastoma , Neoplasias Ovarianas , Síndrome de Turner , Humanos , Feminino , Pré-Escolar , Gonadoblastoma/complicações , Gonadoblastoma/genética , Gonadoblastoma/cirurgia , Síndrome de Turner/complicações , Virilismo , Gonadotropina CoriônicaRESUMO
BACKGROUND: Turner syndrome (TS) is a sex chromosome condition characterized by complete or partial loss of the X chromosome. Patients with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype are predisposed to gonadoblastoma with malignant transformation. CASE: We present the case of a TS patient with 45,X/46,XY with 2 episodes of left adnexal torsion (AT). Biopsies during detorsion showed benign mucinous cystadenoma. Pathology following bilateral gonadectomy revealed a left gonad with mucinous borderline tumor and right gonad with gonadoblastoma, both of which have malignant potential. SUMMARY AND CONCLUSION: Gonadectomy is recommended in XY gonadal dysgenesis to decrease risk of malignant transformation from gonadoblastoma. Although rare in pediatric patients, ovarian malignancies have been identified among AT cases. To our knowledge, we present the first case of AT due to borderline ovarian mucinous tumor of the ovary and contralateral gonadoblastoma in a patient with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype.
Assuntos
Disgenesia Gonadal 46 XY , Disgenesia Gonadal Mista , Disgenesia Gonadal , Gonadoblastoma , Neoplasias Ovarianas , Síndrome de Turner , Feminino , Gonadoblastoma/complicações , Gonadoblastoma/genética , Gonadoblastoma/cirurgia , Gônadas/patologia , Humanos , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Torção Ovariana , Fenótipo , Síndrome de Turner/complicações , Síndrome de Turner/genéticaRESUMO
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 CYP17A1 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.
Assuntos
Disgerminoma , Gonadoblastoma , Liases , Neoplasias Ovarianas , Humanos , Feminino , Criança , Disgerminoma/complicações , Disgerminoma/diagnóstico , Disgerminoma/genética , Oxigenases de Função Mista , Gonadoblastoma/complicações , Gonadoblastoma/diagnóstico , Gonadoblastoma/genética , Hidrocortisona , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genética , CariótipoRESUMO
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the NBN gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Nibrin is also involved in gonadal development and its disfunction in females with NBS frequently results in a pure gonadal dysgenesis (PGD) causing hypergonadotropic hypogonadism. However, only a few ovarian tumors in NBS patients have been reported to date. We describe the first case of a girl with NBS with PGD, who developed metachronous bilateral ovarian germ cell tumors (dysgerminoma and gonadoblastoma). Pathogenesis of PGD, neoplastic transformation and therapeutic approach in females with NBS are discussed.
Assuntos
Disgenesia Gonadal , Gonadoblastoma , Hipogonadismo , Síndrome de Quebra de Nijmegen , Neoplasias Ovarianas , Feminino , Disgenesia Gonadal/complicações , Disgenesia Gonadal/genética , Gonadoblastoma/complicações , Gonadoblastoma/genética , Humanos , Hipogonadismo/genética , Síndrome de Quebra de Nijmegen/complicações , Síndrome de Quebra de Nijmegen/diagnóstico , Síndrome de Quebra de Nijmegen/genética , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genéticaRESUMO
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.
Assuntos
Cistadenoma Seroso/patologia , Gonadoblastoma/patologia , Neoplasias Ovarianas/patologia , Aberrações dos Cromossomos Sexuais , Desenvolvimento Sexual/fisiologia , Cistadenoma Seroso/diagnóstico , Feminino , Gonadoblastoma/complicações , Gonadoblastoma/diagnóstico , Humanos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/diagnóstico , Ovário/patologia , Adulto JovemRESUMO
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.
