gastric carcinoma with lymphoid stroma

Gastric carcinoma with lymphoid stroma (medullary carcinoma) is one of the uncommon subtypes. It occurs more commonly in proximal stomach and generally follows a less aggressive clinical course.

Histologically, this type of carcinoma is characterized by a sharply demarcated advancing margins composed of irregular nests or sheets of polygonal tumor cells associated with a prominent lymphoid infiltrate in a non-desmoplasticstroma.

It is interesting that over 80% of gastric carcinomas with lymphoid stroma are Epstein-Barr virus (EBV) positive (26,27), and EBV is only identified in the malignant and dysplastic cells but not in the normal epithelial cells@<@code>@<@/code>.

The finding has raised the hope for tumor cell targeting, especially after studies show that Bortezomib, a proteasome inhibitor, can induce EBV kinase by activating EBV lytic protein expression in the infected tumor cells, which in turn renders the infected cells more susceptible to killing by other agents.

Another group of gastric carcinomas with lymphoid stroma are those that demonstrate high microsatellite instability, resulting from defective function of DNA mismatch repair proteins, usually hMLH1 or hMSH2, but rarely hMSH6.

The number of tumor-infiltrating lymphocytes, while significantly higher than the one in non-microsatellite instability-high cancers, is lower than that in EBV positive carcinoma.

This group of carcinoma is usually intestinal type by Lauren’s classification, and often affects the elderly, with a lower pTNM stage and a low risk of lymph node metastasis. It was suggested that microsatellite instability-high status and EBV infection were the variables which rendered the carcinoma a better prognosis.

However, the claims have not been substantiated by other studies. More recent study reveals that the high number of tumor-infiltrating lymphocytes is the only favorable prognostic factor independent of EBV infection and microsatellite instability-high status.

Also in this investigation, neither EBV positivity nor microsatellite instability-high alone was proved to be an independently favorable prognostic factor. Interestingly, EBV positivity and microsatellite instability-high status, while both share the feature of prominent tumor-infiltrating lymphocytes, are rarely concomitant, suggesting the two are unrelated and involved in distinct underlying pathways in carcinogenesis.