Gullo Irene, Sacramento Maria Luísa, Morais Rui, Kim Yongsoo, Eijk Paul P, Rocha Ana Mafalda, Baptista Diana, Santos-Antunes João, Ylstra Bauke, Carneiro Fátima
Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal.
Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.
Virchows Arch. 2025 Jan 28. doi: 10.1007/s00428-025-04035-3.
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.
本病例报告描述了一例罕见的双表型胃癌，其具有两种不同但克隆相关的组织学成分。第一种成分与爱泼斯坦-巴尔病毒（EBV）感染相关，表现出伴有淋巴间质的胃癌形态学特征，提示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显著的免疫反应。第二种成分EBV阴性，呈管状/乳头状形态，具有生物学侵袭性增加的特征，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，但两种成分均为克隆相关，EBV阴性区域显示出更复杂的DNA畸变，类似于染色体不稳定（CIN）病变。本病例描述了单一胃癌内克隆相关的EBV阳性和阴性成分，有助于更好地理解EBV在肿瘤异质性和进展中的作用，并突出了EBV缺失对肿瘤行为的影响。
