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.1255652656Robboy, S.J., Miller, T., Donahoe, P.K., Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: Perspective derived from clinicopathologic analysis of twenty-one cases (1982) Hum Pathol, 13, pp. 700-716Troche, V., Hernandez, E., Neoplasia arising in dysgenetic gonads (1986) Obstet Gynecol Surv, 41, pp. 74-79Krasna, I.H., Lee, M.L., Smilow, P., Sciorra, L., Eierman, L., Risk of malignancy in bilateral streak gonads: The role of the Y chromosome (1992) J Pediatr Surg, 27, pp. 1376-1380Rohatgi, M., Gupta, D.K., Menon, P.S., Verma, I.C., Mathur, M., Mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism - A critical analysis (1992) Indian J Pediatr, 59, pp. 487-500Rey, R.A., Belville, C., Nhou-Fékété, C., Evaluation of gonadal function in 107 intersex patients by means of serum antimüllerian hormone measurement (1999) J Clin Endocrinol Metab, 84, pp. 627-631Stuchi-Perez, E.G., Lukas-Croisier, C., Castro, M., Evaluation of the tubular and interstitial functions of the testis in 46,XY patients with ambiguous genitalia (2000) J Pediatr Endocrinol Metab, 13, pp. 605-612Chang, H.J., Clark, R.D., Bachman, H., The phenotype of 45,X/46,XY mosaicism: An analysis of 92 prenatally diagnosed cases (1990) Am J Hum Genet, 46, pp. 156-167Rajfer, J., Walsh, P.C., Mixed gonadal dysgenesis: Dysgenetic male pseudoher-maphroditism (1981) The Intersex Child: Pediatric and Adolescent Endocrinology, pp. 103-115. , Josso N, ed. Basel, Switzerland: S. KargerBorer, J.G., Nitti, V.W., Glassberg, K.I., Mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism (1995) J Urol, 153, pp. 1267-1273Donahoe, P.K., Crawford, J.D., Hendren, W.H., Mixed gonadal dysgenesis: Pathogenesis and management (1979) J Pediatr Surg, 14, pp. 287-300Pelletier, J., Bruening, W., Kashtan, C.E., Germline mutations in the Wilms' tumor supressor gene are associated with abnormal urogenital development in Denys-Drash syndrome (1991) Cell, 67, pp. 437-1147Carré-Éusebe, D., Imbeaud, S., Harbison, M., New, M.I., Josso, N., Picard, J.Y., Variants of the anti-Müllerian hormone gene in a compound heterozygote with the persistent Müllerian duct syndrome and his family (1992) Hum Genet, 90, pp. 389-394Nistal, M., Paniagua, R., Non-neoplastic diseases of the testis (1996) Urologic Surgical Pathology, pp. 458-565. , Bostiwick DG, Eble JN, eds. St Louis, Mo: MosbyLennox, B., Ahmad, K.M., Mack, W.S., A method for determining the relative total length of the tubules in the testis (1970) J Pathol, 102, pp. 229-238Jimenez, R., Sanchez, A., Burgos, M., Dias De La Guardia, R.C., Puzzling out the genetics of mammalian sex determination (1996) Trends Genet, 12, pp. 164-166Müller, J., Skakkebaek, N.F., Quantification of germ cells and seminiferous tubules by stereological examination of testicles from 50 boys who suffered from sudden death (1983) Int J Androl, 6, pp. 143-156Cortes, D., Müller, J., Skakkebaek, N.E., Proliferation of Sertoli cells during development of the human testis assessed by stereological methods (1987) Int J Androl, 10, pp. 589-596Nistal, M., Abaurrea, M.A., Paniagua, R., Morphological and histometric study on the human Sertoli cell from birth to the onset of puberty (1982) J Anat, 14, pp. 351-363Van Niekerk, W.A., Retief, A.E., The gonads of human true hermaphrodites (1981) Hum Genet, 58, pp. 117-122Guerra Jr., G., De Mello, M.P., Assumpção, J.G., True hermaphrodites in the southeastern region of Brazil: A different cytogenetic and gonadal profile (1998) J Pediatr Endocrinol Metab, 11, pp. 519-524Quigley, C.A., De Bellis, A., Marschke, K.B., El-Awady, M.K., Wilson, E.M., French, F.S., Androgen receptor defects: Historical, clinical and molecular perspectives (1995) Endocr Rev, 16, pp. 271-321