Objective: To investigate the clinicopathological, immunophenotypic and molecular genetic characteristics, and differential diagnosis of NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) in the gastrointestinal tract. Methods: Two NTRK-RSCNs diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China and one case diagnosed at Zhengzhou Central Hospital, Zhengzhou, China from 2019 to 2022 were collected. The clinical data, histopathology, immunophenotypes and prognosis were analyzed. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect NTRK gene rearrangements, while relevant literature was also reviewed and discussed. Results: Two patients were male and one was female, with the age of 17, 47 and 62 years, respectively. The tumors were located in the duodenum, ascending colon and descending colon, respectively. The tumors were protuberant masses with gray and rubbery sections. Their maximum diameter was 2.5, 5.0 and 10.0 cm, respectively. Histologically, the tumors invaded mucosa, intrinsic muscle and serosal adipose tissue. Tumor cells consisted of spindle or oval shaped cells with monotonous morphology and arranged in bundles or stripes pattern. Spindle cells were mildly to moderately atypical, with slightly eosinophilic cytoplasm and inconspicuous nucleoli. Necrosis and mitotic figures were observed in one high-grade tumor. All tumors expressed CD34, S-100 and pan-TRK in varying degrees. FISH analysis showed that NTRK1 gene was break-apart in 1 case and NTRK2 gene break-apart in 2 cases. NGS technologies showed LMNA::NTRK1 fusion in one case, STRN::NTRK2 fusion in another case. All patients recovered well after the surgery without recurrence at the end of the follow-up. Conclusions: NTRK-RSCN is rarely diagnosed in the gastrointestinal tract and has significant variations in morphology. It overlaps with various other mesenchymal tumors which should be considered as differential diagnoses. Be familiar with the features of histological morphology in combination with immunophenotype and molecular genetic characteristics can not only help diagnose NTRK-RSCNs, but provide therapeutic targets for clinical treatment.
目的： 探讨胃肠道原发的具有NTRK重排的梭形细胞肿瘤（NTRK-rearranged spindle cell neoplasms，NTRK-RSCN）临床病理学特征、免疫表型、分子病理特点、鉴别诊断以及临床预后。 方法： 收集2019—2022年郑州大学第一附属医院病理科2例及郑州市中心医院1例NTRK-RSCN病理标本，分析其临床资料、组织病理学特点、免疫组织化学染色特征及预后，应用荧光原位杂交法（FISH）及二代测序检测NTRK基因重排情况，复习相关文献并进行探讨。 结果： 患者中2例男性，1例女性，年龄分别为17、47、62岁；3例肿瘤分别位于十二指肠、升结肠及降结肠。大体上，肿瘤最大径分别为2.5、5.0、10.0 cm，均为隆起型肿物，切面灰白、质韧，其中1例可见坏死。镜下观察：肿瘤主要位于黏膜下及固有肌层间，由形态较一致的梭形/卵圆形细胞组成，呈条束状或席纹状排列，1例肿瘤细胞间穿插脂肪细胞及胶原纤维；梭形细胞呈轻到中度异型，胞质稍嗜酸，核仁不明显，1例高级别肿瘤可见坏死及核分裂象。3例肿瘤细胞均不同程度表达CD34、S-100及pan-TRK蛋白。FISH检测结果显示3例均具有NTRK基因断裂，其中2例NTRK2基因发生断裂，1例NTRK1基因发生断裂。患者术后均恢复良好，尚无复发。二代测序检测了2例，其中1例出现LMNA：：NTRK1基因融合，另1例出现STRN：：NTRK2基因融合。 结论： 发生在胃肠道的NTRK-RSCN在组织形态学上变异较大，且与多种软组织肿瘤存在形态学重合，诊断时要注意鉴别；熟悉其组织形态学特征，并结合相应的免疫组织化学和分子病理检测，可避免误诊，并为临床提供治疗靶点。.