1/53. gonadoblastoma, mixed germ cell tumor, and Y chromosomal genotype: molecular analysis in four patients. This study reports on Y chromosomal genotypes of three patients with gonadoblastoma and one patient with gonadoblastoma and mixed germ cell tumor. Molecular analysis for 35 Y chromosomal loci was performed for dna samples taken from peripheral leukocytes and lymphoblastoid cell lines, showing that the four patients shared the region between DYS267 at interval 4A and DYF50S1 at interval 6D, with the exception of the region around DYS202 at interval 5K. In the patient with gonadoblastoma and mixed germ cell tumor, Y chromosomal material was preserved in the gonadoblastoma but was lost from the mixed germ cell tumor. The results, in conjunction with previous reports, suggest that GBY (gonadoblastoma locus on the y chromosome) may be located to a roughly 5-Mb pericentromeric region between DYS267 at interval 4A and DYS270 at interval 5A. The presence of Y chromosomal material in gonadoblastoma is consistent with GBY being involved in the development of gonadoblastoma, and the absence of Y chromosomal material in mixed germ cell tumor would be explained as a consequence of Y chromosomal loss from rapidly proliferating gonadal cancer cells. ( info) |
2/53. Case of gonadoblastoma in a 9-year-old boy without physical abnormalities. BACKGROUND: A 9-year-old boy was admitted to Jikei University Hospital complaining of gradual enlarging of the left scrotal contents. methods/RESULTS: physical examination was significant for bilateral descended testicles. No abnormalities were detected in the testicles or along the spermatic cords. Scrotal ultrasound showed that hyperechoic shadows were recognized in the central area of the left testicle. Subsequent testicular biopsy and histopathological examination showed intratubular malignant germ cells in the testicular tubules. One week later, left orchiectomy was performed. CONCLUSIONS: Histopathological evaluation revealed gonadoblastoma. gonadoblastoma, a rare gonadal neoplasm, is composed of germ cells and sex cord derivatives and usually occurs in phenotypically female patients with gonadal dysgenesis. To date, only three cases of gonadoblastoma have been reported in anatomically normal male patients with scrotal testicles. We report on a case of gonadoblastoma unaccompanied by a germ cell tumor in a physically normal male. ( info) |
| We report two female patients with gonadal dysgenesis and sex chromosome mosaicism involving the y chromosome. Conventional karyotyping was supplemented with fluorescent in situ hybridisation techniques in order to confirm the presence of Y chromosomes. One patient is a phenotypic female with karyotype 45,X/46,X,idic(Y)(q11.2). She underwent a laparoscopic gonadectomy at which streak ovaries without evidence of gonadoblastoma were removed. The second patient presented as a virilised female with karyotype 45,X/47,XYY. At laparoscopy, she was found to have mixed gonadal dysgenesis with a gonadoblastoma in situ. We recommend early gonadectomy in female children presenting with gonadal dysgenesis and the presence of a y chromosome although once the gonadoblastoma locus on y chromosome gene has been cloned it may be possible to identify those patients who have a low risk of developing gonadoblastoma. ( info) |
| We report three patients with XY pure gonadal dysgenesis. Two of these patients developed gonadoblastoma and associated dysgerminoma. Molecular analyses were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations. Deletion analyses were performed by polymerase chain reaction (PCR) amplification of y chromosome-specific dna sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the y chromosome that included the PABY, SRY, DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an associated tumor. In the other two patients who did not demonstrate such a deletion, the sequence of the SRY open reading frame was determined by the dideoxynucleotide method. Two nucleotide substitutions followed by a seven nucleotide deletion were observed in the 3' end of HMG (high mobility group)-box in the other patient (15-years-old) with an associated tumor. The patient (22-years-old) without an associated tumor did not have the cryptic deletion or mutation of SRY. A y chromosome specific sequence (DYZ1) was demonstrated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation of gonadal tumors, especially dysgerminoma. ( info) |
