Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Thomas M Ulbright

摘要

Gonadal germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain neoplasms. The most dramatic examples of the latter are the frequency of dermoid cyst in the ovary compared to the testis and the reverse pertaining to embryonal carcinoma. Within the teratoma group, there is strong evidence that ovarian and prepubertal testicular teratomas are derived from benign germ cells, a pathogenesis that likely applies also to the rare dermoid cysts and uncommon epidermoid cysts of the testis. In contrast, postpubertal testicular teratomas derive from malignant germ cells, specifically representing differentiation within a preexistent nonteratomatous cancer. As expected, given the foregoing, teratomas in boys are clinically benign, whereas in postpubertal males they are malignant, independent of their degree of immaturity. On the other hand, immaturity is an important finding in ovarian teratomas, irrespective of age, although its significance in children has recently been challenged. It is usually recognized on the basis of embryonic-appearing neuroepithelium, which shows mitotic activity and apoptosis in contrast to differentiated neuroepithelial tissues, which may occur in mature ovarian teratomas. Rarely it is based on the presence of cellular, mitotically active glial tissue. Fetal-type tissues alone are not sufficient for a diagnosis of immature teratoma. Further differences between the teratomatous tumors in the two gonads are the relative frequency of monodermal teratomas in the ovary in contrast to the testis, where only one subset, carcinoids, is seen with any frequency. When uncommon somatic-type malignancies (usually squamous cell carcinoma) occur in mature cystic teratomas of the ovary, this is a de novo form of malignant transformation; similar tumors in the testis, a very rare event, represent overgrowth of teratomatous elements that originated from malignant, nonteratomatous germ cell tumors and, therefore, had previously undergone malignant transformation. Germinomas may have several unusual features in each gonad; these include microcystic arrangements that suggest yolk sac tumor, tubular patterns that mimic Sertoli cell tumor, apparent increased cytological atypia that causes concern for embryonal carcinoma, and prominent syncytiotrophoblast giant cells that suggest choriocarcinoma. Awareness of these variants, good technical preparations, the retained typical cytological features of germinoma cells, and the judicious use of tailored panels of immunohistochemical stains resolve these dilemmas in virtually all instances. Two aspects of germinomas are unique to the testis. Firstly, intertubular growth of small seminomas may cause them to be overlooked. Secondly, the distinctive spermatocytic seminoma occurs only in the testis. A newly recognized aspect of this tumor is the propensity for some to be relatively monomorphic, making them apt to be mistaken for usual seminoma or embryonal carcinoma, although the characteristic polymorphic appearance in some foci, absence of intratubular germ cell neoplasia, unclassified type, and immunohistochemical stains should prevent this error. Cytoplasmic membrane immunoreactivity for placental alkaline phosphatase and CD117, with usual negativity for AE1/AE3 cytokeratins, is helpful in the diagnosis of germinoma. The recently described marker, OCT3/4, a nuclear transcription factor, is especially helpful in the differential of germinoma and embryonal carcinoma with other neoplasms. Yolk sac tumor continues to be confused occasionally with clear cell carcinoma of the ovary. Glandular ('endometrioid-like') yolk sac tumors mimic endometrioid carcinomas; predominant or pure hepatoid yolk sac tumors cause concern

机译：性腺生殖细胞肿瘤仍然是病理学家面临的各种挑战性诊断问题，其正确解决方案通常具有重要的治疗和预后意义。它们在学术上很有趣，因为在两个性腺中表现出生物多样性，并且某些肿瘤的频率发生变化。后者的最典型例子是与睾丸相比，卵巢中皮样囊肿的发生频率，而与胚胎癌有关的情况则相反。在畸胎瘤组中，有强有力的证据表明卵巢和青春期前的睾丸畸胎瘤均来自良性生殖细胞，这种发病机制也可能适用于睾丸的罕见皮样囊肿和罕见的表皮样囊肿。相比之下，青春期后的睾丸畸胎瘤来源于恶性生殖细胞，特别代表先前存在的非畸胎瘤癌中的分化。不出所料，鉴于上述情况，男孩的畸胎瘤在临床上是良性的，而青春期后的男性则是恶性的，与他们的不成熟程度无关。另一方面，不成熟是卵巢畸胎瘤的重要发现，不论年龄大小，尽管最近它在儿童中的重要性受到了挑战。通常基于出现胚胎的神经上皮来识别它，与成熟的卵巢畸胎瘤中可能发生的分化的神经上皮组织相比，它显示出有丝分裂活性和凋亡。很少基于细胞有丝分裂活跃的神经胶质组织的存在。仅胎儿型组织不足以诊断未成熟畸胎瘤。在两个性腺中的畸胎瘤之间的进一步差异是，与睾丸相比，卵巢中的单皮畸胎瘤相对频率较高，而睾丸中的任一频率仅见一个类癌。当在卵巢成熟的囊性畸胎瘤中发生罕见的体细胞型恶性肿瘤（通常为鳞状细胞癌）时，这是从头开始的恶性转化形式。睾丸中的类似肿瘤非常少见，代表源于恶性，非畸胎性生殖细胞肿瘤的畸胎瘤成分过度生长，因此以前曾经历过恶变。生殖器瘤在每个性腺中可能有几个不同寻常的特征。这些包括暗示卵黄囊肿瘤的微囊排列，模仿支持细胞肿瘤的管状模式，引起对胚胎癌的关注的明显细胞异型性增加以及表明绒毛膜绒毛膜癌的突出的合体滋养层巨细胞。意识到这些变体，做好技术准备，保留生殖细胞瘤细胞的典型细胞学特征以及明智地使用量身定制的免疫组化染色剂可以解决几乎所有情况下的这些难题。生瘤的两个方面是睾丸独有的。首先，小的精原细胞瘤的肾小管间生长可能导致它们被忽略。其次，独特的精细胞精原细胞瘤仅发生在睾丸中。这种肿瘤的一个新近认识到的趋势是某些肿瘤具有相对单态性的倾向，使其易于被误认为是普通的精原细胞瘤或胚胎癌，尽管某些病灶的特征性多态性外观，不存在管内生殖细胞瘤形成，未分类的类型以及免疫组化染色应防止此错误。胎盘碱性磷酸酶和CD117的细胞质膜免疫反应性，与AE1 / AE3细胞角蛋白通常呈阴性反应，有助于诊断生殖细胞瘤。最近描述的标志物OCT3 / 4是一种核转录因子，在分化生殖细胞瘤和胚胎癌以及其他肿瘤方面特别有用。卵黄囊肿瘤有时仍与卵巢透明细胞癌混淆。腺样（类子宫内膜样）卵黄囊肿瘤模仿子宫内膜样癌;占优势的或纯净的类肝卵黄囊肿瘤引起关注

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

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