Pancreas and Gall bladder pathology

Question 1

What does the following image show? (Hint: it’s healthy tissue)

Answer 1

Exocrine component of the pancreas

Question 2

What does the image show? (Hint: it is healthy tissue)

Answer 2

Endocrine component of the pancreas

Question 3

1. What is acute pancreatitis?
2. Risk factors

Answer 3

1. Acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes.
2. Alcohol and drugs

Question 4

What are the causes of acute pancreatitis?

Answer 4

Duct obstruction:

• Gall stones (50%)
• Trauma
• Tumours

Metabolic/toxic:

• Alcohol (33%) - 5% of alcoholics develop acute pancreatitis
• Drugs e.g. thiazide
• Hypercalcemia (acute pancreatitis with other causes can cause hypocalcaemia)
• Hyperlipidemia

Poor blood supply:

• Shock
• Hypothermia

Infection/inflammation:

• Viruses (Mumps, which is a virus that affects glands, so can affect glands in the pancreas)
• Autoimmune
• Idiopathic (15%)

Question 5

Describe the pathogenesis of duct obstruction, and how it can lead to acute pancreatitis

Answer 5

Gallstone stuck distal to where the common bile duct and pancreatic duct joins leads to reflux of the bile up the pancreatic duct followed by damage to acini and release of proenzymes which then become activated.

Alcohol leads to spasm/oedema of Sphincter of Oddi and the formation of the protein rich pancreati fluid which obstructs the pancreatic ducts

Question 6

What type of injury to the pancreas does infection/inflammation cause? (everything apart from duct obstruction)

Answer 6

Direct acinar injury

Question 7

Acute pancreatitis: patterns of injury:

Describe the patterns of injury ofthe following and what causes it

1. Periductal
2. Perilobular
3. Panlobular

Answer 7

1. Periductal - necrosis of acinar cells near ducts (usually secondary to obstruction)
2. Necrosis at the edges of the lobules (usually due to poor blood supply
3. Panlobular - develops from 1 and 2

Question 8

Describe the pathogenesis of injury to the periductal and periorbital areas of the pancreas

Answer 8

Activated enzymes –> acinar necrosis –> enzyme release etc.

Ranges from stromal oedema, to haemorrhagic necrosis

e.g. Lipases –> fat necrosis - calcium ions bind to free fatty acids forming soaps wihc are seen as yellow-white foci

Question 9

Describe the following regarding acute pancreatitis:

1. Complications
2. Prognosis

Answer 9

1.Complications:

• Pancreatic - pseudocyst (an accumulation of fluid without an epithelial lining), abscess
• Systemic - shock, hypoglycemia, hypocalcemia

2. Prognosis:
   * Overall mortablity up to 50% for haemorrhagic pancreatitis

Question 10

What does this image show?

Answer 10

Fatty deposition in the pancreas in acute pancreatitis

Question 11

What is chronic pancreatitis?

Answer 11

Relapsing or persistent inflammation of the pancreas, associated with acute pancreatitis

Question 12

Why are many cases of chronic pancreatitis linked to acute pancreatitis?

Answer 12

Mild acute pancreatitis can heal itself and regenerate. Very bad acute pancreatitis can lead to chronic pancreatitis and long term damage leading to persistent/chronic pancreatitis

Question 13

What are the causes of chronic pancreatitis?

Answer 13

Metabolic/toxic:

• Alcohol (80%)
• Haemachromatosis - Fe desposited in the pancreas, affecting both exocrine and endocrine components

Duct obstruction:

• Gallstones
• Abnormal pancreatic duct anatomy
• Cystic fibrosis “mucoviscoidosis”

Tumours

Idiopathic - autoimmune

Question 14

1. What is the pathogenesis of chronic pancreatitis?
2. What is the pattern of injury for chronic?

Answer 14

1. Same as acute pancreatitis - obstruction or metabolic components can lead to release of enzymes causing necrosis and inflammation of the pancreas
2. chronic inflammation, as in 1, with parenchymal fibrosis and loss of parenchyma. Duct strictures withe calcified stones occur, causing secondary dilatations

Question 15

What are the complications of chronic pancreatitis?

Answer 15

• Malabsorption
• Diabetes mellitus
• Pseudocysts (which can lead to abscess formation so need to be removed)
• Carcinoma of the pancreas

Question 16

What does this image show?

Answer 16

Pancreatic calcifications - diagnostic of chronic pancreatitis

Question 17

What does this image show?

Answer 17

Chronic pancreatitis: only islets left behind, everything else has been destroyed. Fibrosis and loss of parenchymal tissue

Question 18

What is a pancreatic pseudocyst?

Answer 18

• Associated with acute and/or chronic pancreatitis
• Lined by fibrous tissue (no epithelial lining), contain fluid rich in pancreatic enzymes or necrotic material
• Connect with pancreatic ducts
• May resolve, compress adjacent strctures, become infected or perforate

Question 19

What is IgG4 related disease?

Answer 19

`Autoimmune pancreatitis

Characterised by a large numbers of IgG4 positive plasma cells

May involve the pancreas, bile ducts and almost any other part of the body

Responds very well to steroid therapy

Question 20

What tumours can develop in the pancreas and what cellss are affected?

