Association of microscopic gonadoblastoma and contralateral ovarian fibroadenoma in patients with gonadal dysgenesis and Turner phenotype

A rare case of microscopic gonadoblastoma associated with gonadal fibroadenoma in a patient with gonadal dysgenesis and Turner phenotype is reported. The higher incidence of tumor pathologies in patients with gonadal dysgenesis presenting a Y chromosome in their karyotype is discussed, and the need for judicious microscopic analysis of the gonadal streaks of these patients for the detection of possible incipient tumors is emphasized.     

Bilateral ovariectomy in gonadal dysgenesis with a Y chromosome]

The Authors report 4 cases of gonadal dysgenesis with a Y chromosome. Every patient underwent bilateral oophorectomy. Two cases of streak gonads, 1 case of streak gonad and gonadoblastoma and 1 case of non metastasizing bilateral gonadoblastoma with foci of dysgerminoma have been found. The Authors emphasize the importance of early bilateral gonadectomy in all cases of gonadal dysgenesis with a Y chromosome.     

79例XY性腺发育异常患者性腺肿瘤发生情况分析

目的 探讨表型为女性、染色体含有Y或Y成分的性腺发育异常患者的性腺肿瘤发生情况.方法 1989年10月至2005年12月间于北京协和医院妇产科因性腺发育异常手术切除双侧性腺的患者共79例,所有患者均取外周血进行淋巴细胞染色体核型分析、Y基因性决定区检测以及相关激素和酶检测,影像学检查了解性腺位置.行经腹或腹腔镜下性腺切除术,所有手术标本均行病理检查.结果 79例患者中,雄激素不敏感综合征患者41例,其中发生精原细胞瘤1例、支持细胞腺瘤2例,占7%;170r羟化酶缺乏症患者14例,其中发生支持细胞腺瘤1例,占7%;XY单纯性腺发育不全患者4例,其中发生性腺母细胞瘤及无性细胞瘤1例,占1/4;XO/XY性腺发育不全患者16例,其中发生精原细胞瘤及性腺母细胞瘤1例,占6%;睾丸退化患者4例中无肿瘤发生.发生肿瘤的性腺多位于盆腔内,发生肿瘤的年龄集中于15～23岁.结论 表型为女性、染色体含有Y或Y成分的性腺发育异常患者易发生性腺母细胞瘤和生殖细胞肿瘤,一旦确诊宜及早切除双侧性腺.     

Familial 46,XY pure gonadal dysgenesis and gonadoblastoma/dysgerminoma: case report

The case reports of two sisters admitted for evaluation of primary amenorrhea are presented. Gynecological and endocrinological investigations and chromosomal analysis led to the diagnosis of familial 46,XY gonadal dysgenesis. Both sisters underwent bilateral salpingo-oophorectomy and hysterectomy. Histological examination revealed dysgenetic gonads with gonadoblastoma and dysgerminoma. Five years after treatment by surgery and irradiation the patients are well and free of recurrence. These cases again confirm the risk of malignancy and the necessity of prophylactic gonadectomy in all patients with gonadal dysgenesis and Y chromosomal material.     

Adnexal Torsion Due to Borderline Mucinous Tumor of the Gonad in a Prepubertal Girl with Mixed Gonadal Dysgenesis (45,X/46,XY) and a Turner Phenotype

BackgroundTurner 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.CaseWe 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 ConclusionGonadectomy 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.     

Gene-based screening for Y chromosome deletions in Taiwanese men presenting with spermatogenic failure

OBJECTIVE: To develop a simple and rapid protocol for detecting deletions of the Y chromosome and to evaluate the feasibility of gene-based screening in men with spermatogenic failure. DESIGN: Prospective case study. SETTING: University-based reproductive clinics and genetics laboratory. PATIENT(S): Two hundred two infertile men presenting with severe oligozoospermia and nonobstructive azoospermia. INTERVENTION(S): Fifteen gene-specific primers were used to detect deletions of Y chromosome genes in men with spermatogenic failure. A multiplex polymerase chain reaction amplification system was developed to facilitate rapid screening. Another 24 markers for sequence-tagged sites (STS) were used to ensure the adequacy of gene-based screening. MAIN OUTCOME MEASURE(S): Detection of deletions of Y chromosome genes. RESULT(S): Of 180 patients evaluated, 19 (10.6%) had deletions of one or more genes, including DFFRY, DBY, RBM1, DAZ, CDY1, and BPY2. A second round of STS-based screenings did not show an increase in the deletion rate but more clearly defined the extent of deletion in 14 of the 19 patients. In most patients, deletions detected by gene-based screening were similar to those detected by STS markers. CONCLUSION(S): Gene-based screening with multiplex polymerase chain reaction is a rational alternative for detecting deletions of Y chromosome genes in infertile men.     

