Looijenga Leendert H J
Department of Pathology, Erasmus MC-Erasmus University Medical Center, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Rotterdam, The Netherlands.
J Pathol. 2009 Jun;218(2):146-62. doi: 10.1002/path.2522.
Human germ cell tumours (GCTs) comprise several types of neoplasias with different pathogeneses and clinical behaviours. A classification into five subtypes has been proposed. Here, the so-called type II testicular GCTs (TGCTs), ie the seminomas and non-seminomas, will be reviewed with emphasis on pathogenesis and clinical implications. Various risk factors have been identified that define subpopulations of men who are amenable to early diagnosis. TGCTs are omnipotent, able to generate all differentiation lineages, both embryonic and extra-embryonic, as well as the germ cell lineage itself. The precursor lesion, composed of primordial germ cells/gonocytes, is referred to as carcinoma in situ of the testis (CIS) and gonadoblastoma of the dysgenetic gonad. These pre-malignant cells retain embryonic characteristics, which probably explains the unique responsiveness of the derived tumours to DNA-damaging agents. Development of CIS and gonadoblastoma is crucially dependent on the micro-environment created by Sertoli cells in the testis, and granulosa cells in the dysgenetic gonad. OCT3/4 has high sensitivity and specificity for CIS/gonadoblastoma, seminoma, and embryonal carcinoma, and is useful for the detection of CIS cells in semen, thus a promising tool for non-invasive screening. Overdiagnosis of CIS due to germ cell maturation delay can be avoided using immunohistochemical detection of stem cell factor (SCF). Immunohistochemistry is helpful in making the distinction between seminoma and embryonal carcinoma, especially SOX17 and SOX2. The different non-seminomatous histological elements can be recognized using various markers, such as AFP and hCG, while others need confirmation. The value of micro-satellite instability as well as BRAF mutations in predicting treatment resistance needs validation in prospective trials. The availability of representative cell lines, both for seminoma and for embryonal carcinoma, allows mechanistic studies into the initiation and progression of this disease.
人类生殖细胞肿瘤（GCTs）包括几种具有不同发病机制和临床行为的肿瘤类型。已提出分为五种亚型的分类方法。在此，将对所谓的II型睾丸生殖细胞肿瘤（TGCTs），即精原细胞瘤和非精原细胞瘤进行综述，重点关注发病机制和临床意义。已确定了各种风险因素，这些因素定义了适合早期诊断的男性亚群。TGCTs具有全能性，能够产生所有分化谱系，包括胚胎和胚外谱系以及生殖细胞谱系本身。由原始生殖细胞/生殖母细胞组成的前驱病变被称为睾丸原位癌（CIS）和发育异常性腺中的性腺母细胞瘤。这些癌前细胞保留胚胎特征，这可能解释了衍生肿瘤对DNA损伤剂的独特反应性。CIS和性腺母细胞瘤的发生关键取决于睾丸中支持细胞以及发育异常性腺中颗粒细胞所创造的微环境。OCT3/4对CIS/性腺母细胞瘤、精原细胞瘤和胚胎癌具有高敏感性和特异性，并且可用于检测精液中的CIS细胞，因此是一种有前景的非侵入性筛查工具。使用干细胞因子（SCF）的免疫组织化学检测可避免因生殖细胞成熟延迟导致的CIS过度诊断。免疫组织化学有助于区分精原细胞瘤和胚胎癌，特别是SOX17和SOX2。使用各种标志物，如甲胎蛋白（AFP）和人绒毛膜促性腺激素（hCG），可以识别不同的非精原细胞瘤组织学成分，而其他成分则需要进一步确认。微卫星不稳定性以及BRAF突变在预测治疗耐药性方面的价值需要在前瞻性试验中进行验证。精原细胞瘤和胚胎癌代表性细胞系的可用性使得能够对该疾病的起始和进展进行机制研究。
