Epstein-Barr virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review.

IF 3.1 3区医学 Q1 PATHOLOGY Virchows Archiv Pub Date : 2026-03-01 Epub Date: 2025-01-28 DOI:10.1007/s00428-025-04035-3

Irene Gullo, Maria Luísa Sacramento, Rui Morais, Yongsoo Kim, Paul P Eijk, Ana Mafalda Rocha, Diana Baptista, João Santos-Antunes, Bauke Ylstra, Fátima Carneiro

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Abstract

This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with the EBV-negative area showing more complex DNA aberrations, reminiscent of chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and -negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlights the impact of EBV loss on tumour behaviour.

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Epstein-Barr病毒状态驱动胃癌肿瘤内形态学和分子异质性：来自病例报告和文献综述的见解

本病例报告描述了一个罕见的双表型胃癌的情况下，两种不同的，但克隆相关，组织学成分。第一个成分与eb病毒（EBV）感染相关，表现出胃癌伴淋巴样基质的形态学特征，表明EBV作为一种有效的免疫原性因子，可能在肿瘤微环境中引发突出的免疫反应。第二部分为ebv阴性，显示管状/乳头状形态，生物侵袭性增强，如高级别区域和淋巴浸润。免疫组织化学和分子研究证实，尽管形态和免疫表型不同，但这两种成分都是克隆相关的，ebv阴性区域显示出更复杂的DNA畸变，让人想起染色体不稳定（CIN）病变。本病例描述了单个胃癌中EBV阳性和阴性的克隆相关成分，有助于更好地理解EBV在肿瘤异质性和进展中的作用，并强调了EBV丢失对肿瘤行为的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virchows Archiv 医学-病理学

CiteScore

7.40

自引率

2.90%

发文量

204

审稿时长

4-8 weeks

期刊介绍： Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.