Gastric carcinoma harbouring loss‑of‑function mutations in the , and genes exhibits diverse histological features associated with EBV infection and inactivation: A case report.

This study presents a novel case of gastric carcinoma (GC) with diverse histological features and unique molecular alterations. A 62-year-old man with hematemesis was diagnosed with advanced GC and hepatic metastasis. Despite palliative gastrectomy to control bleeding, the patient succumbed within 6 months. Histological examination revealed three distinct tumour components: Gastric adenosquamous carcinoma (GASC), GC with lymphoid stroma (GCLS) and poorly differentiated adenocarcinoma (PDAD). Immunohistochemical staining, next-generation sequencing and Epstein-Barr virus (EBV) hybridisation were performed to characterise the tumour. The GASC component revealed diffuse p40 and p63 immunoreactivity, while the GCLS and PDAD components were negative for both markers. All components harboured a missense mutation in the phosphoinositide-3-kinase regulatory subunit 1 gene and deletions in the and RNA binding motif protein 10 genes. Additionally, the GCLS component was EBV positive and the PDAD component demonstrated concurrent EBV infection and inactivation. The present case highlights the importance of thorough molecular and histological evaluation, as distinct molecular alterations and heterogenous EBV status in histologically diverse components may significantly influence patient prognosis and treatment strategies.