Liver Path 7: Pancreas

Question 1

Exocrine pancreas

Answer 1

constitutes 80% to 85% of the organ composed of acinar cells that secrete enzymes needed for digestion. (~1.5L of secretions)

Question 2

Endocrine pancreas

Answer 2

is composed of about 1 million clusters of cells, the islets of Langerhans. Islet cells secrete insulin, glucagon and somatostatin and constitute only 1% to 2% of the organ.

Question 3

Congenital Anomalies of Pancreas

Answer 3

Pancreas divisum most common anomaly (2 ducts)

Annular pancreas can be associated with duodenal obstruction (wraps around the duodenum)

Ectopic pancreas

Agenesis (very rare)

Question 4

complications of head of the pancreas tumors?

Answer 4

cholestasis (common bile duct obstruction)

Question 5

Acute Pancreatitis

Answer 5

Autodigestion of the pancreas by its own enzymes *(inappropriate activation of digestive proenzymes) initiated by:

• Alcohol (65% in US)
• Pancreatic duct obstruction (calculi) (20%)
• Drugs (furosemide, associated with HIV treatment)
• Vascular injury (ischemia)
• Infections (viruses including mumps)
• Hereditary factors (Hereditary pancreatitis)
• Hypercalcemia

Mortality rate averages 10%,

Question 6

prognosis - acute pancreatitis

Answer 6

Most attacks of acute pancreatitis do not lead to complications, and most people recover uneventfully with medical care.

A small proportion of people have a more serious illness that requires intensive medical care.

Question 7

A complex combination of genetic, environmental, and metabolic factors contribute to the development and recurrence of acute and chronic pancreatitis

Answer 7

Multiple lines of evidence indicate that premature activation of trypsin in acinar cells damages the cells causing inflammatory response recognize clinically as acute pancreatitis

Many different genetic factors affect acinar cell function, bile duct function, trypsin inactivation and intensity of a immune response in the pancreas

Question 8

Acute Pancreatitis - clinical

Answer 8

Peak age range for initial episode is 35 to 44 yrs

Diagnosing acute pancreatitis can be difficult because the signs and symptoms of pancreatitis are similar to other medical conditions

Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. (Moderate sensitivity, high specificity)

Serum lipase rises within 4 to 8 hours of onset of acute pancreatitis (high sensitivity and specificity)

Question 9

Acute Pancreatitis Histopathology

Answer 9

Acute interstitial pancreatitis
Interstitial edema, and focal areas of fat necrosis in peri-pancreatic fat

Acute necrotizing pancreatitis
Necrosis of acinar and ductal tissues as well as islets of Langerhans

Hemorrhagic pancreatitis
Extensive parenchymal necrosis accompanied by dramatic hemorrhage within the pancreas

Question 10

Chronic Pancreatitis

Answer 10

Can be initiated by recurrent acute pancreatitis  myofibroblast stellate cell activation

Irreversible destruction of exocrine parenchyma with fibrosis –> destruction of endocrine parenchyma –> insulin-dependent diabetes

Loss of exocrine function is clinically apparent with loss of ~85-90% of the exocrine gland

Question 11

Causes of Chronic Pancreatitis

Answer 11

Alcohol abuse 70-80% of cases

Repeat episodes of acute pancreatitis
(10-20%)

Obstruction of the pancreatic duct by calculi or neoplasms

Metabolic

• Primary hyperparathyroidism
• Hyperlipidemia
• Renal transplantation
• Cystic fibrosis

Question 12

Chronic Pancreatitis Diagnosis

Answer 12

Histology remains the gold standard for the diagnosis of chronic pancreatitis

Demonstrating a reduction in bicarbonate in a duodenal aspirate after secretin stimulation

Endoscopic retrograde cholangiopancreatography (ERCP) shows abnormal pancreatic ductal system

Presence of chunky intrapancreatic calcifications on plain radiographs (minority of cases)