Answer 20

Carcinomas:

• Ductal (85% of all neoplasms) - most cancers are ductal
• Acinar

Acinar ductal metaplasia - is an important pathway for pancreatic cancer - derived from acinar but become ductal tissue

Cystic neoplasms:

• Serous cystadenoma
• Mucinous cystic neoplasm

Pancreatic neuroendocrine tumours - Islet cell tumours

Question 21

What is the epidemiology of Ductal carcinoma of the pancreas?

Answer 21

• 5% of cancer deaths
• Increasingly common with age, 2:1 male:female
• 5 year survival: 5%

Question 22

What are the risk factors for Pancreatic carcinoma?

Answer 22

• Smoking
• BMI and dietary factors
• Chronic pancreatitis
• Diabetes

Question 23

Describe the pathogenesis of Ductal carcinoma

Answer 23

Ductal carcinomas arise from dysplastic ductal lesions:

• Pancreatic Intraductal Neoplasia (PanIN)
• K-ras mutations in 95% of cases

Question 24

Describe the pathology of Ductal carcinomas

1. Macroscopic appearance
2. Microscopic appearance

Answer 24

Macroscopic appearance:

• Gritty and grey
• Invades adjacent structures
• Tumours in the head present earlier

Microscopic appearance

Adenocarcinomas:

• Mucin secreting glands set in desmoplastic stroma

Question 25

What does this image show? What in this is characteristic of this condition?

Answer 25

* Adenocarcinoma of the pancreas * Nerve wrapping itself around the tumour, which is peri-neural invasion - very characteristic of pancreatic cancer

Question 26

What are the main sites for ductal carcinomas?

Answer 26

* Head (60%) * Body * Tail * Diffuse Follows the anatomy This is the reverse for neuroendocrine tumours

Question 27

Describe the spread/where the spread of ductal carcinoma is for the following: 1. Direct 2. Lymphatic 3. Blood 4. Serosa

Answer 27

1. Direct --\> Bile ducts. duodenum (movement of pancreatic secretions) 2. Lymphatic --\> lymph nodes 3. Blood --\> liver (portal system) 4. Serosa --\> Peritoneum

Question 28

What are the complications of Ductal carcioma?

Answer 28

* Commonly complications are due to spread - e.g. liver and Jaundice * Chronic pancreatitis * Venous thrombosis (migratory thrombophlebitis) - pancreatic cancer cancer diagnosed late, lots of cancer cells causes mets are in the blood. These produce mucin/mucous which trigger the coagulation cascade in the blood causing clotting

Question 29

What are cystic tumours?

Answer 29

Tumors that contain serous or mucin secreting epithelium Usually benign

Question 30

Describe Pancreatic endocrine neoplasms

Answer 30

* Usually non-secretory * Contain neuroendocrine markers e.g. chromogranin - which is a blood screening test for NETs * Behaviour is difficult to predict * May be associated with MEN1

Question 31

What is an insulinoma? What is there a high risk of?

Answer 31

* Insulinomas - tumors deriving from the beta cells of the pancreas - which secrete insulin causing increased secretion of insulin * commonest type of secretory tumor * High risk of hypoglycemia

Question 32

Where are NETs most commonly found in the pancreas?

Answer 32

The tail of the pancreas (opposite to carcinomas of the pancreas)

Question 33

What does this image show? What are they commonly seen in?

Answer 33

Rosette cells Common pathological presentation of NETs

Question 34

What are the main problems that can occur in the gall bladder (3)?

Answer 34

* Gall stones * Inflammation * Cancer

Question 35

What percentage of adults in the West have cholelithaiasis?

Answer 35

20% of adults in the West have gallstones

Question 36

What are the risk factors for gall stones?

Answer 36

* Age and gender- increasing age, F\>M * Ethnic and geographic e.g. Native Americans * Hereditary e.g. disorders of bile metabolism * Drugs e.g. Oral contraceptive pill * Acquired disorders e.g. rapid weight loss

Question 37

What are the different types of gall stones? Which ones are radiolucent, and which ones are radioopaque?

Answer 37

* Cholesterol - more than 50% of all gall stones. These may be single, mostly radiolucent * Pigment - containing calcium salts of unconjugated bilirubin. There are often multiple, and most of them are radioopaque

Question 38

What are the complications of Gall stones?

Answer 38

* Bile duct obstruction * Acute and chronic cholecystitis * Gall bladder cancer * Pancreatitis However, many with gallstones are asymptomatic

Question 39

What is acute cholecystitis? Most common cause?

Answer 39

Acute cholecystitis is acute inflammation of the gall bladder 90% associated with gall stones

Question 40

What is chronic cholecystitis? What happens/forms?

Answer 40

* Chronic inflammation of the gall bladder * Development of fibrosis and diverticula - called Rokitansky-Aschoff sinuses. These diverticula develop due to obstruction and overworking - same as diverticula develop in the colon * 90% contain gall stones

Question 41

What cancer occurs in the gall bladder? What are 90% of gall bladder cancer associated with?

Answer 41

Adenocarcinomas 90% associated with gall stones

Question 42

What is cholangiocarcinoma? Where is it common?

Answer 42

Cholangiocarcinoma is cancer of the bile ducts, and can develop from advanced gallbladder cancer Not so common in the UK, but commonest in South America