Ductal Adenocarcinoma of the Pancreas


Incidence, age of onset, gender, geography


Pancreatic cancer is the 9th most common cancer (incidence of 6/100,000 per year). It is almost universally fatal (1-2% 5 year survival).

Age of Onset

The incidence of pancreatic carcinoma increases with age, doubling every decade after 40. It is very uncommon before the age of 40.


Slightly more men than women are affected (1.5:1).


Pancreatic cancer is much more common in Western countries.


Lifestyle rather than genetic factors are thought to be of most importance. This observations comes from the higher rates of disease in ethnic groups that have migrated to Western countries versus those in their home country.


Risk factors for developing pancreatic cancer include:

  • Smoking - double or triple the risk
  • Obesity
  • Chronic pancreatitis - alcohol does not directly impact on the development of pancreatic cancer except in cases where chronic pancreatitis develops
  • Exposure to ionising radiation
  • Occupational exposure - exposure to chlorinated hydrocarbons (eg. metalwork)

Caffeine exposure was once thought to be a risk but this has been excluded.

Germline mutations can also increase the risk of pancreatic cancer:

  • BRCA2: 4-10 fold increase in risk
  • Peutz-Jeghers: 130 fold increase in risk


Pancreatic cancer is thought to develop through multiple pre-malignant stages. Each stage is characterised by the activation or inactivation of particular genes. Premalignant lesions are called Pancreatic Intraepithelial Neoplasias (PanINs). The typical stages are:

  • PanIN-1: Activation of k-RAS and shortening of telomeres
  • PanIN-2: Loss of p16
  • PanIN-3: Loss of TP53, SMAD4, BRCA2

This hypothesis is supported by the presence of PanINs adjacent to malignant tumours and a similar distribution of PanINs to malignancies (more common in the pancreatic head).

Natural History

The distribution of pancreatic cancer within the gland is as follows:

  • Head: 60%
  • Body: 15%
  • Tail: 5%
  • All areas: 20%

Pancreatic cancer typically causes no symptoms until it is locally advanced. Symptoms generally occur when adjacent structures are invaded, by which time the tumour is usually unresectable. Tumours of the body typically invade adjacent retroperitoneal structures, including the superior mesenteric vessels, portal vein and coeliac plexus. Lymphatic spread is common, and depends on the site of the tumour.

  • Pancreatic head tumours usually spread to local lymph node groups (pancreato-duodenal and pancreatic head groups). Further spread may occur to the coeliac nodes, porta hepatis, superior mesenteric nodes and para-aortic nodes.
  • Tumours of the body and tail are usually more locally advanced at diagnosis. Lymphatic spread occurs to nodal groups above and below the body and tail as well as the splenic hilum.

Haematogenous spread is most commonly to the liver followed by the lungs. Other sites include the adrenal glands, bone metastases, kidney, brain and skin.

Clinical Presentation


Many pancreatic carcinomas are asymptomatic in early, resectable stages. Symptoms only occur once adjacent structures are invaded. Tumours of the head can cause obstructive jaundice by occluding the common bile duct. Pain occurs with invasion of the coeliac plexus or other adjacnet structures. Advanced cases lead to weight loss, anorexia, and fatigue; these are more common with tumours of the body or tail as they cause fewer early symptoms.
An unusual symptom is migratory thrombophelbitis; also known as Trousseau’s sign. Patients develop thrombophelebitis at various sites around the body. This is due to the production of coagulating factors by the tumour. It occurs in about 10% of patients.


On general examination patients may appear cachetic and/or jaundiced. On abdominal examination, the liver may be enlarged due to metastases. Large pancreatic tumours may be palpable.


Standard bloods should be performed (FBE/UEC/CMP/LFT); the most important results are the LFTs which may indicate liver metastases.
The Ca 19.9 is the most relevant tumour marker. It is not sensitive or specific enough to be used in routine practice but may support a diagnosis of pancreatic cancer if highly elevated. It can also be used to monitor the effectiveness of therapy in patients with elevated levels.


There are several essential imaging tests.

CT Abdomen

Contrast CT remains the 'gold standard' test for pancreatic cancer. It allows evaluation of the primary tumour, involvement of adjacent vessels, and detection of liver metastases. Ultrasound is less accurate than CT and MRI is not superior. PET scanning has also been plagued by poor sensitivity for lymph node metastases and poor differentiation between tumour and pancreatitis.


ERCP is a useful test in patients with suspicion of pancreatic cancer (eg. painless jaundice) but with equivocal or negative findings on CT. Stenting can be performed at the time of ERCP if surgery will be delayed.

Endoscopic Ultrasound

EUS is a newer technique that allows accurate evaluation of the vessels adjacent to the tumour and also allows pre-operative diagnosis of pancreatic cancer.

Other Staging Investigations

Because of the terrible prognosis of pancreatic cancer, and the inability of modern tests to detect all cases of locally advanced disease (20-30%), laparoscopic staging prior to laparotomy is performed in some centres. This spares patients futile surgery and improves their palliation.

Tumour Features


Tumours are white to tan, often with ill-defined borders. They are usually larger in the body or tail than in the head.


Tumours form duct-like and glandular structures separated by desmoplastic stroma. Normal pancreatic tissue may be preserved. Less-well differentiated tumours usually have smaller glandular structures which may be incomplete. Sheets of cells are only seen in poorly differentiated tumours. Mitotic activity and pleomorphism increase with loss of differentiation.


Staining for cytokeratins allows differentiation of ductal adenocarcinoma from acinar adenocarcinoma as well as intestinal adenocarcinoma. The typical pattern for ductal adenocarcinoma is CK 7 +ve and CK 20 -ve. Acinar adenocarinoma stains negatively for both and intestinal adenocarcinoma positive for both.

Rare Variants

  • Adenosquamous carcinoma consists of the standard ductal adenocarcinoma with regions of squamous epithelium.
  • Undifferentiated carcinoma consists of spindle cells
  • Mucinous non-cystic carcinoma contain over 50% mucin but does not form a cyst.


Pancreatic tumours are classified by the TNM system. Stage I and II are resectable, stage III is unresectable, and stage IV is metastatic.

T Stage

  • Tis: Carcinoma in situ, including PanIN 1-3
  • T1: Limited to pancreas, < 2 cm
  • T2: Limited to pancreas, > 2 cm
  • T3: Extension beyond pancreas, no involvement of coeliac axis or superior mesenteric artery
  • T4: Involvement of coeliac axis or superior mesenteric artery

N Stage

  • N1: Regional lymph node metastases

M stage

  • M1: Distant metastases

Final Stage

Stage T N M
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1-3 N1 M0
III T4 NAny M0
IV TAny NAny M1