Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation
New disease entities have been emerging based on molecular pathological findings, such as pseudoendocrine sarcoma and mesenchymal neoplasm with GLI1 gene alterations, which resemble well-differentiated neuroendocrine tumors. We report a unique case of a gastric submucosal neoplasm of approximately 1...
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Frontiers Media S.A.
2025-04-01
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| author | Karin Ashizawa Tsuyoshi Saito Tsuyoshi Saito Yukinori Yube Shinji Mine Tetsu Fukunaga Cristina R. Antonescu Takashi Yao |
| author_facet | Karin Ashizawa Tsuyoshi Saito Tsuyoshi Saito Yukinori Yube Shinji Mine Tetsu Fukunaga Cristina R. Antonescu Takashi Yao |
| author_sort | Karin Ashizawa |
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| description | New disease entities have been emerging based on molecular pathological findings, such as pseudoendocrine sarcoma and mesenchymal neoplasm with GLI1 gene alterations, which resemble well-differentiated neuroendocrine tumors. We report a unique case of a gastric submucosal neoplasm of approximately 1.5 cm in size with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation in a 66-year-old man. It was incidentally identified by routine health screening, and was a slowly growing tumor. Macroscopically, it was a slightly protruded tumor into the mucosa, and was primarily located from the submucosa to the muscularis propria. It was a well-defined lesion measured approximately 20 mm, and was almost stable during almost 5 years after initial identification of the tumor. Uniform round-to-epithelioid cells arranged in solid trabeculae with a microtubular/acinar appearance were seen microscopically. Occasional mitotic figures were noted, but no necrosis was observed. Immunohistochemistry (IHC) demonstrated diffuse expression of pan-cytokeratin, CD10, and CD56 without neuroendocrine markers (chromogranin A, synaptophysin, and INSM1). Molecular analysis confirmed the presence of a hot spot CTNNB1 mutation (S33C), supported by diffuse β-catenin nuclear expression by IHC. Further molecular investigations revealed the absence of GLI1 gene rearrangements, GLI1 amplification, and other fusions. Several differential diagnoses were considered; however, none adequately fit the criteria. The patient remained disease-free for 24 months postoperatively without further adjuvant therapy. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-00d839be22bb4384a1ef46b6688f719d2025-08-20T01:55:12ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-04-011210.3389/fmed.2025.15266141526614Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiationKarin Ashizawa0Tsuyoshi Saito1Tsuyoshi Saito2Yukinori Yube3Shinji Mine4Tetsu Fukunaga5Cristina R. Antonescu6Takashi Yao7Department of Human Pathology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, JapanDepartment of Human Pathology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, JapanIntractable Disease Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, JapanDepartment of Upper Gastroenterological Surgery, Juntendo University Hospital, Bunkyo-ku, JapanDepartment of Upper Gastroenterological Surgery, Juntendo University Hospital, Bunkyo-ku, JapanDepartment of Upper Gastroenterological Surgery, Juntendo University Hospital, Bunkyo-ku, JapanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Human Pathology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, JapanNew disease entities have been emerging based on molecular pathological findings, such as pseudoendocrine sarcoma and mesenchymal neoplasm with GLI1 gene alterations, which resemble well-differentiated neuroendocrine tumors. We report a unique case of a gastric submucosal neoplasm of approximately 1.5 cm in size with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation in a 66-year-old man. It was incidentally identified by routine health screening, and was a slowly growing tumor. Macroscopically, it was a slightly protruded tumor into the mucosa, and was primarily located from the submucosa to the muscularis propria. It was a well-defined lesion measured approximately 20 mm, and was almost stable during almost 5 years after initial identification of the tumor. Uniform round-to-epithelioid cells arranged in solid trabeculae with a microtubular/acinar appearance were seen microscopically. Occasional mitotic figures were noted, but no necrosis was observed. Immunohistochemistry (IHC) demonstrated diffuse expression of pan-cytokeratin, CD10, and CD56 without neuroendocrine markers (chromogranin A, synaptophysin, and INSM1). Molecular analysis confirmed the presence of a hot spot CTNNB1 mutation (S33C), supported by diffuse β-catenin nuclear expression by IHC. Further molecular investigations revealed the absence of GLI1 gene rearrangements, GLI1 amplification, and other fusions. Several differential diagnoses were considered; however, none adequately fit the criteria. The patient remained disease-free for 24 months postoperatively without further adjuvant therapy.https://www.frontiersin.org/articles/10.3389/fmed.2025.1526614/fullpseudoendocrine sarcomastomachCTNNB1cytokeratinepithelialneuroendocrine |
| spellingShingle | Karin Ashizawa Tsuyoshi Saito Tsuyoshi Saito Yukinori Yube Shinji Mine Tetsu Fukunaga Cristina R. Antonescu Takashi Yao Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation Frontiers in Medicine pseudoendocrine sarcoma stomach CTNNB1 cytokeratin epithelial neuroendocrine |
| title | Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation |
| title_full | Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation |
| title_fullStr | Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation |
| title_full_unstemmed | Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation |
| title_short | Case Report: Gastric submucosal neoplasm with CTNNB1 mutation showing GLI1 overexpression and epithelial differentiation |
| title_sort | case report gastric submucosal neoplasm with ctnnb1 mutation showing gli1 overexpression and epithelial differentiation |
| topic | pseudoendocrine sarcoma stomach CTNNB1 cytokeratin epithelial neuroendocrine |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1526614/full |
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