Pancreatic pathology Flashcards by Grace Hopkinson

pancreas is located in the

deep retroperineum

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which part of the pancreas is dissected during surgery

the neck

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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

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Functions of the pancreas:

ENDOCRINE

Islets of Langerhans
Secrete peptide hormones into blood e.g. insulin and glucagon

1-2% of the pancreas

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What is pancreatitis?

Inflammation of the pancreas

Caused by injury to the exocrine parenchyma

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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

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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

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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

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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

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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.

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Mild pancreatitis presents as

Swollen gland with fat necrosis

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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).

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Complications of pancreatitis

Shock
Intravascular coagulopathy
Haemorrhage
Pseudocysts (collections of pancreatic juice secondary to duct ruptutre)

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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

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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

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Clinical presentation of chronic pancreatitis

Intermittent abdo pain, back pain and weight loss

Fibrosis of exocrine tissue – can mimic carcinoma macroscopically and microscopically

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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

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Pathogenesis of chronic pancreatitis

Ductal obstruction by concretions (protein plugs)

Direct toxic effects – e.g. alcohol

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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

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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

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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) 1. K-ras mutations 2. P60 mutations 3. 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.