Pancreatic pathology

Question 1

Pancreatitis definition

Answer 1

• Inflammation (itis) of the pancreas; associated with injury to the exocrine parenchyma
• Acute: gland reverts to normal if underlying cause removed
• Chronic: irreversible loss of the pancreatic tissue

Question 2

Hereditary Pancreatitis

Answer 2

• PRSS1 inherited mutations: autosomal dominant - Mutations result in trypsin being resistant to cleavage by another trypsin molecule
• SPINK1 gene: autosomal recessive - codes for trypsin inhibitor which helps prevent autodigestion of pancreas by activated trypsin

Question 3

SPINK1 gene

Answer 3

serine protease inhibitor Kazal type 1

Question 4

Acute Pancreatitis aetiology + epidemiology

Answer 4

• Gallstones: 50% cases, Alcohol: 25% cases

- 1M: 3F in biliary disease, 6M: 1F alcoholism

Question 5

Acute Pancreatitis clinical features

Answer 5

• Sudden onset of severe abdominal pain radiating to back
• Nausea and vomiting
• Raised serum amylase/lipase (>3x normal)
• Persistent hypocalcaemia is a poor prognostic sign

Question 6

Acute Pancreatitis pathogenesis

Answer 6

• Obstruction by stones damages duct lining resulting in leakage and activation of pancreatic enzymes- Amylase into blood
• Fat gets in due to trauma - resulting in swollen, necrotic gland with fat necrosis and haemorrhage
• Hypocalcaemia: fatty acids bind calcium ions, hyperglycaemia, abscess formation, pseudocysts

Question 7

Acute Pancreatitis complications

Answer 7

• Intravascular coagulopathy, DIC
• Haemorrhage
• Pseudocysts: collections of pancreatic juice secondary to duct rupture

Question 8

Chronic Pancreatitis definition

Answer 8

• Progressive inflammatory disorder where parenchyma of pancreas destroyed and replaced by fibrous tissue
• Irreversible destruction of the exocrine tissue followed by destructions of the endocrine tissue

Question 9

Chronic Pancreatitis aetiology: TIGARO

Answer 9

• Toxic: alcohol, cigarette smoke, drugs, hypercalcaemia, hyperparathyroidism infections
• Idiopathic
• Genetic CFTR: cystic fibrosis gene, PRSS1, SPINK 1 mutations
• Autoimmune
• Recurrent acute pancreatitis
• Obstruction of main duct: cancer, scarring

Question 10

Chronic Pancreatitis pathogenesis

Answer 10

• Ductal obstruction by protein plugs

- Direct toxic effects from alcohol include - dilated and distorted ducts, calculi

Question 11

Chronic Pancreatitis complications

Answer 11

• Leads to malnutrition and diabetes
• Intermittent abdominal pain, back pain and weight loss
• Mortality rate - nearly 50% with 20-25years of disease onset
• Malabsorption of fat (lack of lipases)

Question 12

Pancreatic Adenocarcinoma epidemiology

Answer 12

• Most common type of pancreatic cancer: up to 90% of all pancreatic neoplasms
• 60-80yrs, 1.3Male: 1 female
• Location = 60-70% head, 5-15% body, 10-1% tail
• If in head = Jaundice

Question 13

Pancreatic Adenocarcinoma aetiology

Answer 13

• Cigarette smoking: 20% of cases, 2-3x risk
• Family history: 10% cases
• heavy alcohol intake, diet rich in red meats, obesity

Question 14

Pancreatic Adenocarcinoma progression model

Answer 14

• MCN = in body of pancreas, mimic ovarian tissue which progress to cancer
• IPNN = intraductal – main duct or side branches, chance of development to cancer depends on where cysts are – if in side branches they don’t
• PanIN = most common neoplastic precursor to invasive pancreatic cancer, starts in duct

Question 15

Pancreatic Intraepithelial Neoplasia (PanIN)

Answer 15

• 60-70% head of pancreas
• Grossly – hard, grey-white, poorly defined masses
• Highly invasive and elicits a “desmoplastic response”
• Desmoplastic response: intense non-neoplastic host reaction composed of fibroblasts, lymphocytes and extracellular matrix

Question 16

Pancreatic Neuroendocrine Tumours features

Answer 16

• Uncommon <3% pancreatic neoplasms
• Derived from islet cells
• From benign to malignant
• 20-60 years; M=F

Question 17

Well differentiated neuroendocrine tumour

Answer 17

• 1-2% all pancreatic neoplasms; any age but rare in children
• 15-35% non-functioning – not producing a certain hormone
• Single tumours often produce multiple hormones but usually single hyperfunctional syndrome

Question 18

Poorly differentiated neuroendocrine carcinomas

Answer 18

• Males > Females, 40-75 years
• Advanced disease at presentation
• Prognosis without treatment 1-2 months, with chemotherapy up to 50 months
• Rare; < 1% of all pancreatic tumour

Question 19

Insulinoma

Answer 19

• Small tumour in the pancreas that produces an excess amount of insulin
• Produces hypoglycaemia due to hypersecretion of insulin
• Patient develops confusion, psychiatric disturbance, possibly coma, potential permanent cerebral damage

Question 20

Pancreatic Neuroendocrine Tumours appearance

Answer 20

• Usually well circumscribed, sometimes encapsulate, solid or cystic
• 10->50mm