Molecular Pathology of Pancreatic Cancer

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 sequential accumulation of mutations in oncogenes and tumor suppressor genes that transform a normal pancreatic cell through various precursors into a neoplastic cell, often with malignant potential. The specific genes affected by these molecular alterations vary based on the type of neoplasm—for example, the genes altered in ductal adenocarcinoma are quite different from those altered in pancreatic neuroendocrine tumors or acinar cell carcinoma, illustrating that each pancreatic neoplasm possesses a distinct profile of genetic changes. These unique molecular alterations provide 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.