Histopathology 7 - Diseases of the pancreas and gall bladder Flashcards
Recall the mnemonic for the causes of acute pancreatitis
I GET SMASHED
Idiopathic (15%)
Gallstones (50%)
Ethanol (33%)
Trauma
Steroids
Mumps
Autoimmune
Scorpion sting
Hyperlipidaemia/hypercalcaemia/hyperparathyroidism
ERCP
Drugs
Recall two causes of pancreatitis via duct obstruction
Gallstones Alcohol (via spasm/ oedema of Sphinter of Oddi)
Recall the pathophysiology of injury seen in acute pancreatitis
- Enzymes activated
- Acinar necrosis
- Enzyme release
Can cause anything from stromal oedema to haemorrhagic necrosis (**coagulative necrosis)
What are the 3 patterns of injury that may be seen in acute pancreatitis?
Periductal (necrosis of acinar cells near ducts) - caused by obstruction
Perilobular (necrosis at the edges of lobules) - caused by poor blood supply
Panlobular (develops from either of the above)
Why are yellow/white foci seen in acute pancreatitis?
Lipases cause fat necrosis
Calcium ions bind to free fatty acids forming soaps (which are white yellow)
What is a pseudocyst?
Dilated space with no epithelial lining
A psuedocyst can increase the chances of having an abscess
What is a cyst?
Dilated space lined by epithelium
Recall 2 pancreatic and 3 systemic complications of acute pancreatitis
Pancreatic: pseudocyst + abscess
Systemic: shock, hypoglycaemia, hypocalcaemia
Recall 4 complications of chronic pancreatitis
Malabsorption
Diabetes mellitus
Pseudocysts
Carcinoma of the pancreas
What is contained within a pancreatic pseudocyst?
Pancreatic enzymes and necrotic material (which is why it’s so bad when they perforate - it causes peritonitis)
Causes of chronic pancreatitis- what is the most common?
- Metabolic/ Toxic (2):
a) ALCOHOL (80%)
b) Haemochromatosis- iron overload (bronzed diabetes) - Duct Obstruction (3):
a) Gallstones
b) Abnormal pancreatic duct anatomy
c) Cystic fibrosis (mucoviscoidosis) - Tumours
- Idiopathic
- Autoimmune
DIfference in pathology between acute and chronic pancreatitis
Pattern of Injury- distinguishes chronic pancreatitis from acute pancreatitis:
Chronic inflammation with:
parenchymal (functional tissue) fibrosis
→ loss of parenchyma
Duct strictures with:calcified stones
→ secondary dilatations
Histology of chronic pancreatitis:
- no acini
- fibrous tissue
- remaining ducts and islets of langerhans are prominent
Complications of chronic pancreatitis
Malabsorption (exocrine dysfunction)
Diabetes mellitus- fibrosis can overwhelm the islets of langerhans → DM
Pseudocysts, abscess
Pancreatic calcifications
Carcinoma of the pancreas
Which immunoglobin is implicated in autoimmune acute pancreatitis?
IgG4
What type of cancer makes up 85% of pancreatic neoplasms?
Ductal carcinoma
What are the different types of pancreatic tumour?
Carcinomas:
- Ductal
- Acinar
Cystic neoplasms:
- Serous cystadenomas
- Mucinous cystic neoplasms
Pancreatic neuroendocrine tumours (Islet cell tumours)
What mutation is very common in ductal carcinoma?
K-Ras
Tumour marker of pancreatic cancer
CA-19-9
Risk factors for pancreatic ductal carcinoma
smoking
BMI and dietary risk factors
Chronic pancreatitis
Diabetes
What are the 2 types of precancerous dysplastic ductal lesions in the pancreas?
- PanIn (pancreatic intraductal neoplasm)
- Intraductal mucinous papillary neoplasm
**remember PanIn
Which type of tumour has a “gritty and grey” macroscopic appearance?
Ductal adenocarcinoma
What is the typical microscopic appearance of ductal carcinoma of the pancreas?
