4例伴淋巴样间质胃癌的临床病理特征OA

Objective:Gastric carcinoma with lymphoid stroma(GCLS)is a rare subtype of gastric carcinoma.It is mainly associated with Epstein-Barr virus(EBV)infection or deficient mismatch repair(dMMR)/microsatellite instability-high(MSI-H)status and exhibits distinctive molecular characteristics and an immune microenvironment.This study aims to retrospectively analyze the clinicopathological and molecular features of 4 cases of GCLS,explore its key diagnostic features,molecular subtypes,and potential for immunotherapy,and thereby improve clinicians'and pathologists'understanding of this tumor and provide a reference for individualized treatment. Methods:Four cases of GCLS diagnosed in the Department of Pathology,The First Medical Center of Chinese PLA General Hospital,between October 2021 and May 2022 were collected.Their clinical data,histopathological features,and characteristics of the immune microenvironment were retrospectively analyzed.Immunohistochemistry(IHC)was performed to assess the expression of mismatch repair(MMR)proteins,including post-meiotic segregation increased 2(PMS2),MutL homolog 1(MLH1),MutS homolog 2(MSH2),and MSH6,as well as human epidermal growth factor receptor 2(HER2),cluster of differentiation 4(CD4),CD8,and programmed death-ligand 1(PD-L1,clone SP263).Epstein-Barr virus-encoded small RNA(EBER)in situ hybridization was used to determine EBV infection status.Next-generation sequencing(NGS)was performed to detect point mutations,insertions/deletions,gene fusions,and copy-number amplifications in 40 tumor-related genes,including EGFR,KRAS,PIK3CA,and ERBB2,and microsatellite instability(MSI)status was also assessed. Results:Among the 4 patients with GCLS,3 were men and 1 was a woman.The patients were 56−72 years old at diagnosis.Tumors were located in the gastric body in 2 cases,the gastric fundus in 1 case,and the fundus-body junction in 1 case.Histologically,all tumors were poorly differentiated carcinomas.The tumor cells were oval to polygonal and arranged in nests and sheets,with prominent stromal lymphocytic infiltration(50%−80%).Lymphoid follicle formation was observed in some cases,and occasional cases showed lymphovascular tumor emboli and perineural invasion.Based on the molecular and IHC findings,the 4 cases could be classified into 2 molecular subtypes.Three cases were EBER-positive/pMMR/MSS and all harbored PIK3CA mutations,accompanied respectively by MAP2K1,ERBB2 plus CTNNB1,and PTEN mutations.HER2 was predominantly negative or showed low expression,whereas PD-L1 expression was high.The remaining case was EBER-negative/dMMR/MSI-H,harbored a KRAS p.G12D mutation,and showed loss of MLH1,PMS2,and MSH6 expression.The CD8/CD4 ratio was>1 in all cases,indicating a T-lymphocyte-rich tumor microenvironment. Conclusion:GCLS is a rare subtype of gastric carcinoma with distinctive histopathological and molecular features.It can be broadly divided into 2 molecular subtypes:the EBER-positive/pMMR/MSS subtype,characterized predominantly by PIK3CA mutations,and the EBER-negative/dMMR/MSI-H subtype,which may harbor KRAS mutations and loss of MMR protein expression.Both subtypes show high PD-L1 expression and prominent lymphocytic infiltration,suggesting that patients with GCLS may potentially benefit from immunotherapy.