Introduction

Pancreatic cancer is usually fatal. Various factors have been ascribed to this grim reality, including the lack of early disease detection methods and the poor response of pancreatic patients to therapies (1,2). Surgery is the only curative therapy (Figure 48.1), but only a small minority of patients qualify for surgery (10–20%) and most of these patients still succumb to local or metastatic recurrence. In advanced disease, chemotherapy remains the only option, however few agents are approved and they show only a modest survival benefit. To make progress against this cancer, a better understanding at the molecular and tissue level is urgently required, which should serve as a “roadmap” to identify better therapeutic agents.

Histopathology of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is the most common exocrine pancreatic tumor, accounting for 85% of all malignant pancreatic tumors. Histologically, PDA is a malignant epithelial neoplasm which demonstrates gland formation (3). A characteristic feature of PDA is the intense peritumoural desmoplastic reaction (Figure 48.1). PDA evolves through a multi-step process with cells gaining cumulative genetic and phenotypic alterations resulting in pathological progression from normal pancreas to pre-invasive pre-neoplasms and invasive cancer (4; Figure 48.2). These pre-neoplasms include pancreatic intra-epithelial neoplasms (PanINs), intra-ductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs). Compelling evidence supports the notion that PDA develops from pancreatic pre-neoplasms, similar to the proposed adenoma–carcinoma sequence in colorectal adenocarcinoma (5).