Mucin-secreting glands set in desmoplastic stroma
stroma that arises in response to cancer - makes it hard and gritty
Define adenocarcinoma
Mucin-secreting glands set in desmoplastic stroma (means: strong stromal reaction)
Recall 3 complications of ductal carcinoma
- Liver metastasis
- Chronic pancreatitis
- Venous thrombosis (“migratory thrombophlebitis”/ Trousseau syndrome) = mucin activating coagulation in circulatory system causing thrombosis
Which type of pancreatic tumours are usually benign?
Cystic tumours
WHich part of the pancreas are serous cystadenomas found in?
The head
Which type of pancreatic tumour is likely to contain neuroendocrine markers?
Are these tumours secretory or non-secretory?
Pancreatic endocrine neoplasms
**most are non-secretory
Recall a neuroendocrine marker in pancreatic endocrine neoplasms
Chromogranin
Which type of pancreatic tumour is associated with MEN1?
Pancreatic endocrine neoplasms
What is the most common type of secretory pancreatic tumour?
Insulinomas
In which portion of the pancreas are neuroendocrine tumours most common?
Tail
What are the 2 types of gallstone?
Cholesterol- mostly single, mostly radiolucent
Pigment-mostly multiple, mostly radio-opaque
*can also get mixed stones - these are the most common
What do pigment gallstones contain?
Calcium salts of unconjugated bilirubin
Risk factors for gallstones
1) Acquired disorders (e.g. rapid weight loss- body tries to remove all the cholestrol that it has been storing)
2) Ethnic factors can contribute (e.g. Native Americans have a very high incidence of gallstones)
3) Hereditary factors (e.g. disorders of bile metabolism)
4) Drugs (e.g. oral contraceptive)\
5) age and gender: increasing age, F>M
Which type of gallstones are radiolucent/radio opaque
Cholesterol: radiolucent (i.e. appear white on x-ray)
Pigment: radio-opaque (i.e. appear black on x-ray)
Recall 4 potential complications of gallstones
Pancreatitis- acute or chornic (mostly acute)
Bile duct obstruction
Cholecystitis
Gall bladder cancer
What is the most common cause of acute cholecystitis?
Gallstones (accounts for 90%)
What is a key histopathological finding in chronic cholecystitis?
Diverticula Rokitansky-Aschoff sinuses
What is the most common cause of gallbladder cancer?
Gallstones
**rmb gallbladder cancer is very rare
What is IgG4 related disease?
A type of autoimmune disease that may affect the pancreas, surrounding structure or pretty much anywhere else in the body
What type of cancer can lead to cholangiocarcinoma?
Gallbladder cancer
Where does pancreatic duct join?
Joins the common bile duct which drains into the duodenum
Endocrine and exocrine components of the pancreas
Endocrine: islets of langherhans
Exocrine: acini and ducts
What has better prognsois: cholangiocarcinoma or pancreatic cancer?
Cholangiocarcinoma
Defnition of acute pancreatitis
- acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes
- so essentially the pancreas damages itself with the pancreatic enzymes
- Relatively common, incidence is increasing
What is the most common cause of pancreatitis?
Gallstones
Pathogenesis of acute pancreatitis?
obstruction
- gallstone gets stuck distal to where the pancreatic duct joins the common bile duct –> bile refluxes back into the pnacreatic duct –> damage to acini–> release of proenzymes–> autodigestion
- alcohol can also cause obstructive damage - leads to spasm of sphincter of oddi and formation of protein rich substance which can cause obstruction
- but main mechanism of alcohol causing pancreatitis is via direct chemical injury
direct acinar injury
everything else
Which complication of pancreatitis renders the worst prognosis?
Haemorrhagic necrotic pancreatitis
mortality is 50% due to risk of shock
Two types of chronic pancreatitis
Relapsing or persistent
What is the precursor of chronic pancreatitis?
Acute pancreatitis - chornic pancreatitis is assoictaed with thsi in about 50% of cases.