Clinical,pathologic, and genetic findings in a case of 46, XY pure gonadal dysgenesis (Swyer's syndrome): I. Dysgerminoma and gonadoblastoma

Cytogenetic, pathologic, and clinical studies were conducted on a phenotypically female patient with primary amenorrhea and infertility. Analysis of blood cultures with routine and Giemsa-banded preparations indicated that the chromosomal complement of the patient was 46,XY. Buccal and peripheral blood smears prepared for fluorescent analyses confirmed the presence of a single F-body (Y chromosome). Pathologic examination of tissues removed at total hysterectomy and bilateral salpingo-oophorectomy revealed a gonadoblastoma of the right gonad, dysgerminoma of the left gonad, and an infantile hypoplastic uterus. The data were consistent with a diagnosis of 46,XY pure gonadal dysgenesis (Swyer's syndrome).     

Treatment of congenital anomalies in girls and women

The presence of a Y chromosome in patients with gonadal dysgenesis requires removal of the streak gonads for fear of tumor formation, the most likely one a gonadoblastoma. When estrogen-progestin replacement is given to patients with gonadal dysgenesis, sampling of the endometrium at regular intervals should be done in order to screen for endometrial hyperplasia. Obstructive lesions of the müllerian ducts should be diagnosed promptly to allow egress of the menstrual flow and preserve reproductive function. It is advisable to delay construction of an artificial vagina for patients with congenital absence of the vagina until such time as the patient is interested in sexual activity and motivated sufficiently to use a vaginal form on a regular basis postoperatively. Genetic females with ambiguous external genitalia should be evaluated carefully to make sure that they do not have the salt-losing variety of the adrenogenital syndrome, which can be life threatening.     

Laparoscopic gonadectomy in a case of a dicentric fluorescent Y-chromosome mosaicism with Turner-like phenotype and virilized external genitalia

In few cases of Turner syndrome the karyotype reveals the presence of an additional Y-bearing cell line, which is referred to as a borderline case of mixed gonadal dysgenesis. We report a 20-year-old woman with primary amenorrhea, virilization and a few Turner stigmata, who revealed rare mosaicism of 45,X/46,X dic (Y; 5)(q12; q11), +5/46,X, der (Y), which was detected by conventional G-banding and multicolor spectral karyotyping. She underwent laparoscopic gonadectomy in which mixed gonadal dysgenesis was found and both gonads were removed. No evidence of gonadoblastoma was noted on the gonads. Virilization improved postoperatively. We recommend gonadectomy via laparoscope in women presenting with Turner-like phenotype, virilization and the presence of a Y chromosome. This report describes the role of cytogenetic and molecular genetic investigations in the definition of mosaicism in Turner syndrome.     

Gonadoblastoma-Associated Mixed Gonadal Germ Cell Tumor with Dysgerminoma and Hepatoid Yolk Sac Tumor Components in 46XY Gonadal Dysgenesis

BackgroundDisorders of sex development are congenital conditions with atypical chromosomal, gonadal, or anatomical sex development. Gonadal dysgenesis in patients containing a Y chromosome have a high risk of developing germ cell tumors with potential for malignant transformation.CaseWe present the case of a 17-year-old phenotypic female with primary amenorrhea and 46,XY complete gonadal dysgenesis. Pelvic ultrasound showed a solid cystic lesion in the right gonad. Pathology showed a gonadoblastoma-associated mixed gonadal germ cell tumor with dysgerminoma and hepatoid yolk sac tumor.Summary and ConclusionTo our knowledge, this mixed neoplasm association has not been previously reported and this case illustrates the challenges for the diagnosis of gonadal dysgenesis-associated tumors, emphasizing its recognition and prognostic implications.     

