Genetic, immunohistochemical, and clinical features of medullary carcinomaof the pancreas - A newly described and characterized entity

Medullary carcinomas of the pancreas are a recently described, histological ly distinct subset of poorly differentiated adenocarcinomas that may have a unique pathogenesis and clinical course. To further evaluate these neoplas ms, we studied genetic, pathological, and clinical features of 13 newly ide ntified medullary carcinomas of the pancreas. Nine (69%) of these had wild- type K-ras genes, and one had microsatellite instability (MSI). This MSI me dullary carcinoma, along with three previously reported MSI medullary carci nomas, were examined immunohistochemically for Mlh1 and Msh2 expression, an d all four expressed Msh2 but did not express Mlh1, In contrast, all of the medullary carcinomas without MSI expressed both Msh3 and Mlh1. Remarkably, the MSI medullary carcinoma of the pancreas in the present series arose in a patient with a synchronous but histologically distinct cecal carcinoma t hat also had MSI and did not express Mlh1. The synchronous occurrence of tw o MSI carcinomas suggests an inherited basis for the development of these c arcinomas. Indeed, the medullary phenotype, irrespective of MSI, was highly associated with a family history of cancer in first-degree relatives (P < 0.001), Finally, one medullary carcinoma with lymphoepithelioma-like featur es contained Epstein-Barr virus-encoded RNA-1 by in situ hybridization, The refore, because of medullary carcinoma's special genetic, immunohistochemic al, and clinical features, recognition of the medullary variant of pancreat ic adenocarcinoma is important. Only by classifying medullary carcinoma as special subset of adenocarcinoma can we hope to further elucidate its uniqu e pathogenesis.