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.

中文翻译：

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对非典型精细胞肿瘤的新分析揭示了生殖细胞肿瘤的广泛异质性和可塑性†

源自未成熟生殖细胞原位肿瘤（I 型）和多能生殖细胞原位肿瘤（ GCNIS，II 型）的睾丸生殖细胞肿瘤（TGCT）具有显着的表型异质性和可塑性。相比之下，罕见的精细胞肿瘤（SpT，III 型）源自成熟的精原细胞，被认为是同质良性肿瘤，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，但驱动恶性进展的精确机制仍然难以捉摸，直到最近一期《病理学杂志》描述了一系列非典型 SpT 的分子特征。新出现的图片表明，SpT 存在两种不同的轨迹，涉及 RAS/丝裂原激活蛋白激酶途径突变或伴随二次TP53突变的倍性转变和/或染色体 12p 的获得，后者被称为 II 型 GCNIS 的特有特征。派生的 TGCT。在这里，我们从生殖细胞生物学的角度和不同 TGCT 的独特特征讨论这些发现的含义。由基因组和表观遗传变化诱导的 SpT 不断演变的表型表明，可塑性的概念适用于所有生殖细胞肿瘤，使它们具有固有的异质性，并且能够在进展过程中发生显着的转化。 © 2024 作者。《病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。