Gonadoblastoma and dysgerminoma associated with XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of Frasier syndrome

STUDY OBJECTIVES: To report a rare reason for primary amenorrhea, a Frasier syndrome, XY gonadal dysgenesis associated with renal failure with eventual development of gonadoblastoma. To study immunohistochemical analysis of gonadoblastoma and dysgerminoma. To analyze the possibility of androgen receptor mutation in this rare syndrome. METHODS: We report a case of a 16-yr-old female with this syndrome. She underwent a laparoscopic bilateral gonadectomy and salpingectomy. A histopathological examination revealed gonadoblastoma with focal malignant dysgerminoma in the left dysgenetic gonad and an immunohistochemical of these fairly rare, malignant tumors. An androgen receptor was coded. Analysis was done. RESULTS: Immunohistochemical analysis showed that inhibin was strongly positive in gonadoblastoma but negative in dysgerminoma. No mutations of the androgen receptor gene were found. CONCLUSIONS: Inhibin positivity in gonadal stroma and in gonadoblastoma may indicate hormonal activity causing advanced puberty in patients with XY gonadal dysgenesis.     

A case of XY pure gonadal dysgenesis with 46,XYp-/47,XXYp- karyotype whose gonadoblastoma was removed laparoscopically

A case of pure gonadal dysgenesis was investigated. The patient was an 18-year-old Japanese woman with a history of primary amenorrhea. She had poorly developed breasts, a hypoplastic uterus, a normal vagina and infantile genitalia. The patient's karyotype was 46,XYp-/ 47,XXYp-. Microsatellite analysis revealed that the X chromosomes of this patient originated from one of the two maternal X chromosomes. DNA analysis of the Y chromosome revealed that she had a deletion of SRY (the sex-determining region on the Y chromosome). She underwent laparoscopic gonadectomies with a final pathology consistent with gonadoblastoma. Laparoscopic surgery is recommended as it is much less invasive and associated with rapid postoperative recovery.     

Hormonal and cytogenetic studies in phenotypically female patients with gonadal dysgenesis

In 4 cases of gonadal dysgenesis the clinical, hormonal, cytogenetic, and histological findings were correlated. There were 2 patients with 46,XY karyotype, one patient with 45,X Turner's syndrome and one patient with a 46,XX chromosome complement. All patients had streak gonads with ovarian stroma. In one phenotypically female 46,XY individual an involuted gonadoblastoma was found. Her testosterone was four-fold higher in gonadal vein blood compared to peripheral blood. Cytogenetic analysis of multiple tissues in both cases with the 46,XY karyotype greatly reduced the probability of mosaicism. In the patient with 45,X Turner's syndrome and in the one with 46,XX gonadal dysgenesis only peripheral blood cells were karyotyped and mosaicism was not further excluded by analysis of other tissues. The concentrations of steroid hormones in gonadal vein blood were low. The levels ranged as follows: estrone 41-98 pg/ml, estradiol 18-90 pg/ml, testosterone 37-294 ng/100 ml, dihydrotestosterone 13-22 ng/100 ml, and progesterone 0.3-1.5 ng/ml. It was concluded that gonadal streaks were similarly deficient in biosynthesis of steroid hormones despite different chromosomal complements.     

Y chromosome mosaicism and occurrence of gonadoblastoma in cases of Turner syndrome and amenorrhoea

In the present study, 73 cases with a clinical diagnosis of Turner syndrome, or with primary or secondary amenorrhoea without frank Turner phenotype, were evaluated for presence of low level Y chromosome mosaicism using molecular methods. Fluorescence in-situ hybridization for centromere and q arm of the Y chromosome and nested polymerase chain reaction for the sex determining region on Y (SRY) gene were performed in peripheral blood, buccal cells and gonadal biopsies. The overall frequency of Y chromosome mosaicism was found to be 18% (13/73 cases). Four cases (16%) of Turner syndrome had Y chromosome mosaicism, seven cases (28%) with primary amenorrhoea and two cases (9%) with secondary amenorrhoea had Y chromosome mosaicism. Histologically detectable gonadoblastoma was observed in one of seven cases (14%) that had Y chromosome mosaicism. This frequency is lower than that reported previously, underscoring the need for large prospective investigations to determine the frequency of Y chromosome mosaicism and occurrence of gonadoblastoma in cases of Turner syndrome and other forms of amenorrhoea.     

