Molecular Pathology of Pancreatic Tumors

Abstract

Neoplasms of the pancreas exhibit a vast array of morphologic and clinical features, ranging from benign proliferations to the deadliest cancers. The normal pancreas is composed of distinct cellular compartments, and these compartments provide a broad framework for morphological classification of pancreatic neoplasms. This morphologic classification divides pancreatic neoplasms into distinct groups with diverse clinical and molecular features. On a molecular level, pancreatic neoplasms occur due to the accumulation of mutations in oncogenes and tumor suppressor genes that transform a normal pancreatic cell through various neoplastic precursors into invasive neoplasm. The specific genes affected by these molecular alterations vary based on the type of neoplasm—for example, the genes altered in infiltrating ductal adenocarcinomas are quite different from those altered in pancreatic neuroendocrine tumors or acinar cell carcinomas, illustrating that each pancreatic neoplasm possesses a distinct profile of genetic changes. These unique molecular alterations form a basis for specific diagnostic tests to discriminate pancreatic neoplasms, and molecular analyses of clinical samples show promise in further advancing the diagnosis and treatment of pancreatic neoplasms.