Collision of Lymphoepithelioma-like Carcinoma with Diffuse Large B-cell Lymphoma of the Stomach: A Case Report

Discussion

EBV can cause many types of carcinoma, including GC. EBV-associated GC includes two subtypes, including gastric LELC and ordinary gastric adenocarcinoma (1). Non-Hodgkin lymphoma mainly includes B cell lymphoma (DLBCL and MALT) and very few T-cell lymphomas. Collision of EBV-associated GC with gastric non-Hodgkin lymphoma is extremely rare. According to the previous reports, five cases of EBV-associated GC with GL have been reported (2-6).

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Figure 2.

Micrographs demonstrating gastric LELC positive immunohistochemical staining for (A) CK1/CK3, (B) CD20, (C) CD3 and (D) CD38; (E) approximately 67% of the tumor cells were positive for Ki67; and (F) in situ hybridization for EBER was positive.

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Figure 3.

Micrographs demonstrating gastric primary DLBCL positive immunohistochemical staining for (A) CD20, (B) LCA/CD45, (E)CD10, (F) Bcl-6 and negative for (C) CD3, (D) Bcl-2, (G) Mum-1; (H) approximately 90% of the tumor cells were positive for Ki67; and (I) in situ hybridization for EBER was negative.

This report described a rare case of a patient suffering from two different tumors. One was in the proximal stomach, which consisted of many poorly differentiated carcinomas with a dense lymphocytes and plasma cells infiltrating. The second tumor was an ulcer type, which was located at the distal stomach. Tumor cells had formed many lymphoepithelial lesions and had invaded the submucosa and muscularis of the stomach. As these tumor cells were positive for CD10 and Bcl-6 but negative for Mum-1, it was identified as a primary DLBCL (7). As 90% of the tumor cells expressed Ki-67, it suggests that the cells were fast growing and so was diagnosed as a high-degree malignant lymphoma.

Most of the carcinoma cells of gastric LELC were positive for EBER, suggesting that the virus infection happened in the early stages of tumorigenesis. The infected, malignantly transformed cells formed the tumor after monoclonal proliferation. The lymphoma cells were negative for EBER, suggesting that the pathogenesis of DLBCL was independent from LELC. We could not however, exclude a relationship between the two tumors. Firstly, the two tumors were present simultaneously in the stomach and the infiltrating lymphocytes of LELC can continuously stimulate other tumors and lead to deteriorating (3). Secondly, infection by Helicobacter pylori (H. pylori) can cause GC and GL. H. pylori infection can cause chronic active gastritis, intestinal metaplasia, ulcers, GC, MALT and DLBCL (8). However, in this case, H. pylori was not detected, so we speculated that the infection of H. pylori had nothing to do with the emergence of the two malignancies. Thirdly, in the pathogenesis of gastric LELC, chronic persistent inflammation plays an important role (1, 4). Wong et al., reported that an environment with an active inflammation and immunosuppression contributed to the occurrence of EBV positive lymphomas which were promoted by an inflammatory or immunosuppressive microenvironment (9). In this report, the gastric mucosa of the patient also had chronic gastritis.

So far, the pathogenesis of the collision of multiple tumors is not clear. There may be many factors involved in its pathogenesis. Besides the infection of pathogenic microorganisms (EBV and H. pylori), many other risk factor may also be involved, such as genetic susceptibility and environmental factors. Genetic susceptibility may play an important role. For example, loss of chromosomes, gene insertion or mutation of chromosome are related with DLBCL (10) and human epidermal growth factor receptor 2 (EGFR2) abnormalities are associated with gastric cancer, breast cancer and other tumors (11, 12). Previous case reports have not shown any special genetic aberration accounting for the multiple malignancies. For future work, we would like to examine molecular genetic abnormalities existing in multiple malignancies and to study their detailed roles. Environmental factors, such as smoking, eating habits and drinking, may be involved in the pathogenic process (12, 13). Age may also play a role in the process of tumorigenesis, whilst most of the cases of multiple malignancies reported have happened in elderly people (14). This is consistent with our case which happened in a 65-year-old patient.

In conclusion, we report a rare case of collision of gastric LELC and DLBCL in one patient. It is unknown if infection by pathogenic microorganisms, population age, environmental pollution has contributed to the coexistence of multiple tumors in one patient, though it may happen more frequently than before. The pathogenesis of DLBCL was independent from LELC, but it may be triggered by the immune response caused by infection.