Histopath - Pancreas and gall bladder

Question 1

What is the histology of the pancreas

Answer 1

Exocrine: ducts and ascini, protease, amylase, lipase
Endocrine: islets of langerhans for glucagon, insulin and somatostatin

Question 2

Define acute pancreatitis

Answer 2

Acute inflammation caused by aberrant release of pancreatic enzymes

Question 3

What are the causes of acute pancreatitis

Answer 3

(Idiopathic 15%)
Gallstones (50%)
Ethanol (33%)
Steroids
Mumps
Autoimmune
Scorpion bite
Hyper-calcaemia/-lipidaemia
ERCP
Drugs (thiazides)

Duct obstruction: gallstones, trauma, tumours
Metabolic/toxic: alcohol, drugs, hypercalcaemia, hyperlipidaemia
Poor blood supply : shock, hypothermia
Infection/inflammation: viruses e.g. mumps

Question 4

What is the role of calcium in acute pancreatitis

Answer 4

Can be a be a cause (hypercalcaemia)

Also CAUSES hypocalcaemia
Lipases released → fat necrosis → FFAs → binds the free calcium → reduced free calcium (saponification) → yellow-white foci; so, if this is the cause, calcium drops to a NORMAL level in the acute phase

Question 5

What is the pathogenesis of acute pancreatitis

Answer 5

Duct obstruction: gallstones become stuck distal to the the connection between the common bile duct and pancreatic duct → reflux of bile up the pancreatic duct → release of pro-enzymes → activated → damage to the acini
Alcohol → spasms/oedema of the sphincter of Oddi and formation of protein-rich pancreatic fluid → duct obstruction
Ranges from stromal oedema to haemorrhagic necrosis

Direct acinar injury

Question 6

What are the patterns of injury in acute pancreatitis

Answer 6

peri-ductal: necrosis of acinar cells near the ducts (usually secondary to obstruction)

Peri-lobular: necrosis at the edges of the lobules (usually due to poor blood supply)

Pan-lobular: this will develop from worsening of either periductal or perilobular inflammation

Question 7

What are the complications of acute pancreatitis

Answer 7

Pancreatic: pseudocyst formation (collection of fluid without epithelial lining) → infection → abscess
Systemic: shock, hypoglycaemia, hypocalcaemia

Question 8

What is the prognosis for acute pancreatitis

Answer 8

Dependent on severity
Mortality of 50% for haemorrhagic pancreatitis

Question 9

What are the histological features of acute pancreatitis

Answer 9

Macroscopically: Yellow nodules (foci fat necrosis)
Microscopically: blue areas = calcium, coagulative necrosis

Question 10

What are the features of chronic pancreatitis

Answer 10

Relapsing or persistent
Associated with acute pancreatitis in about half of cases (scarring)
Relatively uncommon
Mortality of 3% per year

Question 11

What are the causes of chronic pancreatitis

Answer 11

Metabolic/toxic: ALCOHOL, haemochromatosis
Duct obstruction: gallstones, abnormal pancreatic duct anatomy, cystic fibrosis “mucoviscoidiosis”
Tumours
Idiopathic: autoimmune

Pathogenesis is the same as acute pancreatitis

Question 12

What are the patterns of injury in chronic pancreatitis

Answer 12

Chronic inflammation with parenchymal fibrosis and loss of parenchyma (ascini become atrophic)
Duct strictures with calcified stones with secondary dilatations (calcification = diagnostic of chronic pancreatitis)

Question 13

What are the complications of chronic pancreatitis

Answer 13

EARLY: Malabsorption (occurs much earlier as lipases, etc. are not produced)
LATE: Diabetes mellitus (late stage as endocrine parts survive much longer than exocrine components)
Pseudocysts
Carcinoma of the pancreas (?)

Question 14

What is the histology of chronic pancreatitis

Answer 14

Macro: scarring, pale tissue, cyst formation
Micro: Fibosis (pale pink), islets behind. Acini atrophy → depletion, calcification, duct dilatation with thick secretions

Question 15

What are pancreatic pseudocysts and its histology

Answer 15

Associated with acute and chronic pancreatitis → pseudocyts → resolution, perforation, compression of adjacent structures, infection

Lined by fibrous tissue (no epithelial lining)
Contains fluid (rich in pancreatic enzymes or necrotic material)
Connects with pancreatic ducts

Question 16

What is IgG4 related disease of the pancreas

Answer 16

Autoimmune pancreatitis
Large numbers of IgG4 +ve plasma cells
May involve the pancreas, bile ducts and almost any other part of the body

Duct is surrounded by loads of IgG4 expressing plasma cells
These patients respond very well to steroids

Question 17

What are the tumours of the pancreas

Answer 17

Carcinoma (85%):
- Ductal (5% of deaths)
- Acinar → Acinar-ductal metaplasia
Cystic neoplasms
- Serous cystadenoma
- Mucinous cystic neoplasm
Pancreatic neuroendocrine tumours (islet cell tumours)

Question 18

What are the risk factors for pancreatic cancer

Answer 18

Smoking
BMI and dietary factors
Chronic pancreatitis
Diabetes mellitus

Question 19

Describe ductal carcinomas of the pancreas (epidemiology, aetiology, prognosis)

Answer 19

Increasingly common with age; M>F (2: 1)
Pre-malignant bridges that do NOT invade through the BM:
- Pancreatic intraductal neoplasia (PanIN)
- Intraductal Mucinous papillary neoplasm
95% k-ras mutation
5-year survival = 5%

Question 20

Describe the histology of pancreatic ductal carcinomas

Answer 20

Macroscopic:
- Gritty and grey
- Invasion of adjacent structures
- Head (60%), body, tail, diffuse

