[Mesenchymal tumors with GLI1 gene alterations: a clinicopathological analysis of five cases].

内容摘要

Objective: To investigate the clinicopathological and genetic characteristics of mesenchymal tumors with GLI1 gene alterations. Methods: Five cases diagnosed at the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from 2021 to 2025 were collected. HE and immunohistochemical slides were reviewed. Tumor-associated genetic alterations were detected using a next generation sequencing (NGS) panel of pan-solid tumor genes (468 genes, 116 DNA+352 RNA). Fluorescence in situ hybridization (FISH) was performed to detect GLI1 gene translocation and amplification. Clinical and follow-up data were analyzed. Results: There were 3 females and 2 males, aged 48, 16, 47, 47 and 37 years, respectively. The tumor locations were the tongue, small intestine, ovary, and buttock. Histologically, tumor cells arranged in nest and lobular arrangements; within a partially myxoid stroma with necrosis and calcification, surrounded by a rich fibrovascular network around and a pseudocapsule in some cases. The tumor cells were predominantly round to oval, with fewer short spindled forms, showing mild to moderate atypia and distinct nucleoli. Immunohistochemically, tumor cells variably expressed CD56, S-100, and smooth muscle actin, but were negative for broad-spectrum epithelial markers. GLI1 immunohistochemistry showed diffuse, strong positivity (2 cases stained). Ki-67 proliferation index ranged from 1% to 30%. NGS identified PTCH1::GLI1 fusions in three cases and GLI1 amplification in two. All patients underwent complete surgical resection without adjuvant therapy. During the follow-up (4-16 months), one case recurred, while four remained disease-free. Conclusions: Mesenchymal neoplasm with GLI1 gene alterations is a type of tumor with low malignant potential, representing the biological behavior of low-grade sarcoma. However, it is currently not recognized by the World Health Organization classification. Surgical resection is the preferred treatment. While immunophenotyping lacks specificity, and GLI1 immunohistochemistry could aid in its diagnosis. Definitive diagnosis and differential diagnosis of this tumor require characteristic morphological features combined with molecular confirmation of GLI1 gene fusion or amplification. 目的： 探讨GLI1基因改变的间叶性肿瘤临床病理及遗传学特征。 方法： 回顾性收集华中科技大学同济医学院附属同济医院2021—2025年确诊的5例病例，复核HE及免疫组织化学染色切片，采用泛实体瘤468基因（116 DNA+352 RNA）检测试剂盒进行二代测序检测肿瘤相关基因变异，荧光原位杂交检测GLI1基因易位和扩增并收集临床资料及随访信息。 结果： 5例患者中女性3例，男性2例，年龄分别为48、16、47、47、37岁；肿瘤位于舌、小肠、卵巢及臀部。镜下观察，肿瘤细胞呈巢状、叶状分布，间质部分黏液变性、坏死及钙化，周围可见丰富纤维血管网，部分有假包膜；细胞以圆形、卵圆形为主，少数短梭形，轻至中度异型，核仁明显。免疫组织化学染色，肿瘤细胞不同程度表达CD56、S-100蛋白、平滑肌肌动蛋白，不表达广谱上皮标志物；GLI1弥漫强阳性（2例染色）；Ki-67阳性指数1%~30%。二代测序检测，3例检出PTCH1：：GLI1融合；2例检出GLI1拷贝数扩增。5例患者行肿瘤完整切除，术后未行放化疗。随访4~16个月，1例复发，4例无瘤生存。 结论： GLI1基因改变的间叶性肿瘤是一种具有潜在恶性潜能的肿瘤，为低级别肉瘤的生物学行为，目前WHO肿瘤分类无编码。手术切除为首选治疗。免疫表型缺乏特异性，GLI1免疫组织化学有助于诊断。确诊需结合特征性形态学表现，并依赖分子检测证实GLI1基因融合或扩增。.