Carcinomas with Lymphoid Stroma within the Gastrointestinal Tract: Histology and Molecular Pathology

Carcinomas with lymphoid stroma represent a distinct morphological subtype of gastrointestinal cancer. They occur most often in the stomach or in the colon. On the morphological level, they may be separated into medullary and lymphoepithelioma-like cancers. The former are characterized by predominantly syncytial growth and dense lymphocytic infiltration that prevails at the tumour periphery. Lymphoepithelioma-like cancers are made up of small clusters and aggregates of tumour that are broken up by large numbers of intratumoural lymphocytes. Differential diagnosis may be challenging and often requires immunohistochemistry. Several markers are often necessary to separate medullary colon carcinoma from poorly differentiated non-medullary carcinoma, as the immunophenotypes are overlapping. Diagnosis of gastrointestinal carcinoma with lymphoid stroma should always prompt further investigations, aiming at the detection of EBV infection and MSI-H. The majority of carcinomas with lymphoid stroma occurring in the stomach are lymphoepithelioma-like cancers. On the molecular level, these cancers are positive for EBV. In the colon medullary cancers prevail. They occur most often as right-sided lesions. These tumours almost invariably show high level microsatellite instability (MSI-H) due to sporadic epigenetic silencing of the MLH-1 gene.