Prevalence, distribution, and risk markers for the development of gonadal germ cell tumors in patients with certain types of disorders of sexual differentiation with Y chromosome - A retrospective study.

PURPOSE: To study the prevalence, subtypes, and risk markers for the development of gonadal germ cell tumors (GCT's) among disorders of sexual differentiation (DSD) patients with the Y chromosome. MATERIALS AND METHOD: Design: A retrospective review of the patient's case records from 2010 to 2020 in Government Medical College, Thiruvananthapuram, India was studied. The study participants included 54 subjects with DSD containing the Y chromosome. Demographic data, external masculinization scoring, associated congenital anomalies, karyotyping, intraoperative findings such as gonadal location and internal genital ducts, histopathology of the resected gonads, and its immunohistochemistry were collected. The prevalence of gonadal GCT's was estimated from paraffin-embedded gonadectomy samples (S = 82). RESULTS: The median age of occurrence of gonadal GCT's was 18 years. The prevalence of malignant gonadal GCT's was highest among the PAIS group (19.2%) followed by gonadal dysgenesis (15.8% each in MGD and CGD) and least among CAIS (7.7%) (p < 0.01). The most common type of malignant gonadal GCT's in the descending order of frequency was dysgerminoma, seminoma, mixed GCT, and yolk sac tumor. Multivariance logistic analysis showed post-puberty and the presence of congenital anomalies were associated with the occurrence of gonadal GCT's ( P < 0.01). CONCLUSION: The overall prevalence of gonadal GCT's (malignant and premalignant) among DSD with Y chromosomes is nearly 25%. Dysgerminoma is the most common malignant gonadal GCT's. Age at or above 18 years and the presence of congenital anomalies like renal agenesis, retroperitoneal vascular defects, and congenital diaphragmatic hernia were independent risk markers for the development of gonadal GCT's.

Gonadal tumor and malignancy in 118 patients with disorders of sex development with Y chromosome.

OBJECTIVE: To provide more information about tumor prevalence and malignant transformation among patients with disorders of sex development (DSD) for further guidance in prophylactic gonadectomies and surveillance. METHODS: SPSS software (version 20.0) was used for all statistical analyses. RESULTS: Phenotypically female DSD patients with a Y chromosome have a higher risk of gonadal malignancy. CONCLUSION: Bilateral gonadal resection is recommended as soon as diagnosis is made for phenotypically female patients with disorders of sex development with a Y chromosome.

Microdeleçöes do cromossoma Y em homens azoospérmicos e oligoospérmicos severos / Y-Chromosome microdeletions in azoospermic and severel oligozoospermic men

O fator masculino é responsável por aproximadamente metade dos casos de infertilidade do casal. Em mais de 60 por cento dos casos a origem da funçäo testicular diminuída näo é conhecida, podendo haver muitas anomalias genéticas näo identificadas. Microdeleçöes do braço longo do cromossoma Y säo associadas com falência da espermatogênese e tem sido usado para definir três regiöes do Yq (AZFa, AZFb e AZFc) que estäo correntemente deletados em homens inférteis. Em torno de 10 a 15 por cento dos azoospérmicos e 5 a 10 por cento dos homens severemente oligospérmicos tem microdeleçöes do Yq. Técnicas de reproduçäo assistida, principalmente Injeçäo Intra Citoplasmática de Esperma em associaçäo com retirada de esperma testicular, representam uma eficiente terapia para estes pacientes. Os autores fazem uma revisäo atual das microdeleçöes do cromossoma Y e suas conseqüências na fertilidade masculina.

Infertile couples with Robertsonian translocations: preimplantation genetic analysis of embryos reveals chaotic cleavage divisions.

