Service d'Anatomie Pathologique, Centre de Biologie et de Pathologie Est, Bron, France.
Université Lyon 1, Lyon, France.
Mod Pathol. 2016 Nov;29(11):1399-1414. doi: 10.1038/modpathol.2016.123. Epub 2016 Jul 29.
Disorders of sex development are defined as congenital conditions with discordance between the phenotype, the genotype, the karyotype, and the hormonal profile. The disorders of sex development consensus classification established in 2005 are mainly based on chromosomal and biological data. However, histological anomalies are not considered. The aims of this study were to define the specific pathological features of gonads in various groups of disorders of sex development in order to clarify the nosology of histological findings and to evaluate the tumor risk in case of a conservative approach. One hundred and seventy-five samples from 86 patients with disorders of sex development were analyzed following a strict histological reading protocol. The term 'gonadal dysgenesis' for the histological analysis was found confusing and therefore excluded. The concept of 'dysplasia' was subsequently introduced in order to describe the architectural disorganization of the gonad (various degrees of irregular seminiferous tubules, thin albuginea, fibrous interstitium). Five histological types were identified: normal gonad, hypoplastic testis, dysplastic testis, streak gonad, and ovotestis. The analysis showed an association between undifferentiated gonadal tissue, a potential precursor of gonadoblastoma, and dysplasia. Dysplasia and undifferentiated gonadal tissue were only encountered in cases of genetic or chromosomal abnormality ('dysgenesis' groups in the disorders of sex development consensus classification). 'Dysgenetic testes', related to an embryonic malformation of the gonad, have variable histological presentations, from normal to streak. Conversely, gonads associated with hormonal deficiencies always display a normal architecture. A loss of expression of AMH and α-inhibin was identified in dysplastic areas. Foci of abnormal expression of the CD117 and OCT4 immature germ cells markers in dysplasia and undifferentiated gonadal tissue were associated with an increased risk of neoplasia. This morphological analysis aims at clarifying the histological classification and gives an indication of tumor risk of gonads in disorders of sex development.
性发育障碍被定义为表型、基因型、核型和激素谱之间存在不一致的先天性疾病。2005 年建立的性发育障碍共识分类主要基于染色体和生物学数据。然而，组织学异常并未被考虑在内。本研究的目的是定义各种性发育障碍组中睾丸的特定病理特征，以阐明组织学发现的分类学，并评估保守治疗方法下的肿瘤风险。通过严格的组织学阅读方案分析了 86 例性发育障碍患者的 175 个样本。在组织学分析中，术语“性腺发育不良”被认为令人困惑，因此被排除。随后引入了“发育不良”的概念，以描述睾丸的结构紊乱（各种程度的不规则生精小管、薄白膜、纤维间质）。确定了五种组织学类型：正常睾丸、睾丸发育不全、睾丸发育不良、睾丸索和卵睾。分析表明，未分化性腺组织（性腺母细胞瘤的潜在前体）与发育不良之间存在关联。发育不良和未分化性腺组织仅在遗传或染色体异常的情况下出现（性发育障碍共识分类中的“发育不良”组）。与性腺胚胎畸形相关的“发育不良睾丸”具有不同的组织学表现，从正常到索状。相反，与激素缺乏相关的睾丸始终显示正常的结构。在发育不良区域中鉴定出 AMH 和α-抑制素的表达缺失。在发育不良和未分化性腺组织中异常表达 CD117 和 OCT4 未成熟生殖细胞标志物的病灶与肿瘤风险增加相关。这种形态学分析旨在阐明组织学分类，并提示性发育障碍中睾丸的肿瘤风险。
