Head and Neck Mesenchymal Neoplasms With GLI1 Gene Alterations A Pathologic Entity With Distinct Histologic Features and Potential for Distant Metastasis
Head and Neck Mesenchymal Neoplasms With GLI1 Gene Alterations A Pathologic Entity With Distinct Histologic Features and Potential for Distant Metastasis
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DOI：
10.1097/pas.0000000000001439
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Antonescu, Cristina R.
中科院分区：
文献类型：
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作者：
Xu, Bin;Chang, Koping;Antonescu, Cristina R.
具有 GLI1 基因融合或扩增的软组织肿瘤最近被描述为一种独特的病理实体，具有确定的恶性肿瘤风险。我们在此通过调查一组 11 个具有 GLI1 改变的头颈部病变（其中 8 个来自舌头）的临床病理学和分子特征来扩展这些发现。肿瘤常见于 30 多岁的男性（男女比例为 2.7:1；范围：1 至 65）。肿瘤表现出多结节生长模式、由精致的树枝状血管网络分隔的嵌套结构、单调的圆形至卵圆形核和透明的细胞质。肿瘤突出到血管间隙是常见的。通过荧光原位杂交和/或靶向 RNA 测序研究遗传改变。七个肿瘤含有 GLI1 与以下伙伴的融合：ACTB (n=4)、PTCH1 (n=2) 或 MALAT1 (n=1)。其余 4 例显示 GLI1 与 CDK4 和 MDM2 基因共扩增。肿瘤通常呈 S100 蛋白和 CD56 阳性。 CDK4、MDM2 和 STAT6 在 GLI1 扩增的肿瘤中呈阳性。 6 名进行随访的患者中，有 2 名（GLI1 扩增和 PTCH1-GLI1 融合各 1 名）出现远处转移。两种肿瘤均显示出高有丝分裂指数和肿瘤坏死。头颈部区域，特别是舌头，是 GLI1 相关间质肿瘤的常见部位。尽管与之前报道的“t(7,12)易位周细胞瘤”存在形态学重叠（通常发生在舌头中），但我们的研究结果扩展了最初的发现，包括更可变的免疫表型、晚期远处转移的倾向以及 GLI1 致癌激活的替代机制，例如各种 GLI1 融合伙伴或 GLI1 与 MDM2 和 CDK4 基因的共扩增。
Soft tissue tumors with GLI1 gene fusions or amplifications have been recently described as a unique pathologic entity with an established risk of malignancy. We herein expand these findings by investigating a cohort of 11 head and neck lesions with GLI1 alterations, including 8 from the tongue, for their clinicopathologic and molecular features. The tumors commonly affected males in their 30s (male:female ratio 2.7:1; range: 1 to 65). Tumors showed a multinodular growth pattern, nested architecture separated by a delicate, arborizing vascular network, monotonous round to ovoid nuclei, and clear cytoplasm. Tumor protrusion into vascular spaces was common. Genetic alterations were investigated by fluorescence in situ hybridization and/or targeted RNA sequencing. Seven tumors harbored GLI1 fusions with the following partners: ACTB (n=4), PTCH1 (n=2), or MALAT1 (n=1). The remaining 4 cases showed coamplifications of GLI1 with CDK4 and MDM2 genes. Tumors were commonly positive for S100 protein and CD56. CDK4, MDM2, and STAT6 were positive in GLI1-amplified tumors. Two of 6 patients with available follow-up (1 each with GLI1 amplification and PTCH1-GLI1 fusion) developed distant metastases. Both tumors showed a high mitotic index and tumor necrosis. The head and neck region, particularly tongue, is a common location for GLI1-related mesenchymal tumors. Although a morphologic overlap was noted with the previously reported "pericytoma with t(7,12) translocation," often occurring in the tongue, our findings expand the original findings, to include a more variable immunophenotype, propensity for late distant metastases, and alternative mechanisms of GLI1 oncogenic activation, such as various GLI1 fusion partners or GLI1 coamplifications with MDM2 and CDK4 genes.