Pathology Unit, Arcispedale Santa Maria Nuova, Azienda USL-IRCCS, Reggio Emilia, Italy.
Laboratory of Translational Research, Arcispedale Santa Maria Nuova, Azienda USL-IRCCS, Reggio Emilia, Italy.
Mod Pathol. 2019 Jun;32(6):787-798. doi: 10.1038/s41379-018-0199-z. Epub 2019 Feb 5.
Angiosarcoma and anaplastic carcinoma are the most lethal neoplasms of the thyroid worldwide and share some similarities, which have led to a longstanding controversy on their etiopathological relationship. Thyroid angiosarcomas are characterized by vessel formation and an immunophenotype common to endothelial cells, while anaplastic carcinomas are partially or wholly composed of mesenchymal-like cells that have lost the morphologic and functional features of normal thyroid follicular cells. To investigate whether angiosarcomas represent the endothelial extreme of the differentiation spectrum of carcinomas or they are bona fide vascular neoplasms, we studied the clinico-morphologic and genetic characteristics of a series of 10 angiosarcomas and 22 anaplastic carcinomas. Immunohistochemically, among the endothelial markers, CD31 and ERG were the most consistently expressed in angiosarcomas. Among the markers of thyroid origin, PAX8 was the most reliable in anaplastic carcinomas, while TTF-1 reactivity was found in only 5% of anaplastic carcinomas and thyroglobulin was always negative. Pankeratin reacted with most angiosarcomas and anaplastic carcinomas and is therefore not useful in the differential diagnosis. Interestingly a mutated pattern of p53 immunostaining prompted a diagnosis of anaplastic carcinoma. To compare the genetic profile, we used the NGS approach to sequence hotspot regions within a panel of 57 genes. As a result, only a few mutations were found in angiosarcomas and all of them were single events (no TP53 or TERT mutation). On the other hand, anaplastic carcinomas were characterized by a higher number of mutations, and TP53 and TERT promoter mutations were the most frequent genetic alterations. The lack in angiosarcomas of the common mutations identified in anaplastic carcinomas supports a different genetic origin and strongly suggests that, in spite of a shared sarcomatous morphology and a similar clinical aggressiveness, angiosarcomas and anaplastic carcinomas rely on a completely different set of genetic alterations during their evolution.
血管肉瘤和间变性癌是全球甲状腺最致命的肿瘤，它们具有一些相似之处，这导致了它们在病因病理学关系上的长期争议。甲状腺血管肉瘤的特征是血管形成和内皮细胞共有的免疫表型，而间变性癌部分或完全由失去正常甲状腺滤泡细胞形态和功能特征的间充质样细胞组成。为了研究血管肉瘤是否代表癌的分化谱的内皮极端，或者它们是否是真正的血管肿瘤，我们研究了一系列 10 例血管肉瘤和 22 例间变性癌的临床形态学和遗传特征。免疫组化染色显示，在内皮标志物中，CD31 和 ERG 在血管肉瘤中表达最一致。在甲状腺来源的标志物中，PAX8 在间变性癌中最可靠，而 TTF-1 反应性仅在 5%的间变性癌中发现，甲状腺球蛋白始终为阴性。大多数血管肉瘤和间变性癌都对 Pankeratin 有反应，因此在鉴别诊断中没有用。有趣的是，p53 免疫染色的突变模式提示诊断为间变性癌。为了比较遗传谱，我们使用 NGS 方法对 57 个基因的热点区域进行测序。结果发现，血管肉瘤中只有少数突变，而且都是单事件（无 TP53 或 TERT 突变）。另一方面，间变性癌的突变数量较多，TP53 和 TERT 启动子突变是最常见的遗传改变。血管肉瘤缺乏间变性癌中常见的突变，支持不同的遗传起源，并强烈表明，尽管具有相似的肉瘤形态和相似的临床侵袭性，血管肉瘤和间变性癌在其进化过程中依赖于完全不同的遗传改变。