Assuntos
Disgerminoma/diagnóstico , Gonadoblastoma/diagnóstico , Neoplasias Ovarianas/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Adulto , Animais , Proliferação de Células/genética , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Disgerminoma/complicações , Disgerminoma/patologia , Disgerminoma/veterinária , Feminino , Gonadoblastoma/complicações , Gonadoblastoma/patologia , Gonadoblastoma/veterinária , Humanos , Cariótipo , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/veterinária , Ovário/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-kit/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/complicações , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/veterinária , Células Estromais/patologia , Cromossomo Y/genéticaAssuntos
Disgerminoma/diagnóstico , Disgenesia Gonadal 46 XY/patologia , Gonadoblastoma/diagnóstico , Linfonodos/patologia , Metástase Linfática/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adolescente , Disgerminoma/complicações , Disgerminoma/cirurgia , Feminino , Disgenesia Gonadal 46 XY/cirurgia , Gonadoblastoma/complicações , Gonadoblastoma/cirurgia , Humanos , Histeroscopia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgiaRESUMO
Gonadoblastomas (GBYs) are rare gonadal tumors almost always arising from a dysgenetic gonad with a Y chromosome. Very rarely, GBYs appear in otherwise normal women with a history of pregnancy. The typical histological appearance of GBY can be altered by extensive deposition of basement membrane material, calcification, or overgrowth by a malignant tumor. Less than 10 cases have been reported with normal 46XX karyotype. Only six cases of GBY have been described in pregnant women. We present a unique case of GBY with dysgerminoma in a genotypically and phenotypically normal woman with a history of normal pregnancy, absence of virilization, and characteristic immunohistomorphological features.
Assuntos
Disgerminoma/diagnóstico , Disgerminoma/etiologia , Gonadoblastoma/complicações , Gonadoblastoma/diagnóstico , Fosfatase Alcalina/análise , Biomarcadores Tumorais/análise , Disgerminoma/patologia , Feminino , Proteínas Ligadas por GPI/análise , Gonadoblastoma/patologia , Histocitoquímica , Humanos , Imuno-Histoquímica , Inibinas/análise , Isoenzimas/análise , Microscopia , Gravidez , Vimentina/análise , Adulto JovemRESUMO
BACKGROUND: It is recognised that individuals with a 45,X/46,XY karyotype, known as Turner mosaic syndrome with Y chromosome material (TMSY), have an increased risk of developing gonadoblastoma (GB), which may then devolve into one of a number of germ cell malignancies. Hence, children with TMSY are usually recommended to undergo prophylactic gonadectomy. OBJECTIVE: We designed this study to describe the phenotypic features of our series of children with TMSY who underwent prophylactic gonadectomy in order to evaluate the prevalence of GB and germ cell malignancies in their resected specimens. STUDY DESIGN: This is a retrospective case series wherein we comprehensively reviewed the clinical, histological, and cytogenetic features of all patients who underwent prophylactic gonadectomy at three tertiary paediatric referral centres over 16 years. Cases were identified from surgical logbooks and through the institutional histopathology database. Data were collected with particular reference to clinical phenotype, predominant karyotype cell line, operative management, anatomical findings and the presence of neoplastic changes. RESULTS: Fourteen children ranging in age at the time of surgery from 2 weeks to 17 years were included in the series. Eleven children were reared as females. The three children who were reared as males had severe penoscrotal hypospadias. The 46,XY cell line was the predominant cell line in seven (50%) cases in blood lymphocytes. The resected specimens from four patients (28.6%) contained GB, with three patients having bilateral GB. This sub-group of patients with GB were aged 5 months, 48 months, 71 months, and 13 years. GB arose in one patient with and three patients without genital virilisation. There was no focus of invasive germ cell tumour in any specimen. DISCUSSION: GB may be present in infants with TMSY as young as 5 months, even with low levels of Y chromosome material. The prevalence of GB in prophylactic gonadectomy specimens is similar to many previously reported series, although the absence of dysgerminoma in our series is reassuring. The exclusive presence of GB in intra-abdominal gonads is in keeping with the findings of several other series. CONCLUSION: Owing to the presence of gonadoblastoma in the gonads of children with TMSY as young as 5 months, we recommend that all patients with intra-abdominal gonads in the context of TMSY should duly undergo prophylactic gonadectomy, although the timing of such surgery can be discussed with parents during counselling regarding the risk of malignancy.
