RESUMEN

BACKGROUND: The aim of this study was to investigate the frequency of gonadal tumors among patients with Turner syndrome (TS) carrying Y-derivative sequences in their chromosomal constitution. METHODS: Six out of 260 patients with TS were selected based on mosaicism of the entire Y chromosome; 10 were included because Y-derivative sequences have been detected by PCR with specific oligonucleotides (sex-determining region on the Y, testis specific-protein, Y and DYZ3) and further confirmed by FISH. The 16 patients were subjected to bilateral gonadectomy at ages varying from 8.7 to 18.2 years. Both histopathological investigation with hematoxylin and eosin (H&E) and immunohistochemical analysis with anti-octamer-binding transcription factor 4 (OCT4) antibody were performed. RESULTS: Gonadal neoplasia was not detected in any of the 32 gonads evaluated by H&E; however, four gonads (12%) from three patients (19%) had positive OCT4 staining in 50-80% of nuclei, suggesting the existence of germ cell tumors (gonadoblastoma or in situ carcinoma). CONCLUSIONS: Evaluation of the real risk of development of gonadal tumors in TS patients with Y-derivative sequences in their chromosomal constitution may require a specific histopathological study, such as immunohistochemistry with OCT4.

Asunto(s)

Carcinoma in Situ/genética , Cromosomas Humanos Y/química , Gonadoblastoma/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Síndrome de Turner/genética , Adolescente , Carcinoma in Situ/complicaciones , Carcinoma in Situ/patología , Niño , Cromosomas Humanos Y/genética , Femenino , Gonadoblastoma/complicaciones , Gonadoblastoma/patología , Humanos , Inmunohistoquímica , Medición de Riesgo , Síndrome de Turner/complicaciones , Síndrome de Turner/patología

RESUMEN

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.

Asunto(s)

Gonadoblastoma/patología , Neoplasias Ováricas/patología , Adolescente , Femenino , Disgenesia Gonadal/complicaciones , Disgenesia Gonadal/patología , Gonadoblastoma/complicaciones , Gonadoblastoma/metabolismo , Humanos , Masculino , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/metabolismo , Adulto Joven

RESUMEN

Objetivo: Presentar un caso de gonadoblasgotoma bilateral y su manejo en una niña portadora de Síndrome de Tumer con antígeno SRY positivo Material y métodos: Niña de 6 años con el Síndrome de Tumer en cuyo cariotipo se encuentra un mosaicismo 45 XI SRY, con antígeno SRY positivo por lo que realiza estudio para descartar o confirmar la presencia de Gonadoblastoma consistente en Biopsia por laparoscopia de ambas gónadas. Resultados: Se encontró al estudio anatomo-patológico Gonadoblastoma bilateral, realizándose posteriormente gonadectomia bilateral, cuya evolución fue favorable. El Gonadoblastoma es un raro tumor compuesto por una combinación de células germinales y cor- dones sexuales-estroma que afecta exclusivamente a pacientes con disgenesia gonadal, siendo mas frecuente en niñas y adultas jóvenes fenotipicamente femeninas, que usual- mente tienen signos de virilización. Su . cuencia en gónadas disgenéticas es estimado en un 30 por ciento. Conclusión: Se recomienda la gonadecto-mía profiláctica en los casos de pacientescon síndrome Tumer con antígeno SRY positivo.

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Objectíve: To present a case of bilateral nadoblastoma and its management in a Tumer Síndrome girl with positive SRY antigen. Material and methods: A six-year-old girl who was diagnosed as Tumer Syndrome and her karyotype was 45 XI 46 XY, with positive antigen, then she was performed a 46 XY laparoscopic biopsy looking for gonadoblastoma. Results: We found histopathologic evidenences of bilateral Gonadoblastoma, and weperformed bilateral gonadectomy, and postoperative recovery was uneventful. Gonadoblastoma is an uncommon tumor which has germ cells, which affects to patients who were diagnosed as gonadal dysgenesis, it is more I frequent in children and young women phenotypically female, who used to have virilism signs. Its frequency in dysgenetic gonads is calculated in 30 percent. Conclusion: We suggest prophylactic gonadectomy in patients with Tumer Syndrome and evidence of y chromosome material.

