RESUMEN
All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an in situ stage (CIS) of protracted evolution. The adult CIS is well characterized, but there is debate on the phenotype of infantile CIS, its distinction from delayed maturation of germ cells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD) and dysgenetic testes (90% ranging from neonates to 12 years, mean age 4.7 years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA), expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy and evolution to CIS and invasive TGCT. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients: bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for combined, n = 13), and ovarian-testicular combinations (OT-DSD, n = 9). There were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two patients with adult CIS, bilateral in one (total of 3 adult CIS). Two patients had bilateral seminomas one at 12-17 and the other at 23 years. Histological dysgenesis was significantly higher in CT-DSD (p < 0.05), that had only 1 CIS. The highest frequency of GCA was in BT-DSD (p < 0.05), which coincided with a total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy (p < 0.02), and GCA were more frequent in aneuploid than in diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive. Finally, there was a significant association between the triad Aneuploidy + GCA + OCT 3/4 positivity and the incidence of CIS (Fisher Exact test p < 0.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetal testicular cords) is inversely related to the incidence of CIS. Our data demonstrate that the combined use of OCT 3/4 expression, quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS with high risk of malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma in Situ/genética , Disgenesia Gonadal/genética , Seminoma/genética , Desarrollo Sexual/genética , Neoplasias Testiculares/genética , Adolescente , Argentina/epidemiología , Carcinoma in Situ/química , Carcinoma in Situ/epidemiología , Carcinoma in Situ/patología , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Disgenesia Gonadal/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Factor 3 de Transcripción de Unión a Octámeros/análisis , Fenotipo , Ploidias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Seminoma/química , Seminoma/epidemiología , Seminoma/patología , Neoplasias Testiculares/química , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/patología , Adulto JovenRESUMEN
OBJECTIVE: To determine the frequency of XY karyotypes among females with complete gonadal dysgenesis (CGD) and to investigate the frequency of both gonadal tumors and SRY mutations. DESIGN: Retrospective study based on data from all patients with CGD seen in our service from 1989 to 2010. SETTING: Clinic for disorders of sex development, University Hospital, State University of Campinas. PATIENT(S): Thirty-two patients with hypergonadotropic hypogonadism, streak gonads, internal and external female genitalia, and normal karyotype (46,XX or 46,XY); 31 were index cases and 29 did not have a previously determined karyotype. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): The percentage of XY karyotypes among patients with CGD was 34.5% (10/29). Mean age at diagnosis among XY and XX patients was 17.4 years and 19.9 years, respectively. Gonadal tumors were found in 4 of 9 XY girls, and 7 of 10 had SRY gene mutations. CONCLUSION(S): The previously unreported finding of an elevated frequency of 46,XY karyotype among patients with CGD and the high risk of gonadal neoplasia in such cases indicate that this diagnosis must be kept in mind by clinicians and strengthen the importance of karyotype analysis in females with primary hypogonadism. In addition, the frequency of SRY mutations in XY CGD might be higher than previously considered.
Asunto(s)
Disgenesia Gonadal 46 XY/epidemiología , Disgenesia Gonadal/epidemiología , Adolescente , Adulto , Edad de Inicio , Niño , Femenino , Genes sry , Disgenesia Gonadal/clasificación , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/genética , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/genética , Humanos , Cariotipo , Práctica Profesional/estadística & datos numéricos , Estudios Retrospectivos , Adulto JovenRESUMEN
Se reportan las manifestaciones esqueléticas con traducción radiológica de 27 pacientes menores de 15 años de edad portadores de disgenesia gonodal con fenotipo femenino, estudiados en el Instituto de Endocrinología y Enfermedades Metabólicas, entre febrero de 1965 y diciembre de 1970. Se pone de manifiesto la alta incidencia de estas afecciones, comentándose su etiología, la que parece estar más en relación con un patrón propio determinado genéticamente, que con los trastornos de tipo endocrino que se asocian a esta entidad(AU)