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Case of the Month: November 2021

posted: November 1, 2021

This is a 72-year-old female with past medical history of diabetes who presented with black stool and iron deficiency anemia. Upper endoscopy was performed and showed large friable soft mass located in the gastric body with slight atrophy of the background gastric mucosa. Subtotal gastrectomy was performed and shows an 8 cm polypoid gastric mass along the great curvature in the background of slightly atrophic gastric mucosa.

A panel of immunostains is performed and shows that the tumor cells are negative for CK7, CK20, CDX2, synaptophysin, SOX10, arginase and SALL4. INI and BRG1 are both intact. Mismatch repair proteins are intact. Links to cytokeratin (AE1/E3) and EBV in-situ hybridization are below.

View Final Diagnosis
Final Diagnosis: EBV- associated gastric carcinoma
From the molecular standpoint, gastric carcinomas can be classified into a gnomically stable, microsatellite instable, chromosomal instable and Epstein-Barr virus-associated carcinomas. The latter is a distinct subtype that accounts for nearly 10% of gastric carcinomas. It is defined by the presence of latent EBV infection in the tumor cells and can be detected by identifying the Epstein–Barr virus-encoded small RNAs (EBERs) localized in the nucleus of tumor cells infected with the virus. Epidemiologically, they are more common in male patients and usually affects the proximal portion of the stomach and carries a better prognosis. The tumor can form an ulcer or a polypoid mass that can even be multiple. Histologically, the tumor cells can either show predominance of lymphocytic infiltration within the stoma, a pattern known as carcinoma with lymphoid stroma, or a conventional adenocarcinoma, although there is a morphological continuum between these types. Tumor cells are positive for keratin and EBER in-situ hybridization. The molecular imprint of EBV associated gastric carcinoma shows high level of DNA hypermethylation but absence of MLH1 hypermethylation and usually a higher level of PD-L1 expression which can be utilized as a therapeutic option for the management of this type of gastric tumors.
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Update on Epstein-Barr virus and gastric cancer. Int J Oncol 2015 Apr;46(4):1421-34.
Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517): 202–209.