Asunto(s)

Humanos , Femenino , Niño , Gonadoblastoma/cirugía , Gonadoblastoma/complicaciones , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/complicaciones , Síndrome de Turner/complicaciones , Biopsia , Cromosomas Humanos X , Cromosomas Humanos Y , Gonadoblastoma/genética , Gonadoblastoma/patología , Laparotomía , Mosaicismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Síndrome de Turner/genética , Resultado del Tratamiento

RESUMEN

UNLABELLED: The presence of Y chromosome fragments in patients with Turner's syndrome is known to increase the risk of gonadoblastoma and virilization. Y chromosome material is detected in up to 6% of patients with Turner's syndrome by karyotype. By DNA analysis, Y chromosome sequences have been reported in 0-60% of patients. The putative gonadoblastoma gene has been mapped to the pericentromeric region of the Y chromosome increasing the interest in studying these sequences. AIMS: 1. To determine the frequency of occult Y chromosome sequences in patients with Turner's syndrome. 2. To analyze the clinical implications of Y sequences detected by karyotype and occult Y sequences. STUDY DESIGN: Cross-sectional study of 58 patients with Turner's syndrome (30 45,X; two with structural anomalies; 26 mosaic [two of whom were 45,X/46,XY]). SRY, TSPY and DYZ3 sequences were amplified by PCR using genomic DNA from peripheral blood. RESULTS: All three Y chromosome sequences were found in one out of 56 patients whose karyotype was not suggestive of having Y chromosome material and in one patient with 45,X/46,Xr(X) karyotype. The patients with the ring chromosome and 45,X/46,XY karyotype underwent surgery and were found to have a gonadoblastoma and dysgerminoma. The four patients with Y chromosome material had non-virilized female genitalia. CONCLUSIONS: Analysis by PCR was more sensitive in detecting Y chromosome sequences than conventional karyotype. The presence of Y material was not associated with virilization. We confirmed the association of Y fragments and gonadoblastoma at an early age.

Asunto(s)

Cromosomas Humanos Y , Gonadoblastoma/complicaciones , Síndrome de Turner/complicaciones , Síndrome de Turner/genética , Virilismo/complicaciones , Adolescente , Adulto , Secuencia de Bases , Proteínas de Ciclo Celular , Niño , Preescolar , Chile , Estudios Transversales , Análisis Citogenético/métodos , Proteínas de Unión al ADN , Disgerminoma/complicaciones , Disgerminoma/diagnóstico , Disgerminoma/genética , Femenino , Gonadoblastoma/diagnóstico , Gonadoblastoma/genética , Gónadas/patología , Gónadas/cirugía , Gónadas/ultraestructura , Humanos , Cariotipificación , Linfocitos/citología , Mosaicismo , Proteínas Nucleares , Reacción en Cadena de la Polimerasa/métodos , Cromosomas en Anillo , Aberraciones Cromosómicas Sexuales , Proteína de la Región Y Determinante del Sexo , Factores de Tiempo , Factores de Transcripción , Síndrome de Turner/diagnóstico , Virilismo/diagnóstico

Asunto(s)

Disgenesia Gonadal 46 XY/complicaciones , Gonadoblastoma/complicaciones , Gonadoblastoma/patología , Seminoma/complicaciones , Seminoma/patología , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/patología , Síndrome de Turner/complicaciones , Disgenesia Gonadal 46 XY/cirugía , Gonadoblastoma/cirugía , Humanos , Lactante , Masculino , Seminoma/cirugía , Procesos de Determinación del Sexo , Neoplasias Testiculares/cirugía , Síndrome de Turner/cirugía

RESUMEN

OBJECTIVE: The frequency of Y-chromosome material is high in Turner syndrome (TS), but the ocurrence of gonadoblastoma seems to be low. We performed a study to evaluate whether DNA analysis might be a useful tool in the evaluation of patients with TS. SUBJECTS: Unrelated patients with TS (n = 52) of Venezuelan mestizo ethnic origin were diagnosed by cytogenetic analysis as having TS. METHODS: Clinical assessment, karyotyping, endocrine evaluation, fluorescence in situ hybridization, and polymerase reaction chain analysis of the Y-chromosome loci. RESULTS: We found that 7.69% (4 of 52) patients with TS had Y-chromosome material. A low occurrence of gonadoblastoma was also found (2 of 52 [3.85%]). Two patients showed a 45,X/46,XY karyotype, and gonadoblastoma in the gonadal biopsy specimen was not found. Two patients had no Y chromosome on initial karyotype; they were positive on lymphocyte DNA to Y-sequences specific. Both patients (45,X) had bilateral gonadoblastoma. The four patients with Y-chromosome material in peripheral blood lymphocytes had Y-chromosome sequences on gonadal DNA. Fluorescence in situ hybridization confirmed their Y-chromosome origin. CONCLUSIONS: Our results suggest that the detection of Y-chromosome material should be carried out in all patients with TS and not be limited to patients with TS with cytogenetically identifiable Y chromosome and/or virilization.

