The pancreas is made up of three populations of epithelial cells, each of which can give rise to a tumour:
- acinar cells, which produce digestive enzymes and make up more than 80% of the volume of epithelial cells
- ductal cells, which line the ducts that carry those enzymes, and make up 10–15% of epithelial cells
- islet endocrine cells, which produce hormones such as insulin, and make up 1–2% of epithelial cells
Despite this, more than 95% of pancreatic cancers arise from the exocrine part of the pancreas — the acinar and ductal cells — and have the features of an adenocarcinoma. The ductal cells, though they account for a small fraction of the gland by volume, are the origin of the great majority of these cancers.
Ductal adenocarcinoma
Ductal adenocarcinoma is the most common pancreatic tumour, accounting for 85–90% of all pancreatic tumours. It arises most often in the head of the pancreas, in about 70% of cases; the tail accounts for 15–20% and the body for about 10%. This distribution matters clinically, because the head of the pancreas sits next to the bile duct and the duodenum, so a tumour there tends to cause symptoms — jaundice, or obstruction of the duodenum — much earlier than a tumour in the body or tail, which has room to grow silently. That difference in timing is why head tumours are more often resectable and body and tail tumours present late.
Under the microscope, ductal adenocarcinomas are graded by how closely they still resemble normal duct tissue:
- Well-differentiated tumours form glandular structures, show mild cellular atypia, have few mitoses and produce mucin.
- Moderately differentiated tumours are intermediate on these features.
- Poorly differentiated tumours lose the glandular arrangement, show marked cellular atypia and increased mitoses, and no longer produce mucin.
Local spread and metastasis
Because of its position, a head-of-pancreas tumour spreads in a characteristic way. It can obstruct the common bile duct and the pancreatic duct, causing jaundice and, when the pancreatic duct is blocked, exocrine pancreatic insufficiency with malabsorption; some tumours invade the duodenum or the ampulla of Vater. Almost all head-of-pancreas tumours also invade the retroperitoneal space behind the pancreas, involving the portal vein, the superior mesenteric vessels and nerves, the splenic flexure of the colon, the stomach, the spleen and the left adrenal gland. This local invasion — particularly of the major vessels — is what usually makes a tumour unresectable.
When the disease is diagnosed at an advanced stage, it has often already metastasised. The common sites are the liver, regional lymph nodes and peritoneum; less common sites include bone, lung and pleura.