Spoor Johannes A, Oosterhuis J Wolter, Hersmus Remko, Biermann Katharina, Wolffenbuttel Katja P, Cools Martine, Kazmi Zainab, Ahmed Syed F, Looijenga Leendert H J
Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, UK.
Sex Dev. 2018;12(1-3):106-122. doi: 10.1159/000481757. Epub 2017 Nov 3.
Malignant gonadal germ cell tumors, referred to as germ cell cancers (GCC), occur with increased frequency in individuals who have specific types of differences (disorders) of sex development (DSD). Recent population-based studies have identified new environmental and genetic risk factors that have led to a 'genvironment' hypothesis, which may potentially be helpful in risk assessment in DSD-related GCC. In DSD, the malignancy risk is highly heterogeneous, but recent studies allow now to discriminate between high- and low-risk conditions. Gonadal biopsy is in some cases the best procedure of choice to assess the risk, and with the availability of immunohistochemical biomarkers [OCT3/4 (POU5F1), TSPY, SOX9, FOXL2 and KITLG (SCF)], a reliable classification of GCC and its precursors can be made. The opportunities in the field of virtual diagnostic pathology will be presented, having possibilities for rare diseases in general and DSD specifically. It is expected that the International DSD Registry will stimulate international collaborations, facilitating better diagnostic procedures as well as research.
恶性性腺生殖细胞肿瘤，称为生殖细胞癌（GCC），在患有特定类型性发育差异（DSD）的个体中发生频率增加。最近基于人群的研究已经确定了新的环境和遗传风险因素，这导致了一种“环境”假说，这可能有助于DSD相关GCC的风险评估。在DSD中，恶性风险高度异质，但最近的研究现在可以区分高风险和低风险情况。在某些情况下，性腺活检是评估风险的最佳选择程序，并且有了免疫组化生物标志物[OCT3/4（POU5F1）、TSPY、SOX9、FOXL2和KITLG（SCF）]，可以对GCC及其前体进行可靠分类。将介绍虚拟诊断病理学领域的机会，这对一般罕见疾病特别是DSD具有可能性。预计国际DSD登记处将促进国际合作，推动更好的诊断程序以及研究。
