Miyabe Ken, Saito Motonobu, Koyama Kei, Umakoshi Michinobu, Ito Yukinobu, Yoshida Makoto, Kudo-Asabe Yukitsugu, Saito Katsuharu, Nanjo Hiroshi, Maeda Daichi, Matsusaka Keisuke, Goto Akiteru, Kono Koji
Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
BMC Gastroenterol. 2021 Mar 2;21(1):97. doi: 10.1186/s12876-021-01683-y.
Epstein-Barr virus (EBV)-positive gastric carcinoma (GC) is defined by the proliferation of GC cells with EBV infection. The co-existence of EBV-positive and -negative components in a single GC is rare. We report a case of GC with the co-existence of EBV-positive and EBV-negative components, in which we performed-for the first time-various molecular analyses to elucidate their histogenesis.
An 81-year-old man was diagnosed with GC based on the results of endoscopy and a pathological examination of the biopsy specimen. Systemic chemotherapy was performed, since lymph node and lung metastases were diagnosed based on computed tomography. Total gastrectomy and lymph node dissection were performed after chemotherapy, after confirming that the size of the metastatic lymph nodes had decreased and that the lung metastasis had disappeared. Grossly, a type 3 tumor was located in the middle posterior part of the stomach body. At the cut section, the tumor consisted of a white and solid part on the anal side of the tumor and a flat and elevated part on the oral side. Histologically, the former part consisted of GC with lymphoid stroma and the latter part was composed of poorly differentiated adenocarcinoma without prominent lymphocytic infiltration. The two histopathological components were clearly separated from each other. On EBV-encoded small RNA (EBER)-in situ hybridization (ISH), the part with the lymphoid stroma component was positive, while the other part was negative. Immunohistochemistry revealed that both components showed the overexpression of p53. Sequencing of TP53 using DNA extracted from the two components was conducted, and revealed different patterns. Targeted next generation sequencing revealed MYC amplification in the EBV-positive component of the tumor and HER2 amplification in the EBV-negative part. Immunohistochemistry revealed that the EBV-positive part was C-MYC( +)/HER2(-) and the EBV-negative part was C-MYC(-)/HER2( +). Correspondingly, chromogenic ISH and dual-color ISH showed amplification of C-MYC and no amplification of HER2 in the EBV-positive part, and no amplification of C-MYC and amplification of HER2 in the EBV-negative part.
We presented a case of collision of two different GCs composed of EBER-ISH ( +)/C-MYC ( +) and EBER-ISH (-)/HER2 ( +) cells.
爱泼斯坦-巴尔病毒（EBV）阳性胃癌（GC）是由感染EBV的GC细胞增殖所定义。单个GC中EBV阳性和阴性成分共存的情况罕见。我们报告一例GC同时存在EBV阳性和阴性成分的病例，在此病例中，我们首次进行了各种分子分析以阐明其组织发生。
一名81岁男性根据内镜检查结果和活检标本的病理检查被诊断为GC。由于根据计算机断层扫描诊断出有淋巴结和肺转移，遂进行了全身化疗。化疗后，在确认转移淋巴结大小减小且肺转移消失后，进行了全胃切除术和淋巴结清扫术。大体上，一个3型肿瘤位于胃体中后部。在切面处，肿瘤由肿瘤肛门侧的白色实性部分和口腔侧的扁平隆起部分组成。组织学上，前一部分由伴有淋巴间质的GC组成，后一部分由无明显淋巴细胞浸润的低分化腺癌组成。这两个组织病理学成分彼此明显分开。在EBV编码的小RNA（EBER）原位杂交（ISH）中，伴有淋巴间质成分的部分呈阳性，而另一部分呈阴性。免疫组织化学显示，两个成分均显示p53过表达。使用从两个成分中提取的DNA对TP53进行测序，结果显示出不同的模式。靶向二代测序显示肿瘤的EBV阳性成分中有MYC扩增，EBV阴性部分中有HER2扩增。免疫组织化学显示EBV阳性部分为C-MYC（+）/HER2（-），EBV阴性部分为C-MYC（-）/HER2（+）。相应地，显色ISH和双色ISH显示EBV阳性部分有C-MYC扩增且无HER2扩增，EBV阴性部分无C-MYC扩增且有HER2扩增。
我们展示了一例由EBER-ISH（+）/C-MYC（+）和EBER-ISH（-）/HER2（+）细胞组成的两种不同GC碰撞的病例。