Mild acute pancretaitis tends to resolve quickly but severe acute pancreatitis risks progressing to chornic pancreatitis
Causes of chronic pancreatitis
- Alcohol - most common cause (as opposed to acute pancreatitis where alcohol causes 1/3 of cases)
- Haemochromatosis - bronzed diabetes (damage to pancreas causes diabetes)
- duct obstruction
- cystic fibrosis (mucoviscoidosis)
- tumours - cause obstruction
- idiopathic
- autoimmune
Pattern of injury in chronic pancreatitis
Chronic inflammation with panrechymal fibrosis and loss of parenchyma
Duct strictures with calcified stones with secondary dilatations
**damage to acini as well as the ducts
Complications of chronic pancreatitis
- malabsorption
- diabetes - presents later as exocrine damage is before endocrine damage
- pseudocyst
- pancreatic cancer
x ray appearance of chronic pancreatitis
calcified stones in pancreas
What lines pseudocysts?
fibrous tissue
not lined by epithelium like pancreatic cysts
What do pancreatic pseudocysts contain?
Fluid rich in pancreatic enzymes or necrotic material
What do panreatic pseudocysts connect to?
Pancreatic ducts
When do you usually get pancreatic pseudocysts?
Post-surgical
Progression of pseudocysts including complications
- May resolve
- May compress adjacent structures
- May become infected → abscess
- May become infected → perforate:
- necrotic material rich in activated enzymes leaks into peritoneal cavity
- acute peritonitis
Which parts of the body does IgG4 disease affect?
Pancreas, bile ducts and almost any other part of the body
Histology of IgG4 disease
duct is surrounded by loads of IgG4 expressing plasma cells
Treatment of IgG4 disease
Respond well to steroids
Precursor lesions of pancreatic ductal carcinoma
- PANIN - pancreatic intraductal neoplasia
- intraductal mucinous papillary neoplasm
Which type of pancreatic tumour (location) presents earlier and therefore has better prognosis?
Tumour of the head of the pancreas
Most common site of pancreatic cancer
Head
How does ductal carcinoma of the pancreas spread?
DIRECT: bile ducts, duodenum
LYMPHATIC: lymph nodes (celiac lymph nodes)
BLOOD: liver
SEROSA/ CAVITIES: peritoneum
NERVES: celiac plexus
Complications of ductal adenocarcinoma
- Pancreatic cancers cause obstruction → Chronic pancreatitis
- Complications due to spread
- Venous thrombosis (migratory thrombophlebitis):
- This is because circulating pancreatic cancer cells release mucous into bloodstream
- → activates clotting cascade
Where are neuroendocrine tumours of the pancreas commonly found?
Tail (unlike adenocarcinoma)
Are neuroendocrine tumours secretory or non-secretory?
What is the most common secretory tumour?
Mostly non-secretory
Insulinomas are the most common secretory tumour
Presentation of neuroendocrine tumours
- Diabetes
- Epigastric mass
- Hepatosplenomegaly
- NOT jaundice
- because tail of the pancreas not the head
Presentation of inulinomas
hypoglycaemia
What is the most common cause of chronic cholecystitis?
Gallstones
Role of secretin and CCK
Secretin: produced by s-cells of the duodenum, controls gastric acid secretion and buffering with HCO3-
CCK: responsible for stimulating digestion of fat and protein. Made by I-cells in the duodenum. Causes release of digestive enzymes.
**these stimulate pancreas to produce enzymic fluid
What scoring system is used for acute pancreatitis?
Glasgow score
>3= severe pancreatitis
Most sensitive marker for acute pancreatitis
Amylase- transient increase
Serum lipase is the most sensitive!!
Acinar cell carcinoma
What is trousseau syndrome?
Recurrent superficial thrombophlebitis
What is a gastrinoma?
Causes zollinger-ellison syndrome –> high acid output –> reucurrent ulceration
**tumour of the G cells in pancreas or duodenum**
Men1
pituitary- adenoma
parathyroid- adenoma
pancreas - endocrine tumour
MEN2A
parathyroid
thyroid (medullary thyroid carcinoma)
phaeo
MEN2B
medullary thyroid
phaeo
neuroma
marafnoid (men2B- b for big)
How many g. of glucose given for OGTT?
75g
