Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor that may not only contain rhabdoid tumor cells but also poorly differentiated small-round-blue cells as well as areas with mesenchymal or epithelial differentiation. Little is known on factors associated with histopathological diversity. Recent studies demonstrated three molecular subgroups of AT/RT, namely ATRT-TYR, ATRT-SHH, and ATRT-MYC. We thus aimed to investigate if morphological patterns might be related to molecular subgroup status. Hematoxylin-eosin stained sections of 114 AT/RT with known molecular subgroup status were digitalized and independently categorized by nine blinded observers into four morphological categories, that is, “rhabdoid,” “small-round-blue,” “epithelial,” and “mesenchymal.” The series comprised 48 ATRT-SHH, 40 ATRT-TYR, and 26 ATRT-MYC tumors. Inter-observer agreement was moderate but significant (Fleiss’ kappa = 0.47; 95% C.I. 0.41-0.53; p < 0.001) and there was a highly significant overall association between morphological categories and molecular subgroups for each of the nine observers (p < 0.0001). Specifically, the category “epithelial” was found to be over-represented in ATRT-TYR (p < 0.000001) and the category “small-round-blue” to be over-represented in ATRT-SHH (p < 0.01). The majority of ATRT-MYC was categorized as “mesenchymal” or “rhabdoid,” but this association was less compelling. The specificity of the category “epithelial” for ATRT-TYR was highest and accounted for 97% (range: 88-99%) whereas sensitivity was low [49% (range: 35%–63%)]. In line with these findings, cytokeratin-positivity was highly overrepresented in ATRT-TYR. In conclusion, morphological features of AT/RT might reflect molecular alterations and may also provide a first hint on molecular subgroup status, which will need to be confirmed by DNA methylation profiling.

中文翻译：

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非典型畸胎样/横纹肌样肿瘤的组织病理学模式与分子亚群有关

非典型畸胎样/横纹肌样肿瘤（AT/RT）是一种高度恶性的肿瘤，不仅可能含有横纹肌样肿瘤细胞，而且可能含有分化差的小圆形蓝色细胞以及具有间充质或上皮分化的区域。与组织病理学多样性相关的因素知之甚少。最近的研究证明了 AT/RT 的三个分子亚群，即 ATRT-TYR、ATRT-SHH 和 ATRT-MYC。因此，我们旨在调查形态模式是否可能与分子亚群状态有关。将 114 个具有已知分子亚组状态的 AT/RT 的苏木精-伊红染色切片数字化，并由九名盲法观察者独立分类为四个形态类别，即“横纹肌”、“小圆形蓝色”、“上皮”和“间充质。” 该系列包括 48 个 ATRT-SHH、40 个 ATRT-TYR 和 26 个 ATRT-MYC 肿瘤。p  < 0.001），并且对于九名观察者中的每一位，形态学类别和分子亚群之间存在高度显着的整体关联（p  < 0.0001）。具体而言，发现“上皮”类别在 ATRT-TYR 中的比例过高（p  < 0.000001），而“小圆形蓝色”类别在 ATRT-SHH 中的比例过高（p < 0.01)。大多数 ATRT-MYC 被归类为“间充质”或“横纹肌”，但这种关联不那么引人注目。ATRT-TYR 的“上皮”类别的特异性最高，占 97%（范围：88-99%），而敏感性较低 [49%（范围：35%–63%）]。与这些发现一致，细胞角蛋白阳性在 ATRT-TYR 中的比例过高。总之，AT/RT 的形态学特征可能反映分子变化，也可能提供分子亚群状态的第一个提示，这需要通过 DNA 甲基化分析来证实。