Morphometry and histology of gonads from 13 children with dysgenetic male pseudohermaphroditism

Background.-Dysgenetic male pseudohermaphroditism (DMP) is a sexual differe ntiation disorder characterized by bilateral dysgenetic testes, persistent mullerian structures, and cryptorchidism in individuals with a 46,XY karyot ype. However, the histologic criteria for the diagnosis of DMP are poorly e stablished. Objective.-To determine gonadal histology in children with DMP. Patients and Methods.-Between 1996 and 1998, 13 patients with DMP were eval uated on our service. The clinical diagnosis of DMP was based on a 46,XY ka ryotype, sex ambiguity, high levels of follicle-stimulating hormone and low levels of antimullerian hormone, a decreased testosterone response to huma n chorionic gonadotropin stimulation without accumulation of testosterone p recursors, and the presence of mullerian structures. Molecular sequencing t he HMGbox region of the SRY gene did not reveal any mutations. Biopsies wer e performed for 22 of 26 gonads (patient age at the time of biopsy, 16 mont hs 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. Thei r histologic features varied from only a reduction in tubular size to featu res of a streak gonad. Five of the 22 gonads grossly resembled a streak gon ad. The mean tubular diameter was severely reduced (>30% reduction relative to the normal tubular diameter for the patient's age) in 4 gonads, markedl y reduced (10%-30%) in 11 gonads, slightly reduced (<10%) in one gonad, and normal in one gonad. The tubular fertility index, expressed as the percent age of tubular profiles containing germ cells, was severely reduced (<30% o f normal values) in 9 gonads, markedly reduced (50%-30%) in 2 gonads, and n ormal in 6 gonads. The number of Sertoli cells per tubular profile was elev ated in 16 gonads and normal in one gonad. Thin tubules surrounded by fibro us 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 var iable, and careful morphometric evaluation may be necessary to establish th e diagnosis.