해외 증례Multiple Epstein-Barr Virus-associated Gastric Cancers Arising in a Patient with Autoimmune Gastritis

관리자
2023-10-04
조회수 64

Suzuki Y, et al. Intern Med. 2023 May 15;62(10):1459-1466. 

doi: 10.2169/internalmedicine.0673-22. 

Epstein-Barr virus (EBV)는 위암을 포함한 다양한 종양 발생과 연관성이 알려져 있으며, 위암의 경우 약 10%에서 EBV가 확인되고 있습니다. 위암과 동시에 발생하는 EBV-associated GC (EBVaGC)에 대한 incidence는 아직 충분히 알려져 있지 않습니다. 

EBVaGC과 H. pylori 사이의 연관성은 충분히 알려져 있지 않으나, EBVaGC와 Hp infection에 의한 chronic inflammation 사이에는 두 가지 면에서 연관성을 보이는데, EBVaGC의 발생률의 증가는 lymphocytic infiltration에 의해 심한 영향을 받는 atrophic border에서 발생하며 non-atrophic mucosa 보다는 atrophic mucosa에서 EBV-DNA detection rate가 훨씬 높습니다. 그리고, EBV와 Hp 의 감염이 동시에 되어 있으면 위암 발생률이 높다고 알려져 있는데, Hp에 의한 gastric epithelium의 chronic inflammation은 polyclonal DNA의 비 정상적인 methylation을 유도하게 되는데 EBV infection 또한 광범위한 methylation의 원인으로 알려져 있습니다. 이러한 mechanisms이 EBVaGC에 대한 높은 methylated epigenotype과 관련이 있다고 볼 수 있습니다. 또한, EBV infection에 의해 Hp에 의한 cytotoxin 연관 gene의 antigens 분비를 증가 시키기도 합니다. 

AIG의 경우도 chronic inflammation을 일으키는 원인으로 DNA methylation과 carcinogenic risk를 증가시키는 것으로 알려져 있으며 EGVaGC 사이의 연관성은 알려진 바가 없습니다. 이번 case는 AIG 환자에서 발생한 다발성 EBVaGCs에 대한 report 질환 발생의 다양성에 대해 설명하고자 합니다. 


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69세/Male


Table 1. Hematological and Biochemical Laboratory Data and Serological Tests.


Figure 1. Atrophic gastritis of the entire stomach, a typical finding in autoimmune gastritis, was observed (a, b). Gastric carcinoma was detected in the posterior wall of the upper gastric body (lesion 1) and middle gastric body (lesion 2). Lesion 1 was a reddish elevated lesion measuring 40 mm (c). Lesion 2 was a reddish elevated lesion measuring 20 mm (d). Magnifying endoscopy with narrow-band imaging revealed that both lesions 1 (e) and 2 (f) had an irregular microvascular pattern. Endoscopic ultrasound detected a hypoechoic lesion in the first and second of five layers corresponding to the intramucosal layer. No disruption or thinning of the third layer (yellow arrowhead) was observed in lesion 1, suggesting that the tumor remained in the mucosal layer (g). 


Figure 2. Findings on a histological examination of synchronous lesions 1 and 2. Photomicrographs (×100) of lesion 1 (a) and lesion 2 (b) with Hematoxylin and Eosin staining. EBV-encoded small RNA was detected by in situ hybridization in lesion 2 (c). Photomicrographs (×200) of the background gastric mucosa (d-f). Atrophic changes of fundic glands with pseudopyloric metaplasia, linear hyperplasia of ECL cells and endocrine cell micronests were detected in the background gastric mucosa (d). Endocrine cell micronests were shown to be positive for synaptophysin (e) and chromogranin A (f). 


Figure 3. Findings on white-light endoscopy and magnifying endoscopy with narrow-band imaging for metachronous gastric cancers (yellow arrowhead): lesions 3 (a, b), 4 (c, d), 5 (e, f), and 6 (g, h). An endoscopic lace pattern was observed in lesions 3 (b) and 5 (f) (blue arrowhead). 


Figure 4. Findings on a histological examination of metachronous lesions 3 (a, b), 4 (c, d), 5 (e, f) and 6 (g, h). Photomicrographs (×100) of lesions 3-6 with Hematoxylin and Eosin staining (a, c, e, g), and EBV-encoded small RNA in situ hybridization, (b, d, f, h). Almost all carcinoma cells in the tumor were stained for EBV-encoded small RNA. 


Table 2. Synchronous and Metachronous Gastric Cancer. 


Abstract: 

Epstein-Barr virus-associated gastric cancer (EBVaGC) has been reported to be associated with chronic inflammation of the gastric epithelium caused by Helicobacter pylori infection. Autoimmune gastritis (AIG) is also believed to increase the risk of carcinogenesis. We herein report a case of multiple EBVaGCs that arose in a patient with AIG, highlighting the potential for multiplicity of this entity. In this case, a total of four metachronous EBVaGCs were found after initial Endoscopic submucosal dissection for EBVaGC, all of which were treated endoscopically. This case demonstrates that patients with AIG should be monitored closely for development of EBVaGC. 

Key words: Epstein-Barr virus, gastric cancer, endoscopic submucosal dissection

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