Pancreatic pathology Flashcards
pancreas is located in the
deep retroperineum
which part of the pancreas is dissected during surgery
the neck
Functions of the pancreas: EXOCRINE
exocrine is 85% of pancreas
glands secrete chemicals into the ducts that then reach the duodenum
Trypsin, lipase and amylase secreted.
Conversion of trypsinogen to trypsin occurs at the duodenum
Functions of the pancreas:
ENDOCRINE
Islets of Langerhans
Secrete peptide hormones into blood e.g. insulin and glucagon
1-2% of the pancreas
What is pancreatitis?
Inflammation of the pancreas
Caused by injury to the exocrine parenchyma
What is the difference between acute and chronic pancreatitis?
Acute - the gland reverts to normal if underlying cause is removed
Chronic - irreversible loss of the pancreatic tissue
Aetiology of acute pancreatitis
50% of cases are caused by gallstones
25% of cases are caused by alcohol
Rare causes include:
- vascular insufficiency
- viral infections like mumps
- hypercalcaemia
- ERCP
- Inherited causes
Hereditary pancreatitis - what is it?
Recurrent attacks of severe pancreatitis
Usually beginning in childhood
Caused by mutations of:
PRSS1 - Aut. dominant
SPINK 1 gene - Aut. recessive
Clinical features of acute pancreatitis
Emergency requiring admission to hospital
Sudden onset of severe abdomen pain
Nausea & vomiting
Raised serum amylase/lipase with persistent hypocalcaemia
Pathogenesis of acute pancreatitis (if caused by obstruction e.g. gallstones)
Damages duct lining.
Leakage and activation of pancreatic enzymes. e.g. Amylase released into blood.
Mild pancreatitis presents as
Swollen gland with fat necrosis
Severe acute pancreatitis presents as
swollen, necrotic gland with fat necrosis and haemorrhage (Grey Turner’s sign)
Haemorrhage into the subcutaneous tissues of flank.
(Cullen’s sign – periumbilicus).
Complications of pancreatitis
- Shock
- Intravascular coagulopathy
- Haemorrhage
- Pseudocysts (collections of pancreatic juice secondary to duct ruptutre)
Chronic pancreatitis - what is it and what can it lead to?
Progressive inflammatory disorder
parenchyma of pancreas is destroyed and replaced by fibrous tissue.
Irreversible destruction of the exocrine tissue, followed by destruction of the endocrine tissue
Leads to malnutrition and diabetes
The relationship between acute and chronic pancreatitis
Not two distinct diseases but a continuum:
Recurrent acute can develop chronic pancreatitis
Both genetic and environmental factors:
Experimental protocols can be modified to induce each condition
Clinical presentation of chronic pancreatitis
Intermittent abdo pain, back pain and weight loss
Fibrosis of exocrine tissue – can mimic carcinoma macroscopically and microscopically
Chronic Pancreatitis Aetiology
Toxic –alcohol, cigarette smoke, drugs, hypercalcaemia, hyperparatyroidism infections
Idiopathic
Genetic CFTR (cystic fibrosis gene), PRSS1, SPINK- 1 mutations
Autoimmune
Recurrent acute pancreatitis
Obstruction of main duct – cancer, scarring
Pathogenesis of chronic pancreatitis
Ductal obstruction by concretions (protein plugs)
Direct toxic effects – e.g. alcohol
What are the physiological effects of chronic pancreatitis?
Localised, irregular involvement of the gland early on, later global atrophy.
Dilated and distorted ducts
Calculi, esp in alcohol induced cases.
Fatty replacement. Fibrosis
Pseudocyst formation
What are the complications of chronic pancreatitis?
Malabsorption of fat (lack of lipases)
Steatorrhoea
Impairment of fat soluble vitamin absorption –A,D, E and K
Diarrhoea, weight loss and cachexia
Diabetes (late feature)
Pseudocysts
Stenosis of common bile duct/duodenum
Severe chronic pain
Mortality rates of chronic pancreatitis
Mortality rate - nearly 50% with 20-25 years of disease onset
Pancreatic ductal adenocarcinoma - how common is it and what is it’s mortality rate?
Most common type of pancreatic ductal adenocarcinoma
10th most common cancer in the UK
5 year survival prediction is really low (4%)
Rare to have onset before 40 years of age
More common in men
Epidemiology of Pancreatic ductal adenocarcinoma - what are the risk factors?
Complex and multifactorial:
Cigarette smoking (20% of cases, and increases risk by 2-3x)
Family history 10% cases
Nutritional and dietary factors diet rich in red meats, obesity, low physical activity, low intake of fruit and veg
Other conditions chronic pancreatitis, diabetes mellitus
Alcohol
What is the difference between familial and hereditary pancreatic cancer?
