Pathology of the Pancreas

Question 1

What is an annular pancreas?

Answer 1

developmental malformation in which the pancreas forms a ring around the duodenum (risk of duodenal obstruction).

Question 2

What is ACUTE pancreatitis?

Answer 2

inflammation and hemorrhage of the pancreas due to autodigestion of pancreatic parenchyma by pancreatic enzymes (from premature activation of TRYPSIN leading to activation of other pancreatic enzymes).

Question 3

What type of necrosis does ACUTE pancreatitis cause?

Answer 3

liquefactive hemorrhage (coagulative) necrosis of the pancreas and fat necrosis of the peripancreatic fat.

Question 4

What are the 2 most common causes of ACUTE pancreatitis?

Answer 4

ALCOHOL and GALLSTONES (both of which block the sphincter of Odi, either by a stone or increased contraction of the sphincter).

Question 5

What are some other causes of ACUTE pancreatitis?

Answer 5

• trauma (especially automobile accidents involving children due to the seat belt compressing the abdomen instead of the waist causing ischemic injury).
• hypercalcemia (calcium is an activator of enzymes).
• hyperlipidemia
• drugs (furosemide, estrogens)
• scorpion stings
• mumps
• and rupture of a posterior duodenal ulcer (because the head of the pancreas sits slightly posterior to the duodenum).
• inherited mutations in genes encodign trypsinogen (PRSS1) and trypsin inhibitor (SPINK1).

Question 6

What are the clinical features of ACUTE pancreatitis?

Answer 6

• epigastric abdominal pain that radiates to the back.
• nausea and vomiting.
• periumbilical and flank hemorrhage (necrosis spreads into the periumbilical soft tissue and retroperitoneum).
• elevated serum lipase and amylase (lipase is more specific).
• hypocalcemia (calcium is consumed during saponification in fat necrosis).

Question 7

What are the 4 complications of ACUTE pancreatitis?

Answer 7

1. shock (due to peripancreatic hemorrhage and fluid sequestation).
2. pancreatic pseudocyst (formed by fibrous tissue surrounding liquefactive necrosis and pancreatic enzymes; lack epithelial lining. This presents as an abdominal mass with elevated amylase and rupture is assoicated with release of enzymes into the abdominal cavity).
3. pancreatic abscess (often due to E. coli, presents with abdominal pain, high fever, and persistently elevated amylase).
4. DIC (due to enzymes destroying Co-A factoras in the blood) and ARDS (from enzymes destroying capillary-alveolar interface).

Question 8

What defines CHRONIC pancreatitis?

Answer 8

• fibrosis of pancreatic parenchyma from chemokines, TGF-B and PDGF stimulating production of myofibroblasts (most often secondary to recurrent acute pancreatitis) from alcohol (adults) and cystic fibrosis (children; CFTR gene mutation= decreased pancreatic bicarb secretion leading to protein plugging).
• may see damage to ENDOCRINE pancreas as well.

Question 9

What are the clinical features of CHRONIC pancreatitis?

Answer 9

• epigastric abdominal pain that radiates to the back in addition to pancreatic insufficiency (results in malabsorption with steatorrhea and fat soluble vitamin deficiencies; A, D, E, and K).
• dystrophic calcification of pancreatic parenchyma on imaging (chain of lakes pattern due to dilation of pancreatic ducts).
• secondary DM (rare but can occur as a late complication due to destruction of islets).
• increased risk for pancreatic carcinoma

Question 10

Are amylase and lipase useful serologic markers of chronic pancreatitis?

Answer 10

NO (only acute).

Question 11

What is pancreatic carcinoma?

Answer 11

• adenocarcinoma arising from the pancreatic DUCTS, most commonly seen in the elderly.
• most tumors arise in the head of the pancreas, are usually hard stellate, gray-white and poorly defined.

Question 12

What are the 2 major risk factors for pancreatic carcinoma?

Answer 12

1. smoking

2. chronic pancreatitis

Question 13

What are the clinical features (usually occur late in disease) of pancreatic carcinoma?