Assuntos
Gonadoblastoma/genética , Mosaicismo , Neoplasias Ovarianas/genética , Neoplasias Testiculares/genética , Síndrome de Turner/genética , Adolescente , Criança , Pré-Escolar , Feminino , Gonadoblastoma/complicações , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Ovarianas/complicações , Estudos Retrospectivos , Neoplasias Testiculares/complicações , Síndrome de Turner/complicaçõesRESUMO
Ovotesticular disorder of sexual development (DSD), formerly known as true hermaphroditism, is a rare form of DSD in which both testicular and ovarian tissues are present in the same individual either in a single gonad (ovotestis) or in opposite gonads with a testis and an ovary on each side. The diagnosis of ovotesticular DSD is based solely on the presence of ovarian and testicular tissue in the gonad and not on the characteristics of the internal and external genitalia, even if ambiguous. Herein, we report two patients with ovotesticular DSD-one presenting with ambiguous genitalia on the third day after birth and the other with short stature and primary amenorrhea in adolescence. Clinical and histopathological investigation revealed a sex-determining region on the Y chromosome (SRY)-positive 46,XX karyotype and bilateral ovotestes in case 1 and a 46,XY karyotype with hypergonadotropic hypogonadism and a streak gonad in one ovotestis with dysgerminoma, gonadoblastoma, and papillary tubal hyperplasia in the contralateral ovotestis in case 2. Laparoscopic examination and gonadal biopsy for histopathological diagnosis remain the cornerstones for a diagnosis of ovotesticular DSD. Moreover, SRY positivity in a 46,XX patient, a 46,XY karyotype, an intra-abdominal gonad, and the age of patient at the time of diagnosis are predictive risk factors for the development of gonadoblastoma and/or dysgerminoma in ovotesticular DSD.
Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , Tubas Uterinas/patologia , Gonadoblastoma/diagnóstico , Neoplasias Ovarianas/diagnóstico , Transtornos Ovotesticulares do Desenvolvimento Sexual/diagnóstico , Adolescente , Transtornos do Desenvolvimento Sexual/complicações , Transtornos do Desenvolvimento Sexual/genética , Feminino , Gonadoblastoma/complicações , Humanos , Hiperplasia , Recém-Nascido , Cariótipo , Masculino , Neoplasias Ovarianas/complicações , Transtornos Ovotesticulares do Desenvolvimento Sexual/complicações , Transtornos Ovotesticulares do Desenvolvimento Sexual/genéticaRESUMO
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.
Assuntos
Disgenesia Gonadal 46 XY/complicações , Disgenesia Gonadal/complicações , Gonadoblastoma/complicações , Adolescente , Feminino , Humanos , Cariótipo , Laparoscopia , Imageamento por Ressonância Magnética , Neoplasias Ovarianas/cirurgiaRESUMO
The presence of the Y chromosome in the karyotype of patients with disorders of sex differentiation is significantly associated with an increased risk to develop specific types of malignancies, predominantly type II germ cell tumors (GCTs). Gonadoblastoma in the gonads without an obvious testicular differentiation and intratubular germ cell neoplasia of unclassified type in testicular tissue are the precursor lesions of most GCTs. Gonadal dysgenesis, the characteristic feature of Ullrich-Turner syndrome (UTS), further contributes to increase this tumor risk. The reported incidence of Y chromosome material in UTS is 6 to 8% and in these cases an early gonadectomy is strongly recommended to prevent the risk of a malignancy. The aim of this work was to retrospectively analyze the clinical outcome and the histopathological and cytogenetic findings of our UTS patients who underwent gonadectomy to establish strict selection criteria aimed at promoting an organ-sparing surgery.
Assuntos
Cromossomos Humanos Y/genética , Disgerminoma/patologia , Gonadoblastoma/patologia , Gônadas/cirurgia , Neoplasias Ovarianas/patologia , Síndrome de Turner/complicações , Síndrome de Turner/genética , Adolescente , Proteínas de Ciclo Celular/genética , Criança , Cromossomos Humanos Y/ultraestrutura , Disgerminoma/genética , Disgerminoma/cirurgia , Feminino , Predisposição Genética para Doença , Gonadoblastoma/complicações , Gonadoblastoma/genética , Gonadoblastoma/cirurgia , Gônadas/patologia , Humanos , Cariotipagem , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Procedimentos Cirúrgicos Profiláticos , Estudos Retrospectivos , Fatores de Risco , Fatores de Transcrição SOXB1/genética , Síndrome de Turner/patologiaRESUMO
Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases. A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of estradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty. Genetic studies revealed 46 XY karyotype with mutation c.89G> T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma.
