Abstract：
Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of The Journal of Pathology. The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen-activated protein kinase pathway mutations or a ploidy shift with secondary TP53 mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS-derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
摘要：
睾丸生殖细胞肿瘤（TGCT）源自未成熟（I型）和多能生殖细胞原位瘤（GCNIS，II型）具有显着的表型异质性和可塑性。相比之下,罕见的精母细胞肿瘤(SpT，类型III),来自成熟的精原细胞，被认为是同质的良性肿瘤，但偶尔可能表现为间变性或侵袭性肉瘤样肿瘤。虽然已经提出了各种致癌过程，在最近一期的《病理学杂志》上描述的一系列非典型SpT的分子表征之前，驱动恶性进展的确切机制仍然难以捉摸。新出现的图片表明SpTs存在两个不同的轨迹，涉及RAS/丝裂原激活的蛋白激酶途径突变或具有次级TP53突变和/或染色体12p获得的倍性移位，后者被称为II型GCNIS衍生的TGCTs的pathognomonic。这里,我们讨论这些发现的含义，从生殖细胞生物学的角度和不同TGCT的独特特征来看。SpTs的进化表型，由基因组和表观遗传变化诱导，说明可塑性的概念适用于所有生殖细胞肿瘤，使它们具有内在的异质性，并能够在进展过程中发生显著的转化。©2024作者由JohnWiley＆SonsLtd代表英国和爱尔兰病理学会出版的病理学杂志。
