Institute of Pathology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany.
Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Histopathology. 2019 Sep;75(3):431-436. doi: 10.1111/his.13890. Epub 2019 Jul 19.
In thymic carcinomas, focal clear cell change is a frequent finding. In addition to a prominent, diffuse clear cell morphology, some of these carcinomas show an exuberant hyalinised extracellular matrix, and therefore probably represent a separate entity. However, a characteristic genomic alteration remains elusive. We hypothesised that, analogous to hyalinising clear cell carcinomas of the salivary gland, hyalinising clear cell carcinomas of the thymus might also harbour EWSR1 translocations.
We identified nine archived cases of thymic carcinoma with focal clear cell features and two cases that showed remarkable hyalinised stroma and prominent, diffuse clear cell morphology. These two cases expressed p40 and were negative for Pax8, CD5, and CD117. Programmed death-ligand 1 was highly positive in one case (70%), and negative in the other one. EWSR1 translocation was identified in both cases of hyalinising clear cell carcinoma, and was absent in all nine carcinomas that showed clear cell features without substantial hyalinisation. In one of the EWSR1-translocated cases, a fusion between exon 13 and exon 6 of EWSR1 and ATF1, respectively was identified by next-generation sequencing.
These findings suggest that the EWSR1 translocation and possibly the EWSR1-ATF1 fusion might be unifying genomic alterations for thymic clear cell carcinomas with prominent hyalinised stroma, for which we propose the term 'hyalinising clear cell carcinoma of the thymus'. Because the immunophenotype is unspecific, testing for the EWSR1 translocation might be helpful in discriminating this entity from other thymic neoplasms or metastases, in particular those with clear cell change.
胸腺癌中常可见局灶性透明细胞改变。除了明显弥漫的透明细胞形态外，这些癌中的一些还表现出丰富的玻璃样细胞外基质，因此可能代表一种独立的实体。然而，其特征性的基因组改变仍难以捉摸。我们假设，类似于唾液腺的透明细胞癌，胸腺癌的透明细胞癌也可能存在 EWSR1 易位。
我们鉴定了 9 例具有局灶性透明细胞特征的胸腺癌存档病例和 2 例表现出明显玻璃样化基质和明显弥漫性透明细胞形态的病例。这两个病例均表达 p40，且阴性表达 Pax8、CD5 和 CD117。程序性死亡配体 1 在一个病例中高度阳性（70%），而另一个病例则为阴性。在这两个透明细胞癌中均发现了 EWSR1 易位，而在没有明显玻璃样化的 9 例透明细胞特征的癌中均未发现 EWSR1 易位。在一个 EWSR1 易位的病例中，通过下一代测序分别鉴定出 EWSR1 外显子 13 与外显子 6 和 ATF1 的融合。
这些发现表明，EWSR1 易位和可能的 EWSR1-ATF1 融合可能是具有显著玻璃样化基质的胸腺癌的统一基因组改变，我们建议将其命名为“胸腺癌透明细胞癌”。由于免疫表型不具有特异性，因此检测 EWSR1 易位可能有助于将该实体与其他胸腺瘤或转移瘤区分开来，特别是那些具有透明细胞改变的肿瘤。
