True hermaphroditism (TH) refers to individuals who have both unequivocal ovarian tissue and testicular elements regardless of their karyotypes; whereas mixed gonadal dysgenesis (MGD) refers to individuals who usually have a differentiated gonad on one side and a streak gonad or streak testis on the other side. A differential diagnosis between the TH and MGD has important clinical implications for gender assignment and the decision for early gonadectomy; however, variable clinical and histological features frequently lead to the confusion of TH with MGD. We reviewed the clinicopathological features of TH (n = 4) and MGD (n = 6) in young children to identify which morphological features are important for a differential diagnosis between the two conditions. In both conditions, the testicular compartment was composed of immature seminiferous tubules lined by immature Sertoli cells and primitive germ cells; this finding was not helpful for a differential diagnosis. The ovarian compartment in TH cases showed numerous primordial follicles containing primary oocytes with a few primary or antral follicles; however, ovarian compartments in patients with MGD were characterized by primitive sex-cordlike structures with or without germ cell components within the ovarian-type stroma, mimicking gonadoblastomas in two cases and granulosa cell or Sertoli cell tumors in three cases. Hormonal profiles, cytogenetic results, and an internal duct system were not helpful in a differential diagnosis. In conclusion, a differential diagnosis between TH and MGD is largely dependent on the histological features of the gonads. Therefore, examination of all resected or biopsied tissue and the application of strict histological criteria are important.
There is much confusion about the nomenclature for patients with gonadal dysgenesis. Asymmetrical gonadal dysgenesis is the term used if one gonad displays more complete development and can be identified as an ovary or testis (usually testis), and the other gonad is a streak. Most patients with asymmetrical gonadal dysgenesis have testicular tissue on one side and a streak gonad on the other side. Some authors reserve the term mixed gonadal dysgenesis (MGD) for individuals who present a 45,X/46,XY karyotype with a testis on one side and a streak on the other side; other authors apply the term to all patients who have varying degrees of asymmetrical gonadal dysgenesis with testicular differentiation on either side, bilateral streak testis, or bilateral dysgenetic testis; in contrast, true hermaphroditism (TH) is the rarest form of intersexuality in humans, and the term is applied to an individual who has both well-developed ovarian and testicular tissues. A differential diagnosis between the two conditions has important clinical implications for gender assignment; furthermore, early gonadectomy in MGD patients is needed to prevent the development of malignant germ cell tumors. However, the form of intersexuality is sometimes very difficult to determine without a knowledge of normal histological findings of the gonads in newborns and young children. It is also true in adults, especially when both gonads are replaced by malignant tumors or when the gonads have various secondary histological changes. In young children, histological features of the gonads remain relatively unchanged, and they are helpful for understanding the histological differences between the TH and MGD.
Intersex, Mixed gonadal dysgenesis, True hermaphroditism