Answer 13

• epigastric abdominal pain and weight loss.
• obstructive jaundice (due to leaking of conjugated bilirubin into the blood) with pale stool and palpable gallbladder (from tumors in head of pancreas).
• secondary DM (from tumors in the body or tail).
• pancreatitis
• migratory thrombophlebitis (TROUSSEAU syndrome)= presents as swelling, erythema, and tenderness in the extremities (10% of patients).
• serum tumor marker is CA 19-9.

Question 14

How do you treat pancreatic carcinoma?

Answer 14

surgical resection of the head and neck of pancreas, proximal duodenum, and gallbladder (WHIPPLE PROCEDURE).

Question 15

What is the prognosis for pancreatic carcinoma?

Answer 15

very bad (1-year survival is

Question 16

How is trypsin related to the clotting and complement systems?

Answer 16

trypsin converts prekalikrein to its activated form, initiating the actions of the kinin system and activating Hageman factor (factor XII) for clotting.

Question 17

What are some ways that pancreatic enzymes become inappropriately activated in acute pancreatitis?

Answer 17

1. pancreatic duct obstruction= increase in ductal pressure causing enzyme rich fluid to accumulate in the interstitium.
2. primary acinar cell injury= mumps, trauma, shock, ischemia.
3. defective intracellular transport of proenzymes within acinar cells.

Question 18

What inappropriate pancreatic enzyme is responsible for hemorrhage?

Answer 18

elastase

Question 19

What is lymphoplasmacytic sclerosing pancreatitis?

Answer 19

autoimmune form with duct centric mixed inflammatory infiltrate, venulitis and increased number of plasma cells.
*clinically mimics pancreatic cancer, but can be treated with steroids.

Question 20

What are pancreatic congenital cysts?

Answer 20

• thin, fibrous capsule lined by a single layer of cuboidal epithelium containing serous fluid that arises from anomalous development of the pancreatic ducts.

Question 21

With what may congenital cysts be seen?

Answer 21

polycystic ovarian syndrome and von Hippel-Lindau disease

Question 22

What are serous cystadenomas of the pancreas?

Answer 22

BENIGN small cysts surrounded by glycogen rich cells.

• cysts contain clear, straw-colored fluid
• more common in women

Question 23

What are mucinous cystic neoplasms?

Answer 23

• cysts surrounded by columnar epithelium and filled with thick serous fluid.
• arise in the body or tail of pancreas and can be associated with invasive cancer.
• painless and slow growing
• most in women
• larger than cystadenomas
• KNOW PICTURE

Question 24

What are intraductal papillary mucinous neoplasms?

Answer 24

• mucin secreting intraductal neoplasms that are more common in men.
• involve the head of the pancreas more often
• lacks dense stroma
• benign or malignant (remember invasion is a sign of malignancy).
• KNOW PICTURES

Question 25

What is a solid-pseudopapillary neoplasm?

Answer 25

• unusual, well circumscribed masses that have both solid and cystic components to them.
• seen in young women
• have mutations of beta catenin.

Question 26

What is important about pancreatic intraepithelial neoplasias (PaINs)?

Answer 26

they are often found adjacent to infiltrating cancer (stratification of nuclei, hyperchromasia, high N/C ratio)…

Question 27

What is the most frequently altered gene in pancreatic cancer?

Answer 27

K-RAS gene (remember RAS activates intracellular signal transduction pathways therefore activating transcription factors).

Question 28

What gene is often inactivated in pancreatic cancer?

Answer 28

• CDKN2A(16)= tumor suppressor gene

- p53= tumor suppressor gene that acts as a cell cycle checkpoint and can induce apoptosis.

Question 29

Where does metastasis of pancreatic carcinoma normally occur?

Answer 29

liver, lungs, and bones

Question 30

What is acinar cell carcinoma?

Answer 30

prominent acinar cell differentiation with formation of zymogen granules and production of TRYPSIN and LIPASE.
*SEE PICTURES

Question 31

What is pancreatoblastoma?

Answer 31

rare malignant tumors seen in children that are SQUAMOUS ISLANDS mixed with acinar cells