The pure gonadal dysgenesis syndrome.

Two cases of gonadal dysgenesis in phenotypic females associated with different chromosomal patterns are discussed. Both patients presented with primary amenorrhea and were characterized by tall stature and underdeveloped secondary sex characteristics and external and internal reproductive organs. The karyotype of the first patient was 46,XX with a satellite on chromosome 17. The second patient had a normal female chromosome composition (46,XX) with a past history of mumps. Laparoscopic bilateral gonadal biopsies in both patients revealed fibrous tissue without any primordial follicles. This report emphasizes the pathogenesis, clinical significance, diagnosis and management of gonadal dysgenesis.     

Malignant Stromal Tumour of the Ovary with Virilizing Effects in an XXX Female with Streak Ovaries

Summary: In gonadal dysgenesis, the presence of the Y sex chromosome appears to have a strong influence on the development of germ cell tumours. The risk of malignancy associated with other sex chromosomal abnormalities is much lower. In the present report, the clinical manifestations – including primary amenorrhoea, tall stature, infertility and poor development of the genitalia and breasts – associated with a predominantly 47, XXX karyotype are described. Malignant change of the streak ovary to an unusual gonadal stromal tumour with lipid-containing cells occurred at a late stage in her life, and this was associated with progressive virilization and production of androgenic and oestrogenic steroids. In view of the risk of malignancy as well as the abnormal endocrine effects, especially in the presence of a Y chromosome, there is a place for the prophylactic removal of these dysgenetic gonads.     

Turner综合征Y染色体物质嵌合分子遗传学研究

摘要：目的　分析Turner综合征（TS）患儿Y染色体物质及衍生物嵌合发生的情况，为TS患儿诊断后的监测提供科学建议，改善国内TS监测和保健管理的现状。方法　选取2006年2月至2007年8月在重庆医科大学附属儿童医院诊断为TS患儿30例，进行基因组DNA 的Y编码睾丸特异性蛋白基因（TSPY）、 Y染色体中心着丝粒DYZ3重复序列（DYZ3 ）和Y性别决定区域（SRY）3个Y染色体特异序列多聚酶链反应（PCR）检测，反应结果阳性的病例补充SRY探针原位荧光杂交（FISH）分析。结果　基因组DNA 的PCR结果显示，3例患儿的TSPY、 DYZ3扩增均为阳性（10.00%），其中只有1例 SRY 扩增阳性（3.33%）；3例Y染色体物质阳性病例进一步进行FISH研究，结果显示3例SRY杂交信号均为阳性。结论　运用3个Y染色体特异序列的分子遗传学研究，证实Y染色体物质嵌合在TS不少见，每一个TS患儿都应在诊断后进行Y染色体物质的分子遗传学监测。     

Management of phenotypic female patients with an XY karyotype

Nine phenotypic female patients with XY karyotype were evaluated through a clinical, cytogenetic, hormonal, endoscopic and histologic diagnostic protocol. Seven patients complained of primary amenorrhea and two patients of abnormal puberal development. The final diagnosis was XY gonadal dysgenesis (n = 5) and testicular feminization syndrome (n = 4). Two patients were less than 155 cm tall, and the remainder were over 155. Minor somatic anomalies were found in two patients with XY gonadal dysgenesis. Patient with testicular feminization syndrome had FSH and LH within the normal range, and patients with XY gonadal dysgenesis had elevated FSH and LH levels. Gonadoblastomas were found in two patients with XY gonadal dysgenesis (one patient with XO/XX/XY mosaicism). Laparoscopy and gonadal biopsy might be useful in some patients to avoid confusion between XY gonadal dysgenesis and testicular feminization syndrome. Early diagnosis of XY gonadal dysgenesis is always desirable, and bilateral gonadectomy is indicated as soon as the diagnosis is made in patients with a Y chromosome and elevated FSH levels. Surgical removal of the gonads from patients with testicular feminization should be delayed until the completion of puberty because of the low risk of malignancy.