Pathology of the pancreas

Question 1

List and explain the congenital anomalies of the pancreas

Answer 1

Agenesis
- Failure to develop
- Have been associated with IPF1 gene mutations on chromosome 13q12.1

Pancreas divisum
- Most common clinically significant anomaly
- When the foetal duct systems of the pancreatic primordia fail to fuse

Annular pancreas
- The outcome is a ring of pancreatic tissue that completely encircles the duodenum

Ectopic pancreas
- Occur in 2% of population
- Favoured sites are the stomach and duodenum, followed by the jejunum, Meckel diverticulum and ileum.

Congenital cysts
- Probably result from anomalous ductal development

Question 2

Define acute pancreatitis

Answer 2

Reversible pancreatic injury associated with inflammation
Ranging from oedema and fat necrosis to parenchymal necrosis with severe haemorrhage

Question 3

What are the causes of acute pancreatitis

Answer 3

Billiary tract disease and alcoholism
Obstruction of pancreatic duct
Medications
Infections
Metabolic
Vascular injury
Trauma
Inherited genetic defects

Question 4

Explain how pancreatic duct obstruction could lead to acute pancreatitis

Answer 4

• Gallstone or biliary sludge in ampulla result in increased intraparenchymal ductal pressure
• Accumulation of enzyme rich interstitial fluid
• Although most pancreatic enzymes are secreted in inactive form, lipase is produced in active form and has the potential to cause local fat necrosis

Question 5

Explain how primary acinar cell injury could lead to acute pancreatitis

Answer 5

Acinar cells damaged by
* Oxidative stress
– Generate free radicals in acinar cells, leading to membrane lipid oxidation and the activation of transcription factors, including AP1 and NF-κB, which in turn induce the expression of chemokines that attract mononuclear cells

• Increased calcium flux trigger inappropriate activation of digestive enzymes
  – activation of trypsinogen to trypsin is favored

Question 6

Explain how defective intracellular transport of proenzymes within acinar cells can lead to acute pancreatitis

Answer 6

In normal acinar cells, digestive enzymes and lysosomal hydrolases are transported in separate pathways

If defective
* Proenzyme activation and release of enzymes

Question 7

Define the following:
- Acute interstitial pancreatitis
- Acute necrotizing pancreatitis
- Haemorrhagic pancreatitis

Answer 7

Acute interstitial pancreatitis:
–Mild inflammation, interstitial oedema and focal areas of fat necrosis in the pancreas and the peri pancreatic fat

Acute necrotizing pancreatitis
– Necrosis of acinar and ductal tissues aswell as islets of Langerhans

Haemorrhagic pancreatitis
– Extensive necrosis and haemorrhage

Question 8

Define chronic pancreatitis

Answer 8

Characterised by longstanding inflammation and fibrosis of the pancreas with destruction of the exocrine pancreas

The chief distinction between acute and chronic pancreatitis is the irreversible impairment in pancreatic function in chronic pancreatitis

Question 9

What are the causes of chronic pancreatitis

Answer 9

Long standing alcohol abuse

Long standing pancreatic duct obstruction
Tropical pancreatitis
Hereditary pancreatitis
Chronic pancreatitis associated with CFTR mutations

Question 10

Explain autoimmune pancreatitis

Answer 10

Pathogenically distinct form of chronic pancreatitis associated with IgG4 - secreting plasma cells in the pancreas

One manifestation of IgG related disease which may involve multiple tissues

Question 11

Explain the morphology of pancreatic pseudocysts

Answer 11

Formed by walling-off of areas of haemorrhagic fat necrosis with fibrous tissue

Central necrotic haemorrhagic material rich in pancreatic enzymes surrounded by non epithelial lined fibrous walls of granulation tissue

Question 12

Explain pancreatic carcinoma and risk factors thereof

Answer 12

It progresses from non neoplastic epithelium, to non invasive lesions in small ducts, to invasive carcinoma

Risk factors include:
- Smoking
- Diet rich in fat
- Increased risk with chronic pancreatitis
- DM
- Familial clustering

Question 13

Explain the morphology of pancreatic carcinoma

Answer 13

Usually hard, stellate, gray-white, poorly defined
Highly invasive
Involvement of peripancreatic lymph nodes – Often liver metastases

Anaplastic cuboidal to columnar epithelium

Question 14

Describe pancreaticoblastoma in terms of:
- Defintion
- Macroscopy
- Microscopy

Answer 14

*Definition:
- Most common pancreatic tumor of infancy / early childhood
- Characterized by acinar differentiation, squamoid corpuscles and stromal bands

Macroscopy
- Partially encapsulated, often lobulated, mean diameter10 cm

Microscopy
- Mixtures of acini, squamoid corpuscles and less commonly endocrine or ductal features