Preimplantation genetic diagnosis (PGD) may provide a feasible option for some Robertsonian translocation carriers who experience severe difficulty in achieving a normal pregnancy. We report on five PGD cycles for two such couples, 45,XY,der(13;14)(q10:q10) and 45,XX,der(13;21)(q10;q10), carried out by biopsy of two cells from day 3 post-insemination embryos generated by in vitro fertilisation. Locus-specific YAC probes for chromosomes 13, 14 and 21 were used to detect the chromosomes involved in the translocation using multicolour FISH. Three embryos transfers were carried out (two single embryo transfers and one double transfer) but no clinical pregnancies were established. In two cycles no embryos were transferred as all those biopsied were chromosomally abnormal. Combined results from both couples show 13% (6/45) of embryos analysed were normal for the translocation chromosomes and 87% (39/45) were chromosomally abnormal; these were categorised as 36% aneuploid or aneuploid mosaic and 51% chaotic where the chromosome constitution varied randomly from cell to cell. This suggests two factors may be acting to reduce fertility in these couples; the aneuploid segregation of the parental Robertsonian translocation and also a post-zygotic factor leading to uncontrolled chromosome distribution in early cleavage stages in an exceptionally high proportion of embryos.

[Undescended testis and hypospadia in sex chromosomal aberrations]. / Maldescensus testis und Hypospadie bei Aberration der Geschlechtschromosomen.

If hermaphrodite genitals are present in the patient or a higher degree of hypospadia is shown with maldescensus testis, a chromosomal disorder must be considered as one potential cause of the anomaly. The case report of a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadia is presented as an example. A mosaic karyotype 45, X/46, X, idic (Yp) was diagnosed in this patient after chromosomal analysis. The cell line with the isodicentric Y chromosome could be demonstrated in about 90% of the lymphocytes, but only in 7% of the fibroblasts of the preputium. A derivative Y could not be detected in interphase nuclei in the buccal mucosa, i.e. only the cell line with monosomy X was presented. There was thus chromosomal mosaicism with unequal tissue involvement and a high potential for malignant transformation. Guidelines of pediatric urological, cytogenetic and endocrinological investigations and the diagnostic procedures are described and discussed. A prevention protocol for patients with comparable gonosomal mosaicism is presented.

Gonadoblastomas in 45,X/46,XY mosaicism: analysis of Y chromosome distribution by fluorescence in situ hybridization.

Gonadoblastomas are composed of nests of neoplastic germ cells and sex cord derivatives surrounded by ovarian-type stroma. These tumors are found almost exclusively in persons with gonadal dysgenesis associated with a Y chromosome or Y chromosome fragment, and accordingly, the Y chromosome has been implicated in gonadoblastoma oncogenesis. To evaluate this association, we used two-color fluorescence in situ hybridization with chromosome-specific probes to determine the distribution of the X and Y chromosomes in the tumor nests and surrounding stromal cells in paraffin tissue sections of three gonadoblastomas in two patients with gonadal dysgenesis and 45,X/46,XY mosaicism. Statistical analysis of the data from the fluorescence in situ hybridization demonstrated that in all three gonadoblastomas, the proportion of nuclei with a Y chromosome signal was significantly higher in the tumor cells than in the nontumoral cells of the surrounding stroma (P<.001). These results suggest that Y chromosome material participates in gonadoblastoma tumorigenesis.

Ambiguous genitalia in an elderly woman with a mosaic 45,X/46,X,dic(Y)(Q11.2) karyotype.

A 66-year-old woman presented with clitoromegaly since childhood, primary amenorrhea, no breast development, and a large right inguinal hernia. A mosaic karyotype was identified containing a predominant 45,X cell line and a cell line with 46 chromosomes, one X chromosome, and a small dicentric Y chromosome with a breakpoint in band qII.2. The patient underwent hysterectomy, bilateral gonadectomy, inguinal hernia repair, clitoral recession, and formation of a neointroitus. A dysgerminoma was identified in the right dysgenetic gonad. This report demonstrates the natural history of untreated mixed gonadal dysgenesis and the importance of early evaluation and treatment, as well as the molecular characterization of a dicentric Y chromosome.

Genotypic analysis of primary head and neck squamous carcinoma by combined fluorescence in situ hybridization and DNA flow cytometry.

