Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommon histopathological and clinical features. Here we report seven SMARCB1-deficient intracranial tumors sharing distinct clinical, histopathological and molecular features. Median age of the four females and three males was 40 years (range 15-61 years). All tumors were located in the pineal region. Histopathologically, these tumors displayed spindled and epithelioid cells embedded in a desmoplastic stroma alternating with a variable extent of a loose myxoid matrix. All cases showed loss of nuclear SMARCB1/INI1 protein expression, expression of EMA and CD34 was frequent and the Ki67/MIB1 proliferation index was low in the majority of cases (median 3%). Three cases displayed heterozygous SMARCB1 deletions and two cases a homozygous SMARCB1 deletion. On sequencing, one tumor showed a 2 bp deletion in exon 4 (c.369_370del) and one a short duplication in exon 3 (c.237_276dup) both resulting in frameshift mutations. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-SNE analysis and hierarchical clustering analysis, however, all tumors grouped closely together and showed similarities with ATRT-MYC. After a median observation period of 48 months, three patients were alive with stable disease, whereas one patient experienced tumor progression and three patients had succumbed to disease. In conclusion, our series represents an entity with distinct clinical, histopathological and molecular features showing epigenetic similarities with ATRT-MYC. We propose the designation desmoplastic myxoid tumor (DMT), SMARCB1-mutant, for these tumors.

中文翻译：

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SMARCB1 突变型促纤维增生性粘液样肿瘤：青少年和成人松果体区肿瘤的临床、组织病理学和分子特征。

非典型畸胎瘤/横纹肌样瘤（ATRT）是一种高度恶性的脑肿瘤，主要发生在婴儿中。SMARCB1 基因突变是特征性遗传病变。青少年和成人中的 SMARCB1 突变肿瘤很罕见，可能表现出不常见的组织病理学和临床特征。在这里，我们报告了七种 SMARCB1 缺陷的颅内肿瘤，它们具有不同的临床、组织病理学和分子特征。四名女性和三名男性的中位年龄为 40 岁（范围为 15-61 岁）。所有肿瘤均位于松果体区。在组织病理学上，这些肿瘤显示出嵌入促纤维增生基质中的梭形细胞和上皮样细胞，与不同程度的松散粘液样基质交替。所有病例均显示核SMARCB1/INI1蛋白表达缺失，EMA和CD34表达频繁，大多数病例Ki67/MIB1增殖指数较低（中位3%）。3 例显示杂合 SMARCB1 缺失，2 例显示纯合 SMARCB1 缺失。测序结果显示，一种肿瘤在外显子 4 (c.369_370del) 中显示 2 bp 缺失，另一种肿瘤在外显子 3 (c.237_276dup) 中显示短重复，均导致移码突变。大多数 DNA 甲基化谱无法使用海德堡脑肿瘤分类器（版本 v11b4）进行分类。然而，通过无监督的 t-SNE 分析和层次聚类分析，所有肿瘤都紧密分组在一起，并显示出与 ATRT-MYC 的相似性。中位观察期为 48 个月后，三名患者病情稳定，仍存活，而一名患者出现肿瘤进展，三名患者因疾病死亡。总之，我们的系列代表了一个具有独特临床、组织病理学和分子特征的实体，显示出与 ATRT-MYC 的表观遗传相似性。我们建议将这些肿瘤命名为促纤维增生性粘液样肿瘤 (DMT)、SMARCB1 突变体。