Familial:
Pancreatic cancer in 2 or more first degree relatives that is often caused by an absence of known germline mutation
Familial cancers occur at younger age and more common in certain groups.
Hereditary:
Due to an unidentified causative underlying germline mutation
Hereditary cancer syndromes associated with pancreatic cancers (5-10% of cases)
Lynch syndrome (caused by DNA mismatch repair)
FAMMM - multiple melanoma syndrome
Breast and ovarian cancer (BRCA2, BRACA1)
Peutz-Jeghers - LKB1/STK11
Progression model for adenocarcinoma of the pancreas (3 steps)
PanIN progression (pancreatic intraepithelial neoplasia)
- K-ras mutations
- P60 mutations
- Inactivation of BRCA 2 and p53
Where in the pancreas does pancreatic carcinoma occur?
60-70% the head
5-15% the body
10-15% tail
How does a pancreatic carcinoma appear?
Grossly: is hard, yellow-white, poorly defined mass.
Occasional micro and macrocystic areas
Are pancreatic carcinomas invasive?
They are highly invasive
Produce a desmoplastic response
Cancers in the pancreatic head
Appear as a double duct sign: stenosis and proximal dilation of the common bowel duct and the pancreatic duct
Present with jaundice due to high bilirubin
Most infiltrate to surrounding tissues e.g. mesenteric vessels
Cancers of the pancreatic body or tail
can infiltrate into the stomach, left side of colon, spleen and adrenal gland
Why is pancreatic cancer so hard to treat in terms of presentation?
It is present for at least a decade before it’s detected - early cancer is silent
There are non specific symptoms e.g. epigastric pain that radiates to the back
Clinical features of more advanced pancreatic carcinoma
Weight loss Painless jaundice Pruritis (itchiness) Nausea Trousseau's syndrome Courvoisier's sign Distant metastases Diabetes
What is Trousseau’s syndrome?
Migratory thromophlebitis
What is Courvoisier’s sign?
Palpable gallbladder
What is the survival rate of pancreatic carcinoma?
Almost universally fatal
Mean survival if untreated is 3-5 months
If treated, the individual may survive 10-20 months
What are the poor prognostic factors of pancreatic adenocarcinoma?
- Extension of tumour outside pancreas
- Metastatic spread to local lymph nodes
- Vascular and perineural invasion
- Poor differentiation
- Positive margins on resection
What are pancreatic neuroendocrine tumours?
Uncommon pancreatic neoplasms (< 3%)
Derived from islet cells
What is the epidemiology of pancreatic neuroendocrine tumours?
20-60 years of age
M=F
Incidence is <1 per 100,000 per year
Recent increasing incidence
Risk factors of pancreatic neuroendocrine tumours
- Smoking
- Family history
- alcohol
- obesity
- diabetes
Increased risk MEN 1, NF-1 and VHL
Neuroendocrine tumours
Well differentiated Mild to moderate cellular atypia No necrosis Slow growing Often functioning
Neuroendocrine carcinomas
Poorly differentiated Highly atypical Necrosis Fast growing Lower survival rate
What is an Insulinoma?
Functioning pancreatic neuroendocrine neoplasm
Derived from beta cell
Clinical findings: hypoglycaemia
What is a glucagonoma?
Functioning pancreatic neuroendocrine neoplasm
Derived from alpha cell
Clinical findings: Stomatitis Rash Diabetes Weight loss
What is a gastrinoma?
Functioning pancreatic neuroendocrine neoplasm
G cell derived
Causes Zollinger Ellison syndrome
Clinical findings:
Peptic ulcer and diarrhoea
What is a somatostatinoma?
Functioning pancreatic neuroendocrine neoplasm S cell Causes somatostatinoma syndrome Clinical findings: Diabetes Cholelithiasis Hypochlorhydria
What is VIPoma
Functioning pancreatic neuroendocrine neoplasm that causes Verner-Morrison syndrome.
Clinically:
diarrhoea
hypokalaemia
achlorydria
What is pp-cell PEN?
PP cell derived functioning pancreatic neuroendocrine neoplasm
How do neuroendocrine tumours appear upon excision?
Well circumscribed
Solid
10-50mm
Occur anywhere in the pancreas and can be multiple of them
The risk of progression in pancreatic neuroendocrine tumours
Risk of tumour progression is hard to predict
Often requires long follow ups
Mets can occur many years after primary tumour
Regional lymph nodes and liver are common sites for mets.
