T11-L4: Pancreatic Pathology

Question 1

What enzyme is raised in pancreatitis and therefore used as a marker?

Answer 1

Amylase

Question 2

What is the most common aetiology of acute pancreatitis? Give other causes.

Answer 2

• Gallstones (50%)
• Alcohol (25%)
• Idiopathic (10%)

Rare causes (<5%)

• Vascular insufficiency
• Viral infection - mumps, coxsackie B
• Hypercalcaemia
• ERCP - Endoscopic Retrograde Cholangiopancreatography
• Inherited causes

Question 3

Give hereditary causes of pancreatitis.

Answer 3

• SPINK 1 Gene - autosomal recessive - trypsin inhibitor that prevents autoactivation. Any abnormality in this gene can result in pancreatitis.
• PRSS1 inherited mutations - autosomal dominant. This is essential for the inactivation of trypsin. As a result, activation of trypsin leads to activation of other enzymes leading to pancreatitis.

Question 4

What are the clinical features if acute pancreatitis?

Answer 4

• Usually presents as an emergency requiring admission to hospital
• Sudden onset of severe abdominal pain radiating to back
• Nausea and vomiting
• May be mild (recovery within 5-7 days) but can be serious with high mortality
• Raised serum amylase/lipase (>3x normal)
• Persistent hypocalcemia is a poor prognostic sign

Question 5

What is Grey Turner’s sign?

Answer 5

In severe pancreatitis the gland becomes swollen and fat necrotic and haemorrhagic - this then spreads to the subcutaneous tissue of the flank presenting with superficial bruising in the fat around the flank.

Question 6

What is Cullen’s sign?

Answer 6

Superficial bruising in the subcutaneous fat around the umbilicus in pancreatitis.

Question 7

Why do we see hypocalcaemia in pancreatitis?

Answer 7

It is caused primarily by precipitation of calcium soaps in the abdominal cavity, but glucagon-stimulated calcitonin release and decreased PTH secretion may play a role.

Fatty acids binds calcium and so it leads to hypocalcaemia, hyperglycaemia, abscess formation due to necrosis and pseudocysts (filled with pancreatic juice without epithelial lining).

Question 8

What are possible complications of acute pancreatitis?

Answer 8

• Shock
• Intravascular coagulopathy
• Haemorrhage
• Pseudocysts

Question 9

Why can chronic pancreatitis be mistaken for carcinoma?

Answer 9

Fibrosis of exocrine tissue can mimic carcinoma macroscopically and microscopically. It is hard therefor to distinguish between tumor and fibrotic exocrine tissue. This is progressive inflammatory disorder in which parenchyma of pancreas is destroyed and replaced by fibrous tissue. There is irreversible destruction of the exocrine tissue, followed by destruction of the endocrine tissue.

Question 10

Why is diabetes a late stage complication of chronic pancreatitis?

Answer 10

The endocrine glands after the exocrine glands.

Question 11

Give the aetiology of chronic pancreatitis?

Answer 11

• Toxics such as alcohol, smoking, drugs, hypercalcaemia, hyperparathyroidism, inceptions
• Idiopathic
• Genetic - cystic fibrosis gene, PRSS1, SPINK-1
• Autoimmune
• Recurrent acute pancreatitis
• Obstruction of the main duct - cancer, scarring

Question 12

What are calculi in chronic pancreatitis associated with?

Answer 12

Alcohol

Question 13

Give complications of chronic pancreatitis.

Answer 13

• Malabsorption of fat (lack of lipases)
  • Steatorrhoea - foul swelling stool, difficult to flush away
  • Impairment of fat soluble vit absorption –A,D, E and K
  • Diarrhoea, weight loss and cachexia
• Diabetes (late feature) as the endocrine component is destroyed much later than the exocrine component
• Pseudocysts (10% patients)
• Stenosis of common bile duct/duodenum
• Severe chronic pain

Mortality rate - nearly 50% with 20-25 years of disease onset.

Question 14

What is the main cancer of the pancreas?

Answer 14

Pancreatic ductal adenocarcinoma - it accounts for 3% of all cancers. The 5YSR is 4%. It tends to affect those 60-7- years and has a slight male predominance.

Question 15

Give Hereditary Pancreatic Cancer syndromes?

Answer 15

Account for 5-10%

• Lynch syndrome
• Familial Atypical Multiple Mole Melanoma (FAMMM)
• HER
• Ataxia-telangiectasia
• Hereditary pancreatitis
• Peutz-Jeghers

Question 16

Where do most cancers occur in the pancreas?

Answer 16

60-70% in the head of the pancreas

Question 17

How does pancreatic cancer present?

Answer 17

Early cancer is silent, It is present for at least a decade before detection. They can present with:

• Non-specific symptoms -epigastric pain, radiating to back
• Weight loss, painless jaundice, pruritis and nausea.
• Trousseau’s syndrome (migratory thrombophlebitis) and Courvoisier’s sign (palpable gallbladder without pain)**
• Distant metastases (liver, peritoneum, lung)
• Diabetes – increases risk and can be a presenting complication (late feature)

Question 18

How does pancreatic cancer affect surrounding tissues?

Answer 18

• Perineural invasion is common in pancreatic cancer
• Cancers in pancreatic head cause stenosis and proximal dilatation of common bile duct and main pancreatic duct (double duct sign on imaging). They can present with obstructive chronic pancreatitis due to upstream atrophy of non-neoplastic tissue. They then present with jaundice.
• Most infiltrate surrounding structures – ampulla of Vater, duodenal wall, peripancreatic and retroperitoneal tissues, superior mesenteric vessels.
• Cancers in the body or tail can invade the stomach, left side of colon, spleen and left adrenal. They present with few signs and symptoms. They do not present with jaundice.

Question 19

What is the difference between Pancreatic neuroendocrine tumours and neuroendocrine carcinomas?

Answer 19

Neuroendocrine tumours:

• Well differentiated
• mild to moderate cellular Atypica
• No necrosis
• Slow growing
• Functioning or non-functioning (60%)
• 5YSR 33%, 10YSR 17%

Neuroendocrine carcinoma: 
- Poorly differentiated
- Highly atypical cells 
- Necrosis present 
- Fast growing 
rarely survive 1 year 90% present with metastasis 
- usually non-functioning

Question 20

What clinical findings do we see in the following neuroendocrine neoplasms:

(a) Insluinoma
(b) Glucagonoma
(c) Gastrinoma
(d) Somatostatinoma
(e) VIPoma
(f) PP-cell PEN

Answer 20

a) Hypoglycaemia
(b) Stomatitis (inflammation of the mouth and lips), rash, diabetes and weight loss
(c) Known as Zollinger-Elison syndrome - peptic ulcer and diarrhoea. Gastrin, which stimulates the stomach to secrete acid and enzymes.
(d) Diabetes, Cholelithiasis (gallstones), Hypochlorhydria (low levels of gastric acid)
(e) The cell type involved is unknown. Known as Verner-Morrison syndrome - presents with diarrhoea. hypakalcaemia, achlorhydria
(f) Neoplasm of the PP cells. Presents with no clinical syndrome.

Question 21

Where do neuroendocrine tumours metastasise to?

Answer 21

Mets can occur many years after primary tumor. Initially, regional lymph nodes and liver, later lung and bone.