Concurrent DNA flow cytometric (FCM) and fluorescence in situ hybridization (FISH) analyses were prospectively performed on 24 primary untreated head and neck squamous carcinomas for characterization of the genotypic and phenotypic DNA aberrations of these neoplasms. Eleven tumors (42.0%) manifested DNA diploidy (DI = 1.00) and 15 (58.0%) had DNA aneuploidy (DI < or > 1.00) by FCM. Fluorescence in situ hybridization results showed aneusomy in the majority of DNA diploid and in all DNA aneuploid tumors. The extent of the abnormalities for individual chromosomes and the number of involved chromosomes in a given DNA diploid or aneuploid tumor were significantly different. Overall, a statistical correlation between the FCM DNA index (DI) and the magnitude of the chromosomal aberration by FISH was found. Our results also show a significant association between the DI and histologic differentiation and stage of disease in these neoplasms. In conclusion, (1) chromosomal aneusomy characterizes most DNA diploid (DI = 1.00) and all DNA aneuploid (DI < or > 1.00) head and neck squamous carcinomas; (2) polysomy is the most prevalent finding; (3) loss of the Y chromosome in tumors from male patients is a consistent feature; (4) the FCM DI reflects net chromosomal gains or losses in these neoplasms; and (5) DNA aneuploidy is associated with tumor aggressiveness.

Etiología cromosómica de la esterilidad e infertilidad masculina / Chromosomic etiology of masculine sterility and infertility

Avances recientes en el conociminto del desarorollo sexual se han logrado al estudiar individuos con gónadas disgenéticas y alteraciones del aparato reproductor. Utilizando sondas Y-ADN en estos pacientes se ha encontrado que un gen de los brazos cortos del cromosoma Y, induce la diferenciación testicular. La forma como este gen actúa no se conoce, pero la observación de que existen secuencias homólogas en X y Y sugiere la posibilidad de que la diferenciación sexual depende de dosis génicas. Otros genes como el que codifica para el antígeno H-Y, el de la maduración esquelética, el crecimietno corporal, el tamaño dental y la regulación de la espermatogénesis se han identificado en el cromosoma Y. Hallazgos que han permitido un mejor entendimiento de los factores genéticos y citogénicos involucrados en la esterilidad-infertilidad.

Molecular scanning of Yq11 (interval 6) in men with Sertoli-cell-only syndrome.

Data suggesting that probes pDP105/B and 50f2/C,E may identify sequences on distal Yq11 (interval 6) that are critical for spermatogenesis stimulated a study of this region by means of these two probes in azoospermic 46,XY men with biopsy-proved Sertoli-cell-only syndrome. Deoxyribonucleic acid samples from controls and study subjects were digested with the restriction enzymes TaqI, EcoRI, and BamHI. These samples were blotted and hybridized with pDP105/B, 50f2/C,E, and two more proximal Yq11 probes 4B-2 and pAS1. The sequence hydridizing to 50f2/C was absent in one study subject. No deletions were detected with pDP105/B and the two more proximal probes.

Turner syndrome resulting from partial deletion of Y chromosome short arm: localization of male determinants.

Chromosome studies performed because of the possibility of Turner syndrome in an infant girl with pedal edema and mild neck webbing revealed an XY karyotype. Subsequent exploratory laparotomy showed dysplastic ovaries with nests of germ cells with the morphologic features of gonadoblastoma. Repeat chromosome studies from peripheral blood using high-resolution techniques, and also from skin and ovarian fibroblasts, showed an XY karyotype but with a partial deletion of the Y short arm, which was not detected with standard techniques. These findings indicate that testis determining factors are located in this deleted region of the Y chromosome but that other gene(s) remain that induce gonadoblastoma.

[Sex chromatin in oncomorphology]. / Polovoi khromatin v onkomorfologii.

SCr body is a label of repression of one of the sex chromosomes (X chromosome in women or Y chromosome in men) in the interphase nucleus. By the end of the synthesis period these chromosomes undergo derepression since DNA replication occurs. Thus, by the end of the synthetic and in premitotic periods of the cellular cycle the SCr body disappears. In tumors of various locations, a clear-cut inverse proportional dependence between a decrease in the number of nuclei with SCr bodies and an increase in the mitotic index was demonstrated. Therefore, the CSr test is an index of the growth rate (proliferative activity) of the examined tumor. By this test it is possible to determine the degree of the tumor progression, to assess the mitotic activity in small pieces of biopsy materials. The SCr test may be an additional method for differential diagnosis of malignant tumors.