Question 13

Autoimmune Pancreatitis Variant

Answer 13

Unique Mass forming inflammatory form of chronic pancreatitis

Elevated IgG4

Radiographic findings Mimic pancreatic adenocarcinoma

Approximately 25% of pancreatic resections that lack evidence of malignancy may represent AIP

20% associated with other autoimmune disorders

Responds to corticosteroid therapy

Question 14

Pancreatic Pseudocyst Non-neoplastic

Answer 14

Most common pancreatic cyst (75%)

Associated with pancreatitis, acute or chronic

Usually do not need to be treated

Can be associated with infection, bleeding or rupture

Question 15

Pancreatic Cystic Neoplasms: Serous cystadenoma

Answer 15

Most common cystic neoplasm of pancreas
Most are benign
Average age 66 years, female to male 2:1
Lined by a single layer of flat to cuboidal cells with clear cytoplasm

Each small cyst is lined by a flattened layer of epithelium. Cytologically, the lining cells have small, uniform, hyperchromatic nuclei.

Question 16

Pancreatic cystic neoplasms: Mucinous cystadenoma

Answer 16

Average age 50 years, >95% in females
Can be precursors to invasive carcinoma
Almost always in the tail of the pancreas
Lining epithelium consists of tall columnar cells with abundant apical mucin

Cystic spaces lined by tall columnar mucin containing cells

Question 17

Intraductal Papillary Mucinous Neoplasm (IPMN)

Answer 17

Involve * larger ducts of pancreas usually in the head of the pancreas

• Male > Female

Benign, borderline & malignant * (Invasive carcinoma is identified in one third of cases)

Mucinous cells with various degrees of dysplasia and papillary architecture line cystically dilated ducts of these tumors

Question 18

Invasive Ductal Carcinoma of Pancreas

Answer 18

Most common type of pancreatic neoplasm, 60% in head of pancreas

Overall 5 year survival rate is less than 5% with median survival of 9 months

Patients often present with jaundice or back pain with weight loss

Most are sporadic with approximately 10% familial

10% associated with migratory thrombophlebitis (Trousseau sign) secondary to release of platelet activating factors and procoagulant factors

Question 19

Armand Trousseau 1801-1867

Answer 19

French internist
coined the terms aphasia
and forme fruste

Migratory thrombophlebitis
Trousseau sign led him to diagnose his own pancreatic cancer

Question 20

Pathology of Ductal Adenocarcinoma of Pancreas

Answer 20

Invasive pancreatic cancers appear to arise from pancreatic intraepithelial neoplasia (PanIN)

Tendency to invade peri-pancreatic tissues and elicit desmoplastic tissue reaction

KRAS is the most frequently altered oncogene

Most are moderate to poorly differentiated adenocarcinoma

Question 21

Primary effects of invasive ductal carcinoma of pancreas

Answer 21

Metastases- lung, liver, peritoneum

abdominal pain (perineural lymphatic invasion)

Question 22

secondary effects of invasive ductal carcinoma of pancreas

Answer 22

weight loss
obstructive jaundice
courvoisier gallbladder
migratory thrombophlebitis

Question 23

Acinar Cell Carcinoma of Pancreas

Answer 23

Uncommon accounting for less than 2% of pancreatic cancers

Most patients are adults >60 years of age

15% develop lipase hypersecretion syndrome

Metastasizes early

Poor prognosis slightly better than invasive ductal carcinoma of pancreas

Question 24

Pancreatoblastoma

Answer 24

Uncommon, but the most frequent type of pancreatic tumor seen in early childhood

Mean patient age at diagnosis of 4 years

Epithelial tumor that exhibits acinar differentiation and often a lesser degree of neuroendocrine and ductal differentiation

In childhood, most cases that are detected before the occurrence of metastases are curable by surgery.

Question 25

Pancreatic Neuroendocrine Tumor-PanNET

Answer 25

Approximately 5% to 8% of clinically relevant pancreatic tumors

May occur at any age but are more common in adults (mean age at diagnosis, 55 to 60 years).

Most produce some peptide hormone but most are non-functional (no symptoms)

Preferentially metastasize to regional lymph nodes and liver