Asunto(s)

Cromosomas Humanos Y/genética , Síndrome de Turner/genética , Niño , Análisis Citogenético , Femenino , Gonadoblastoma/complicaciones , Gonadoblastoma/genética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Mosaicismo , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/genética , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Síndrome de Turner/complicaciones , Síndrome de Turner/diagnóstico

RESUMEN

Introducción: la presencia de material del cromosoma Y en mujeres con Síndrome de Turner se asocia con el desarrollo de tumores gonadales, teniendo un incremento del riesgo relacionado con la edad. Objetivo: investigar la correlación entre la presencia de cromosoma Y ó secuencias específicas del Y y los hallazgos histopatológicos de las gónadas en pacientes con Síndrome de Turner. Material y métodos: se estudiaron cinco niñas con síndrome de Turner, con edades comprendidas entre los 4.4 y 13.4 años de edad. En todas las pacientes se realizó el análisis cromosómico con bandeo G y técnicas de alta resolución, tales como análisis molecular por PCR amplificando las secuencias específicas del cromosoma Y (SRT, DYZ1, DYZ3 y AMGL). Tres niñas tenían un cariotipo conteniendo el cromosoma Y, mientras que en las otras dos niñas restantes fueron detectadas secuencias del cromosoma Y por análisis molecular. En todas la niñas fue realizada la gonadectomía bilateral con técnica laparoscópica. Resultados: el procedimiento laparoscópico fue adecuado y bien tolerado por las niñas. Tres de las pacientes (de 5.4, 8 y 13.4 años de edad) que tenían cromosoma Y presentaron tumores gonadales: gonadoblastoma uni o bilateral, y en una de ellas se encontró un disgerminoma. En las dos niñas restantes se encontraron las típicas gónadas tipo "streak" del Síndrome de Turner, sin tejido neoplásico. Conclusión: el hallazgo de tumores gonadales en 3 de las 5 niñas con Síndrome de Turner refuerza la importancia de la indicación de la gonadectomía a edades tempranas cuando las pacientes son portadoras de material del Y en sus cromosomas. La técnica laparoscópica es una elección adecuada para el tratamiento (AU)

Asunto(s)

Humanos , Femenino , Preescolar , Síndrome de Turner/complicaciones , Gonadoblastoma/complicaciones , Germinoma/complicaciones , Síndrome de Turner/cirugía , Síndrome de Turner/genética , Cromosoma Y , Mosaicismo , Gonadoblastoma/etiología , Gonadoblastoma/prevención & control , Germinoma/etiología , Germinoma/prevención & control , Ovario/cirugía , Gónadas/cirugía

RESUMEN

Cytogenetic studies of normal and tumor cells in a patient with gonadal dysgenesis and bilateral gonadoblastoma were performed. The karyotype was 46,XY in peripheral blood lymphocytes and skin fibroblasts. The conserved region of the SRY gene was detected by polymerase chain reaction amplification. Sequencing of this region did not reveal any alterations. A 46,XY chromosome constitution was observed in the right gonadoblastoma, but a partial deletion of chromosome 13 was present in the left tumor. This deletion included band 13q14, where the retinoblastoma gene is mapped. The study of the polymorphism of the variable number of tandem repeats region in intron 17 of the RB1 locus disclosed loss of heterozygosity in both the left tumor, which showed the deletion of chromosome 13, and in the right tumor, where no chromosome alterations of chromosome 13 were detected. In situ hybridization covering 130 kb of RB1 showed that a partial deletion of one of the RB1 alleles had occurred in the right tumor. Since the deletions affected different alleles in each tumor, independent events must have been involved in the development of the tumors. These findings point toward a significant role of RB1 in the development of gonadoblastoma.

Asunto(s)

Eliminación de Gen , Genes de Retinoblastoma , Disgenesia Gonadal 46 XY/genética , Gonadoblastoma/genética , Adolescente , Bandeo Cromosómico , Cromosomas Humanos Par 13 , Exones , Femenino , Disgenesia Gonadal 46 XY/complicaciones , Gonadoblastoma/complicaciones , Humanos , Hibridación Fluorescente in Situ , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN

RESUMEN

This paper reports a case of XY gonadal dysgenesis in two sisters. Both patients presented an eunochoid female phenotype with normal external genitalia. At laparotomy, the elder sister was found to have bilateral gonadoblastoma. Cytogenetic studies, which included G and C banding and in situ hybridization, showed that the patients had an apparently normal 46, XY karyotype. PCR analyses revealed absence of the conserved portion (HMG box) of the SRY gene and of the Y chromosome pseudoautosomal boundary region sequence in both patients. The presence of the ZFY sequence was detected by Southern hybridization in the two affected sisters. The patients' father (46, XY, no mosaicism detected in peripheral blood lymphocytes) was positive for SRY and ZFY sequences. The occurrence of gonadoblastoma is discussed in terms of the genetic factors that may lead to tumor development.

Asunto(s)

Deleción Cromosómica , Proteínas de Unión al ADN/genética , Disgenesia Gonadal 46 XY/genética , Gonadoblastoma/genética , Proteínas Nucleares , Neoplasias Ováricas/genética , Factores de Transcripción , Cromosoma Y , Adolescente , Adulto , Secuencia de Bases , Cartilla de ADN , Femenino , Disgenesia Gonadal 46 XY/complicaciones , Gonadoblastoma/complicaciones , Humanos , Datos de Secuencia Molecular , Neoplasias Ováricas/complicaciones , Proteína de la Región Y Determinante del Sexo