Xiang Wentao, Yuan Wei, Ren Lei, Huang Wen, Liang Huaiyu, Huang Jie, Luan Lijuan, Xu Chen, Hou Yingyong
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Diagn Pathol. 2025 Mar 25;20(1):31. doi: 10.1186/s13000-025-01630-5.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The most common mutations in GISTs are those in receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor alpha (PDGFRA). GISTs without KIT or PDGFRA mutations are defined as wild-type (WT) GISTs. The molecular changes, prognosis, and treatments of WT GISTs remain uncertain. Among WT GISTs, neurotrophic tyrosine receptor kinase (NTRK) fusions have rarely been reported. We report a case of quadruple wild-type GIST harboring a novel CDC42BPB::NTRK3 fusion. In this study, we described a 66-year-old male patient with intrajejunal lesion. This case showed massive lymphocytic and plasma cell infiltration, which caused diagnostic difficulties in morphology. CDC42BPB::NTRK3 fusion was detected via next-generation sequencing (NGS), and this finding was confirmed by fluorescence in situ hybridization (FISH), which revealed NTRK3 breakage. However, the expression of the Trk protein in tumor tissue was not detected by immunohistochemistry (IHC). This finding expands the genetic spectrum of NTRK rearrangements in GISTs.
胃肠道间质瘤（GISTs）是胃肠道最常见的间叶组织肿瘤。GISTs最常见的突变是受体酪氨酸激酶（KIT）和血小板衍生生长因子受体α（PDGFRA）的突变。无KIT或PDGFRA突变的GISTs被定义为野生型（WT）GISTs。WT GISTs的分子变化、预后及治疗仍不明确。在WT GISTs中，神经营养性酪氨酸受体激酶（NTRK）融合很少被报道。我们报告1例携带新型CDC42BPB::NTRK3融合的四重野生型GIST病例。在本研究中，我们描述了1例66岁空肠内病变男性患者。该病例显示大量淋巴细胞和浆细胞浸润，在形态学上造成诊断困难。通过二代测序（NGS）检测到CDC42BPB::NTRK3融合，荧光原位杂交（FISH）证实了这一发现，显示NTRK3断裂。然而，免疫组化（IHC）未检测到肿瘤组织中Trk蛋白的表达。这一发现扩展了GISTs中NTRK重排的基因谱。