Assuntos
Disgenesia Gonadal 46 XY/etiologia , Gonadoblastoma/complicações , Neoplasias Ovarianas/complicações , Puberdade Precoce/etiologia , Pré-Escolar , Feminino , Gonadoblastoma/diagnóstico , Humanos , Neoplasias Ovarianas/diagnósticoRESUMO
Gonadal dysgenesis (GD) is a rare congenital malformation that affects about one in 3,000 births. The authors present a case of a 17-year-old woman with primary amenorrhea and poor breast development. They conducted a laparoscopic surgery and bilaterally removed hypoplastic streak gonads. Histopathology of the ovaries revealed bilateral streak gonads with gonadoblastomas and a right-sided dysgerminoma.
Assuntos
Disgerminoma/complicações , Disgenesia Gonadal 46 XY/complicações , Neoplasias Ovarianas/complicações , Adolescente , Amenorreia/etiologia , Disgerminoma/patologia , Disgerminoma/cirurgia , Feminino , Gonadoblastoma/complicações , Gonadoblastoma/patologia , Gonadoblastoma/cirurgia , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgiaRESUMO
Activating c-KIT mutations (exons 11 and 17) are found in 10-40% of testicular seminomas, the majority being missense point mutations (codon 816). Malignant ovarian dysgerminomas represent ~3% of all ovarian cancers in Western countries, resembling testicular seminomas, regarding chromosomal aberrations and c-KIT mutations. DSD patients with specific Y-sequences have an increased risk for Type II Germ Cell Tumor/Cancer, with gonadoblastoma as precursor progressing to dysgerminoma. Here we present analysis of c-KIT exon 8, 9, 11, 13 and 17, and PDGFRA exon 12, 14 and 18 by conventional sequencing together with mutational analysis of c-KIT codon 816 by a sensitive and specific LightCycler melting curve analysis, confirmed by sequencing. The results are combined with data on TSPY and OCT3/4 expression in a series of 16 DSD patients presenting with gonadoblastoma and dysgerminoma and 15 patients presenting pure ovarian dysgerminomas without DSD. c-KIT codon 816 mutations were detected in five out of the total of 31 cases (all found in pure ovarian dysgerminomas). A synonymous SNP (rs 5578615) was detected in two patients, one DSD patient (with bilateral disease) and one patient with dysgerminoma. Next to these, three codon N822K mutations were detected in the group of 15 pure ovarian dysgerminomas. In total activating c-KIT mutations were found in 53% of ovarian dysgerminomas without DSD. In the group of 16 DSD cases a N505I and D820E mutation was found in a single tumor of a patient with gonadoblastoma and dysgerminoma. No PDGFRA mutations were found. Positive OCT3/4 staining was present in all gonadoblastomas and dysgerminomas investigated, TSPY expression was only seen in the gonadoblastoma/dysgerminoma lesions of the 16 DSD patients. This data supports the existence of two distinct but parallel pathways in the development of dysgerminoma, in which mutational status of c-KIT might parallel the presence of TSPY.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Disgerminoma/genética , Gonadoblastoma/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Testiculares/genética , Adolescente , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Criança , Pré-Escolar , Análise Mutacional de DNA , Transtornos do Desenvolvimento Sexual/complicações , Transtornos do Desenvolvimento Sexual/patologia , Disgerminoma/complicações , Disgerminoma/patologia , Feminino , Gonadoblastoma/complicações , Gonadoblastoma/patologia , Humanos , Lactente , Masculino , Mutação , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologiaRESUMO
Germ cell tumors are the most frequent ovarian neoplasms among girls and young women under the age of 25. Female patients with gonadal dysgenesis are at higher risk of germ cell tumors. Two cases of women with pure gonadal dysgenesis were described. A hormonally active tumor secreting estrogens, caused the development of sexual features and genital tract bleeding what imitated premature puberty. It needs to be emphasized that the presence of sexual features does not exclude dysgenesis - a pathology that is connected with an increased risk of gonadal tumors--and that the ultrasound evaluation, during which the presence of follicles in gonads is evaluated, is essential.