Pancreas

Question 1

Pancreatic Agenesis

Answer 1

• absence of pancreas, associated with severe malformations.
• not compatible with life.

Question 2

Pancreas Divisum

Answer 2

• most common pancreatic congenital abnormality (3-10% incidence).
• failure of ventral and dorsal ftal duct systems to fuse ⇒ most pancreatic secretions drain through minor papilla.
• predisposes to chronic pancreatitis.

Question 3

Annular Pancreas

Answer 3

• bandlike ring of normal pancreatic tissue encircles second portion of duodenum.
• can cause duodenal obstruction.

Question 4

Ectopic Pancreas

Answer 4

• 2% incidence.
• can be found in stomach, duodenum, jejunum, Meckel diverticulum, ileum.
• submucosal, single or multiple, a few mm - cm.
• can cause inflammation, pain, and rarely bleeding.

Question 5

Acute Pancreatitis

Answer 5

• reversible parenchymal damage associated with inflammation.
• 80% with biliary tract disease (gallstones) or alcoholism.
• 10-20% idiopathic.
• hereditary = recurrent bouts of pancreatitis starting as kid. autosomal dominant mutation in **PRSS1 **⇒ activated trypsin resistant to self-inactivation.
  
  • can have autosomal recessive mutation in serine protease inhibitor Kazal type 1 gene (SPINK1). fials to inhibit trypsin activity.
• morphology: mild interstitial edema and inflammation to extensive necrosis and hemorrhage.
  
  • vascular leakage ⇒ edema; necrosis of regional fat by lipolytic enzymes; acute inflammation; proteolytic destruction of pancreas; vascular injury with hemorrhage.
  • mild = edema, fat necrosis, acute inflammation.
  • acute necrotizing pancreatitis = gray-white parenchymal necrosis and chalky white fat necrosis.
  • acute hemorrhagic = patchy red-black hemorrhage with fat necrosis.
• pathogenesis: from parenchymal autodigestion from pancreatic enzymes (inappropriate inactivation of trypsinogen).
  
  • trypsin activated in pancreas allows proenzymes to be activated and prekallikrein to kallikrein which activates kinin system and clotting.
  • causes inflammation and thrombosis with proteolysis, lipolysis, and hemorrhage.
  • pancreatic duct obstruction = gallstones or sludge in apmulla. lipase ⇒ fat necrosis. inflammation and edema compromises vascular flow, causes ischemia.
  • primary acinar cell injury = from viruses (mumps), drugs, trauma, or ischemia.
  • defective intracellular transport of proenzymes = misdirected toward lysosomes. hydrolyzes proenzymes and releases.
  • alcohol = toxic to pancreatic acinar cells. causes functional obstruction by contracting spincter at ampulla and ↑ pancreatic protein secretion ⇒ inspissated protein plugs.
• presentation: abd pain, nausea, anorexia, ↑ plasma levels amylase and lipase.
  
  • full blown = medical emergency with intense abd pain, peripheral vascular collapse, shock. death in 5% from shock, ARDS, or acute renal failure.
  • labs: ↑ serum amylase, glycosuria, hypocalcemia from fat necrosis.
  • necrotic debris can become infected.
• tx: restricting oral intake, analgesia, nutrition, volume support.
• complications: pancratic abscesses, pancreatic pseudocysts.

Question 6

Chronic Pancreatitis

Answer 6

• inflammation with irreversible parenchymal destruction and fibrosis.
• long-term alcohol abuse common.
• also from ductal obstruction from pseudocysts, tumors, orcalculi, pancreas divisum, hereditary pancreatitis, CFTR mutations (⇒ ↓ ductal cell bicar secretion, promotes plugging).
• pathogenesis: from ductal obstruction by concretion, toxic effects (alcohol and metabolites), oxidative stress.
• morphology: replacement of pancreatic acinar tissue by dense fibrous CT, relative sparing of islets of Langerhans, variable dilation of pancreatic ducts. pancreas hard with focal calcifications.
  
  • lymphoplasmacytic sclerosing pancreatitis = autoimmune pancreatitis. have mixed inflammatory cell infiltrates, venulitis, IgG₄-producing plasma cells. responds to steroids.
• presentation: can be silent or recurrent pain and/or jaundice. precipitated by alcohol abuse, overeating, opiates.
  
