Morphometry and Histology of Gonads From 13 Children With Dysgenetic Male Pseudohermaphroditism

Abstract

Background.—Dysgenetic male pseudohermaphroditism (DMP) is a sexual differentiation disorder characterized by bilateral dysgenetic testes, persistent müllerian structures, and cryptorchidism in individuals with a 46,XY karyotype. However, the histologic criteria for the diagnosis of DMP are poorly established. Objective.—To determine gonadal histology in children with DMP. Patients and Methods.—Between 1996 and 1998, 13 patients with DMP were evaluated on our service. The clinical diagnosis of DMP was based on a 46,XY karyotype, sex ambiguity, high levels of follicle-stimulating hormone and low levels of antimüllerian hormone, a decreased testosterone response to human chorionic gonadotropin stimulation without accumulation of testosterone precursors, and the presence of müllerian structures. Molecular sequencing the HMGbox region of the SRY gene did not reveal any mutations. Biopsies were performed for 22 of 26 gonads (patient age at the time of biopsy, 16 months to 10 years). Conventional microscopy was used to evaluate mean tubular diameter, tubular fertility index, and number of Sertoli cells per tubular profile. Results.—All 26 gonads were located outside of the labioscrotal folds. Their histologic features varied from only a reduction in tubular size to features of a streak gonad. Five of the 22 gonads grossly resembled a streak gonad. The mean tubular diameter was severely reduced (>30% reduction relative to the normal tubular diameter for the patient's age) in 4 gonads, markedly reduced (10%–30%) in 11 gonads, slightly reduced (<10%) in one gonad, and normal in one gonad. The tubular fertililty index, expressed as the percentage of tubular profiles containing germ cells, was severely reduced (<30% of normal values) in 9 gonads, markedly reduced (50%–30%) in 2 gonads, and normal in 6 gonads. The number of Sertoli cells per tubular profile was elevated in 16 gonads and normal in one gonad. Thin tubules surrounded by fibrous tissue were occasionally observed. Conclusion.—The histologic findings confirmed the clinical diagnosis of DMP in every patient in the present series. However, gonadal histology was variable, and careful morphometric evaluation may be necessary to establish the diagnosis.

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“…273 Mullerian ducts remnants are seen frequently in 46,XY DSD and 46,XY gonadal dysgenesis. 274,275 Androgen insensitivity syndrome (AIS) is a heterogeneous group of defects in the androgen receptor, resulting in varying degrees of defective masculinization in 46,XY individuals. Ambiguous genitalia in 46,XX females is caused by early antenatal exposure to androgen from fetal adrenals, fetal aromatase deficiency, maternal androgen-producing tumors, maternal exogenous androgen exposure, WNT4 mutation, or as associations.…”

Diagnóstico de 408 casos de ambiguidade genital acompanhados por uma única equipe interdisciplinar durante 23 anos

“…Com as novas técnicas de sequenciamente genômico, novos genes estão surgindo como candidatos a participarem deste complexo processo da formação da gônada (5,8,74). Os DDG incluem um grupo de doenças no qual a formação da gônada foi inadequada ou não ocorreu de forma completa, sendo, portanto diagnósticos que exigem a confirmação histológica e a experiência de um patologista teinado na área (75). Como são doenças que podem estar associadas às anormalidades cromossômicas e gênicas, também se faz necessário ter avaliação laboratorial com citogenética convencional, citogenética molecular e molecular de qualidade (76) (77,78), e no NR5A1 pelo risco de insuficiência adrenal e falência ovariana primária em mulheres afetadas (80)(81)(82).…”