UCSF, San Francisco, CA, USA.
UCSF, San Francisco, CA, USA.
J Pediatr Urol. 2024 Oct;20(5):799-809. doi: 10.1016/j.jpurol.2023.12.016. Epub 2024 Jan 6.
The presence of an ovotestis is a rare difference of sex development. The diagnosis can be difficult with the gold standard being the presence of both testicular cords and ovarian follicles within the same gonad.
Herein we describe two new markers of ovotesticular syndrome: ovotesticular cords and ovotesticular follicles.
Twenty human gonads with a previous diagnosis of ovotestis were re-stained with markers for testicular cords (SOX9, TSPY, SALL4, DDX4, cP450, AR, α-actin) and ovarian tissue (FOXL2, SALL4, DDX4). Ovotesticular cords were defined as structures expressing both testicular Sertoli cell marker (SOX9) and an ovarian follicular cell marker (FOXL2), and in Y chromosome positive specimens, TSPY-positive testicular germ cells. Ovotesticular follicles were defined as a hybrid ovarian follicle containing FOXL2-positive granulosa cells and a central oocyte, but also containing cells expressing the testicular Sertoli cell marker, SOX9, intermingled within FOXL2-positive granulosa cells and male and female germ cells.
Six of twenty ovotestis did not meet our criterion for the diagnosis of ovotestis lacking the histologic evidence of both testicular and ovarian tissue. The remaining 13 patients in which 14 separate specimens were evaluated, contained ovotestis defined by the presence of testicular cords and ovarian follicles. Eleven of the 14 ovotestis specimens (79 %) contained ovotesticular cords. Four of 11 ovotestis specimens (36 %) contained ovotesticular follicles.
We recommend using eight immunohistochemical markers to diagnose an ovotestis: 1) SOX9, TSPY, SALL4, DDX4, cytochrome P450, AR, smooth muscle α-actin for the testicular component and FOXL2 and SALL4, DDX4 for the ovarian component. SOX9 and TSPY (useful only in the presence of a Y karyotype) are specific testicular markers and FOXL2 the only specific ovarian marker. We found ovotesticular cords and ovotesticular follicles in both human bipolar and mixed ovotestis specimens both with and without the presence of the Y chromosome. The clinical significance of ovotesticular cords and follicles remains unknown. We did not observe any obvious abnormalities in cellular architecture with the juxtaposition of testicular cells and ovarian cells.
We have identified two new structures in humans with ovotestis, ovotesticular cords and ovotesticular follicles (Figure), which appears to be additional markers to facilitate the diagnosis of ovotesticular gonads.
卵睾是一种罕见的性别发育差异。金标准是在同一个性腺中同时存在睾丸索和卵巢滤泡，因此诊断可能具有挑战性。
本文描述了卵睾综合征的两个新标志物：卵睾索和卵睾滤泡。
对 20 个人类性腺进行重新染色，以标记睾丸索（SOX9、TSPY、SALL4、DDX4、cP450、AR、α-肌动蛋白）和卵巢组织（FOXL2、SALL4、DDX4）。卵睾索被定义为表达睾丸支持细胞标记物（SOX9）和卵巢滤泡细胞标记物（FOXL2）的结构，并且在 Y 染色体阳性标本中，是 TSPY 阳性睾丸生殖细胞。卵睾滤泡被定义为一种混合性卵巢滤泡，包含 FOXL2 阳性颗粒细胞和中央卵母细胞，但也包含表达睾丸支持细胞标记物 SOX9 的细胞，这些细胞与 FOXL2 阳性颗粒细胞以及雄性和雌性生殖细胞混合在一起。
20 个卵睾中有 6 个不符合我们缺乏睾丸和卵巢组织组织学证据的卵睾诊断标准。在其余 13 名患者中，评估了 14 个单独的标本，其中包含存在睾丸索和卵巢滤泡的卵睾。14 个卵睾标本中的 11 个（79%）含有卵睾索。11 个卵睾标本中的 4 个（36%）含有卵睾滤泡。
我们建议使用 8 种免疫组织化学标志物来诊断卵睾：1）SOX9、TSPY、SALL4、DDX4、细胞色素 P450、AR、平滑肌α-肌动蛋白用于睾丸成分，FOXL2 和 SALL4、DDX4 用于卵巢成分。SOX9 和 TSPY（仅在存在 Y 染色体时有用）是特异性睾丸标记物，FOXL2 是唯一的特异性卵巢标记物。我们在具有和不具有 Y 染色体的人类双极和混合卵睾标本中均发现了卵睾索和卵睾滤泡。卵睾索和滤泡的临床意义尚不清楚。我们没有观察到睾丸细胞和卵巢细胞并置时细胞结构有任何明显异常。
我们在具有卵睾的人类中发现了两种新结构，卵睾索和卵睾滤泡（图），这似乎是有助于诊断卵睾性腺的附加标志物。