  • late complications = malabsorption, diabetes mellitus, pseudocysts.
  • 50% mortality within 20-25 yrs.

Question 7

Congenital Pancreatic Cysts

Answer 7

• from anomalous development of pancreatic ducts.
• congenital polycystic disease = coexist in kidney and liver.
• von Hippel-Lindau disease = see pancreatic cysts and angiomas of CNS.
• unilocular, thin-walled, cuboidal epithelial lining.

Question 8

Pancreatic Pseudocysts

Answer 8

• collections of necrotic-hemorrhagic material rich in pancreatic enzymes. from walled off areas of fat necrosis.
• are 75% of pancreatic cysts.
• encircled by fibrosed granulation tissue.
• from bouts of acute pancreatitis or trauma.
• spontaneously resolve or get infected or compress adjacent structures.

Question 9

Serous Cystadenoma

Answer 9

• painless, slow growing mass.
• women >60yrs.
• solitary, well circumscribed nodules with central stellate scar.
• made of numerous 1-3mm cysts lined by glycogen-rich cuboidal epithelium with serous watery fluid.
• benign and cured by resection.

Question 10

Mucinous Cystic Neoplasm

Answer 10

• painless slow growing mass.
• multiloculated cystic neoplasms, filled with thick mucinous material. lined by mucin-producing columnar cells within dense stroma.
• 95% in women, masses in body or tail of gland.
• 1/3 lesions have invasive adenocarcinoma.

Question 11

Intraductal Papillary Mucinous Neoplasm (IPMN)

Answer 11

• more common in men. arise in head of gland.
• 10-20% multifocal. lack dense stroma, involve a larger pancreatic duct, have malignant potential.

Question 12

Solid-Pseudopapillary Tumor

Answer 12

• round, well circumscribed neoplasm. have solid and cystic regions.
• mainly in young women. cause abd discomfort from large size.
• associated with activating mutation of beta-catenin.
• locally aggressive but cured by resection.

Question 13

Pancreatic Carcinoma

Answer 13

• an infiltrative ductal adenocarcinoma. 4th leading cause of cancer death is US.
• progress from non-neoplastic epithelium to small ductal non-invasive lesion to invasive carcinoma.
  
  • precursor lesion = pancreatic intraepithelial neoplasms (PanINs). have genetic and epigenetic alterations with short telomeres.
• KRAS = most altered gene (90%) ⇒ active protein, ↑ Fos and Jun transcription factor activation.
• CDKN2A (p16) = inactivated in 95%
• SMAD4 = tumor suppressor gene, inactivated in 50%. encodes TGF-beta receptor signal transdution.
• p53 = inactivation means no apoptosis or cell senescence.
• pathogenesis: 80% btw ages 60-80yrs. smoking increases risk 2x. risk from chronic pancreatitis, fat rich diets, family history of pancreatic cancer, diabetes mellitus.
• morphology: 60% in head of gland, 15% in body, 5% in tail, 20% diffuse.
  
  • highly invasive, intense host scarring response (desmoplasia).
  • in head = obstruct distal common bile duct ⇒ jaundice.
  • body and tail = silent for long time. large or metastatic when discovered. extensive perineural and vascular invasion.
  • cells form glandular patterns resembling ductal epithelium.
  • adenosquamous carcinoma = squamous and glandular differentiation.
  • undifferentiated carcinoma = multinucleated osteoclast-like giant cells.
• presentation: weight loss and pain. jaundice if in head. metastases common (liver), 80% unresectable at presentation.
  
  • 80% first year mortality.
  • Trousseau syndrome = migratory thrombophlebitis can occur with pancreatic neoplasms.

Question 14

Acinar Cell Carcinoma

Answer 14

• have acinar cell differentiation, zymogen granules, produce exocrine enzymes (trypsin)
• lipase release can cause metastatic fat necrosis in 15%.

Question 15

Pancreotoblastoma

Answer 15

• rare malignant tumor in childhood.
• squamous islands mixed with acinar cells.