5/53. Detection of TSPY protein in a unilateral microscopic gonadoblastoma of a Turner mosaic patient with a Y-derived marker chromosome. Gonadoblastomas are seen almost exclusively in dysgenetic gonads of patients with a chromosomal mosaicism of 45,X and an additional Y-bearing cell line. This paper presents a case of a Turner mosaic patient with 45,X/46,X, mar karyotype, who developed a unilateral microscopic gonadoblastoma. Cytogenetic and molecular analysis confirmed a Y-chromosomal origin of the marker chromosome, with a deletion of the distal Yq arm and the proposed region of a so far undefined gonadoblastoma locus (GBY) present. One of the candidate genes within the postulated GBY region is TSPY (testis-specific protein Y-encoded). To study the TSPY protein expression, an anti-fusion protein antibody was used for immunohistochemistry of the patient's gonads. In contrast to the dysgenetic gonad, an intense immunoreaction was found in gonadoblastoma tumour cells of the other gonad. These results confirm the high level of TSPY protein expression by these cells and demonstrate the value of this antibody as an additional marker to confirm the diagnosis of gonadoblastoma. ( info) |
6/53. A novel missense mutation in the HMG box region of the SRY gene in a Japanese patient with an XY sex reversal. The sex-determining region of the y chromosome, the SRY gene, located on the short arm of the y chromosome, is appreciated as one of the genes that is responsible for directing the process of sex differentiation. To date, 34 different mutations, including 29 missense and nonsense mutations in the SRY gene, have been described in XY female patients. We investigated the molecular basis of the sex reversal in one Japanese XY female patient by determining the nucleotide sequence of the SRY gene, using polymerase chain reaction and direct sequencing. We identified a novel mutation, of the substitution of Tyr for Asn at nucleotide position 87 (N87Y). This Asn residue is located within the dna-binding high-mobility-group (HMG) motif, which is considered to be the main functional domain of the SRY protein. Further, this amino acid, Asn, is a conserved residue among mammalian SRY genes. These findings indicate that this amino acid substitution may be responsible for the sex reversal in this patient. ( info) |
| Gonadoblastomas are known to be hormonally active tumors that occur in streak or dysgenetic gonads of patients with intersex abnormalities. Several reports document their ability to produce beta-human chorionic gonadotropin (HCG), but none have documented an elevated peripheral serum beta-HCG. We report on the case of a patient with pure gonadal dysgenesis with XY karyotype who was found to have an elevated peripheral serum beta-HCG after a positive pregnancy test. knowledge of gonadoblastoma's potential to elevate serum beta-HCG levels may prevent unnecessary searches for other causes. ( info) |
8/53. Identification of Y chromatin directly in gonadal tissue by fluorescence in situ hybridization (FISH): significance for Ullrich-turner syndrome screening in the cytogenetics laboratory. The presence of Y chromatin in individuals with Ullrich-turner syndrome (UTS) confers a risk for gonadoblastoma. In mosaic cases, little is known about Y chromatin distribution in gonads. fluorescence in situ hybridization (FISH) is a direct approach to assess the extent of Y chromatin mosaicism in gonads. Gonadal tissue from four patients with mosaic karyotypes were analyzed by routine cytogenetics and FISH with X and Y centromere probes. Y chromatin was present in gonads in varying percentages in these patients. The distribution of Y chromatin in gonads of UTS individuals did not completely correlate with that found in blood lymphocytes. The finding of Y chromatin in the blood samples from these patients prompted the development of a screening strategy in our cytogenetics laboratory to detect low-level Y chromatin mosaicism in patients with UTS. ( info) |
9/53. Ovarian gonadoblastoma with mixed germ cell tumor in a woman with 46, XX karyotype and successful pregnancies. An extremely rare case of unilateral gonadoblastoma with mixed germ cell tumor arising in the ovary of a 27-year-old woman with 46,XX karyotype and two successful pregnancies is reported. The mixed germ cell tumor was composed of choriocarcinoma, embryonal carcinoma, yolk sac tumor, immature teratoma and dysgerminoma. The patient has been well, without evidence of disease for over 10 years since her first surgery and adjuvant chemotherapy. ( info) |
10/53. 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. ( info) |