Microscopic:
- Adenocarcinomas: mucin secretion, gland formation, desmoplastic stroma (tumour induces fibrous tissue growth around it)
- Perineural invasion

Question 21

How do ductal carcinomas of the pancreas spread

Answer 21

DIRECT: bile ducts, duodenum
LYMPHATIC: lymph nodes
BLOOD: liver
SEROSA: peritoneum

Question 22

What are the complications of ductal carcinoma of the pancreas

Answer 22

Due to spread
Chronic pancreatitis
Venous thrombosis (migratory thrombophlebitis) – CHARACTERISTIC →Circulating pancreatic cancer cells releasing mucous which activates the clotting cascade

Question 23

Describe acinar pancreas carcinomas

Answer 23

Acinar-ductal metaplasia - most tumours arise from the acini but appear to arise from the ducts due to acinar-ductal metaplasia
Histology: neoplastic epithelial cells with eosinophilic granular cytoplasm. Positive immunoreactivity for lipase, trypsin and chymotrypsin.
Associated with increased serum lipase → multifocal fat necrosis and polyarthralgia

Question 24

Describe cystic tumours of the pancreas

Answer 24

Includes serous cystadenomas and mucinous cystic neoplasm
Contain serous or mucin secreting epithelium (like ovarian tumours)
Usually benign

Question 25

Describe pancreatic endocrine neoplasms

Answer 25

Usually non-secretory
Stained by neuroendocrine markers (Chromogranin)
Includes:
- Insulinomas (beta cell)
- MEN1
tail > body > head

Question 26

What is Whipple’s triad

Answer 26

Hypoglycaemia
S/S hypoglycaeima
Relief of symptom of administration of glucose

Question 27

What are the risk factors for gallstones

Answer 27

Female
40yo
Obesity
Ethnicity (e.g. Native Americans) - 20% of the West have gallstones
Hereditary factors (e.g. disorders of bile metabolism)
Drugs (e.g. oral contraceptive)
Acquired disorders (e.g. rapid weight loss)

Question 28

What are the types of gallstone and what is their appearance on AXR

Answer 28

Cholesterol (>50%): single stone, radio-lucent on AXR (US to diagnose)
Pigment (calcium salts of unconjugated bilirubin): multiple, radio-opaque (contains Ca)

Question 29

What are the complications of gallstones

Answer 29

Bile duct obstruction
Acute and chronic cholecystitis
Gallbladder cancer
Pancreatitis

Question 30

What is the histology of acute cholecystitis

Answer 30

Acute inflammation (neutrophils, oedema)
90% are associated with gallstones

Question 31

What is the histology of chronic cholecystitis

Answer 31

90% contain gallstones
Fibrosis, small, neoangiogenesis
Diverticula (Rokitansky-Aschoff sinuses) – gallbladder contracting against obstruction → diverticula

Question 32

Describe pancreatic action

Answer 32

Secretin and CCK → 2L a day of enzymic HCO3- rich fluid

Secretin = gastric-acid secretion and buffering with HCO3-, produced by s-cells of duodenum
CCK = stimulates digestion of fat and protein, produced by i-cells in the duodenum

Question 33

What are the functions of the pancreas

Answer 33

Exocrine: digestion (protease, lipase, amylase release)
Endocrine: secretion of hormones
- Alpha: glucagon
- Beta: insulin
- Delta: somatostatin (regulation of alpha and beta)
- D1: vasoactive peptide → stimulates H2O secretion
- PP: pancreatic polypeptide, self-regulates secretion activities

Question 33

What is metabolic syndrome

Answer 33

Collection of conditions that increase risk of IHD
- Fasting hyperglycaemia >6 mmol/l.
- BP >140/90
- Central obesity (>94cm in M, >80cm F)
- Dyslipidemia: Decreased HDL cholesterol <1mmol/l & Increased TGs >2mmol/l
- Microalbuminaemia

Question 34

How is pancreatitis severity scored

Answer 34

GLASGOW
≥3 = Severe Pancreatitis

Question 35

What is the difference between cholecystitis, cholelithiasis, and cholangiocarcinoma

Answer 35

Cholecystitis = Inflammation of the gall bladder (chronic → inflammation → fibrosis)
Cholelithiasis = Presence of the gallstones in the gall bladder
Cholangiocarcinoma = adenocarcinoma of the gall bladder

Question 36

What are the types of multiple endocrine neoplasia (MEN)

Answer 36

MEN1:
- Parathyroid hyperplasia/adenoma
- Pancreatic endocrine tumour (often phaeochromocytoma)
- Pituitary adenoma
MEN 2A
- Parathyroid
- Thyroid
- Phaeochromocytoma
MEN 2B
- Medullary Thyroid
- Phaeochromocytoma
- Acoustic Neuroma
- Marfanoid phenotype

Question 37

What are the pancreatic malformations

Answer 37

Ectopic Pancreas – esp. stomach, small intestine.
Pancreas Divisum – failure of fusion of dorsal and ventral buds, increased risk of pancreatitis.
Annular pancreas – can present with duodenal obstruction approx. 1yo

Question 38

What are the symptoms and signs of pancreatic ductal adenocarcinoma

Answer 38

Weight loss (cachexia) and anorexia
Upper abdominal and back pain (chronic, persistent and sever)
Jaundice (painless), pruritus, steatorrhoea
DM
Trousseau’s syndrome (25%)- recurrent superficial thrombophlebitis
Ascites
Abdominal mass
Virchow’s node
Courvoisier’s sign

Question 39

What investigations should be done for ductal adenocarcinoma of the pancreas and what is the management

Answer 39

Bloods: ↓Hb, ↑Bili, ↑Ca2+
CT/MRI/ERCP
CA19.9 >70IU/mL

Mx: Palliative chemo, Whipple’s procedure