GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions. We studied three unique mesenchymal small bowel tumors. Paraffin embedded tumor tissues from these cases and 62 additional tumor samples that included a plexiform fibromyxoma were sequenced using a targeted RNAseq method to detect fusion events. The study patients included two women and one man who were 52, 80, and 22 years of age at the time of diagnosis. The tumors involved the submucosa and muscularis propria of the duodenum, jejunum, and ileum. All 3 tumors contained a proliferation of monotonous oval or spindle cells with scattered, somewhat dilated vessels. Two cases showed epithelioid structures such as glands, tubules, or nests. Immunohistochemical analysis revealed cytokeratin expression in the epithelioid components of both tumors displaying these features, and variable numbers of mesenchymal cells. Diffuse CD56 positivity was seen in the mesenchymal component of 2 tumors and desmin and smooth muscle actin staining in the other tumor. Immunostains for S-100 protein, DOG-1, and CD117 were negative in all cases. GLI1 fusions with different partner genes were detected in all tumors, and in the plexiform fibromyxoma, used as a control. Validation by fluorescence in situ hybridization was performed. None of the tumors have recurred or metastasize after surgery. We describe novel GLI1 fusions in 3 mesenchymal neoplasms of the small intestine, including 2 with biphenotypic features. Thus far, all cases have pursued indolent clinical courses. We propose the term “GLI1-rearranged enteric tumor” to encompass this group of unique neoplasms of the small intestine that harbor GLI1 gene fusions and expand the spectrum of gastrointestinal neoplasms with these alterations.

GLI1编码一种转录因子，靶向影响干细胞增殖的细胞周期调节因子。GLI1基因融合最初在具有 at[7;12] 易位的周细胞瘤中被描述，最近在胃丛状纤维粘液瘤和胃母细胞瘤中被描述。本研究描述了三种携带GLI1的肠道肿瘤的临床病理学、免疫组织化学和分子特征基因融合。我们研究了三种独特的间充质小肠肿瘤。使用靶向 RNAseq 方法对来自这些病例的石蜡包埋肿瘤组织和 62 个包括丛状纤维粘液瘤的其他肿瘤样本进行测序，以检测融合事件。研究患者包括两名女性和一名男性，诊断时年龄分别为 52 岁、80 岁和 22 岁。肿瘤累及十二指肠、空肠和回肠的粘膜下层和固有肌层。所有 3 个肿瘤均含有单调的椭圆形或梭形细胞增生，伴有散在的、略微扩张的血管。两例显示上皮样结构，如腺体、小管或巢。免疫组织化学分析显示，两种肿瘤的上皮样成分中的细胞角蛋白表达都显示出这些特征，并且间充质细胞数量不定。在 2 个肿瘤的间充质成分中观察到弥漫性 CD56 阳性，在另一个肿瘤中观察到结蛋白和平滑肌肌动蛋白染色。S-100 蛋白、DOG-1 和 CD117 的免疫染色在所有病例中均为阴性。在所有肿瘤中检测到GLI1与不同伙伴基因的融合，并在用作对照的丛状纤维粘液瘤中检测到。通过荧光原位杂交进行验证。手术后没有肿瘤复发或转移。我们描述了3 种小肠间充质肿瘤中的新型GLI1融合，其中 2 种具有双表型特征。到目前为止，所有病例都进行了惰性临床课程。我们建议使用术语“ GLI1重排肠道肿瘤”来涵盖这组具有GLI1基因融合的独特小肠肿瘤，并通过这些改变扩大胃肠道肿瘤的范围。