NTRK重排/扩增胃癌4例临床病理学特征

Clinicopathological features of gastric carcinomas with NTRK-rearrangement/amplification:report of four cases

目的探讨具有NTRK重排/扩增胃癌的临床病理学特征、免疫表型和分子遗传学特征。方法收集南京大学医学院附属鼓楼医院2011年1月至2020年9月确诊NTRK重排/扩增胃癌病例的临床病理资料,分析其临床病理学特征、免疫表型及分子病理学改变,并复习相关文献。结果共4例具有NTRK重排/扩增的胃癌病例,患者均为男性,年龄57~67岁(平均63岁)。肿瘤最大径范围3.5~5.2 cm(平均4.8 cm)。所有肿瘤均位于胃窦部。4例患者均行胃癌根治术,术后进行随访。形态学方面,所有具有NTRK重排/扩增胃癌都显示出具有肠母细胞分化胃癌的组织学特征,表现为肿瘤细胞呈管状/乳头状排列,可见泡状核,胞质淡染或透明。免疫组织化学方面4例均显示Pan-TRK不同程度的细胞质阳性表达。分子病理方面所有NTRK重排/扩增胃癌均使用NTRK1/2/3分离探针进行荧光原位杂交检测,2例出现NTRK易位,另外2例出现NTRK扩增。2例易位病例通过RNAseq二代测序进一步验证,证实1例NTRK1基因易位(TPM3-NTRK1融合)和1例NTRK2基因易位(NTRK2-SMCHD1融合)。结论NTRK突变在胃癌中发生频率较低,本组病例主要发生在胃窦,形态学具有肠母细胞分化特征。该肿瘤具有独特的组织学特征、免疫表型及分子特征,需要病理医师予以较高关注,以有效指导临床医师对患者进行治疗。

Objective To investigate the clinicopathological,immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification.Methods The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,China,were collected.The clinicopathological,immunophenotypic and molecular pathological features were analyzed.The relevant literature was reviewed.Results There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification.All 4 patients were male,aged 57-67 years(average,63 years).Tumor sizes ranged from 3.5 to 5.2 cm(average,4.8 cm).All tumors were in the antrum.All 4 patients underwent radical gastrectomy and were followed up after the surgery.Morphologically,all tumors showed histological features with enteroblastic-differentiated gastric carcinoma.Tumor cells showed predominantly tubular/papillary architecture,with conspicuous vesicular nuclei and pale staining or transparent cytoplasm.Immunohistochemistry showed pan-TRK expression in all cases,with various degrees of positivity in the cytoplasm.All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization.There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases.These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation(TPM3-NTRK1)and NTRK2 gene translocation(NTRK2-SMCHD1)occurred in two cases,respectively.Conclusions NTRK mutation occurs less frequently in gastric cancer.In this study,the cases mainly occur in the antrum.The morphology has the characteristics of enteroblastic differentiation.The tumors have unique histological,immunophenotypic and molecular characteristics,which require much attention from pathologists to effectively guide clinicians to choose the best treatment.