pathology lg 4

• Congenital anomalies of pancreas


  • Agenesis
  • Pancreas Divisum
  • Annular Pancreas
  • Ectopic Pancreas
• Agenesis


  Very rare, pancreas is totally absent. Incompatible with life. Caused by germ line mutation in IPF1 (PDX1) gene on chromosome 13.
• Pancreas Divisum


  Clinically significant, caused by failure of duct systems of dorsal and ventral primordia to fuse. Accumulated pancreatic secretions lead to chronic pancreatitis.
• Annular Pancreas


  Develops when the bifid ventral pancreatic primordium or bud forms a band-like ring that encircles the second portion of duodenum. Presents with signs and symptoms of duodenal obstruction such as gastric distention and vomiting.
• Ectopic Pancreas


  Found in 2% of routine postmortem examination. Favored sites are stomach and duodenum, followed by jejunum and ileum. Usually located in submucosa. Histologically: pancreatic acini, occasionally islets. May forms a sessile mass. May cause pain from localized inflammation, or rarely mucosal bleeding. 2% of islet cell tumors arise in ectopic pancreatic tissue.
• Pancreatic cysts


  • Non-neoplastic pseudocysts
  • Congenital cysts
  • Cystic neoplasms
• Pseudocysts


  Lack epithelial lining. Account for 75% of cysts in pancreas. Usually arise after an episode of acute pancreatitis. Traumatic injury to abdomen could be the cause. Many spontaneously resolved, may become secondarily infected, the larger one may compress or even perforate into adjacent structures.
• Congenital Cysts


  Result from anomalous development of pancreatic ducts. Those in kidney, liver, and pancreas coexist in polycystic disease. Range from microscopic lesions to 3-5 cm in diameter. Lined by cuboidal epithelium, or by attenuated cell layer. Filled with serous or mucoid fluid.
• Serous cystadenoma


  Benign, lined by low-cuboidal cells, and contain clear serous fluid.
• Mucinous cystic neoplasms


  Can be benign, borderline, or malignant. Filled with thick tenacious mucin, and lined by columnar mucinous epithelium. Benign cysts: lack cytological or architectural atypia. Borderline cysts: show cytological and architectural atypia, but no tissue invasion. Malignant cysts: have associated tissue invasion.
• Causes of acute pancreatitis

  • Gall stones
  • Alcoholism
  • Hereditary
  • Trauma
  • Idiopathic
• Acute pancreatitis


  Reversible lesion. Pathogenesis: Pancreatic enzymes present in acinar cells in proenzyme form and have to be activated. Lysosomal hydrolases permitting proenzyme activation, and local release of activated enzymes.
• Acute pancreatitis


  • Gross: Swollen edematous, with hemorrhagic and necrotic yellow nodules (represent fat necrosis). Chalky white foci due to calcium deposition in fat necrosis areas (calcium soap).
  • Microscope: Edema by microvascular leakage. Fat necrosis by lipolytic enzymes. Acute inflammatory reaction. Parenchymal (acini) necrosis by Proteolytic enzymes. Destruction of blood vessels with interstitial hemorrhage.
• Chronic pancreatitis


  Irreversible. Inflammation of pancreas with destruction of exocrine pancreas and fibrosis. In late stages: destruction of endocrine pancreas. Pathogenesis: Ductal obstruction by concretions, Toxic-metabolic: alcohol, Oxidative stress: alcohol-induced free radicals, Necrosis-fibrosis: hereditary pancreatitis by autolysis-resistant trypsin molecules.
• Chronic pancreatitis


  • Gross: pancreas is hard, with dilated ducts and visible calcified concretions.
  • Microscope: Acini destruction and reduction in number, parenchymal fibrosis, dilation of pancreatic ducts, and chronic inflammatory cells infiltration.
• Pancreatic cancer


  Pancreatic adenocarcinoma is fourth leading cause of cancer death preceded only by lung, colon, and breast cancers. 5-years survival rate is less than 5%. Precursor lesions: Progression from non-neoplastic epithelium, to noninvasive lesions in small ducts and ductules (PanIN), then to invasive carcinoma.
• Molecular alterations in pancreatic cancer

  • K-RAS oncogene (80-90% of cases)
  • P16 tumor suppressor gene (95% of cases)
  • SMAD4 (DPC4) tumor suppressor gene (55% of cases)
  • P53 tumor suppressor gene (50-70% of cases)
• Pancreatic cancer


  • Grossly: hard, stellate, gray-white, poorly defined masses.
  • Microscopically: Moderate to poorly differentiated adenocarcinoma. Well-differentiated tumors are the exception. Dense fibrous stroma (desmoplastic stroma).
• Diagnosis of pancreatic cancer


  • Gene study: K-RAS oncogene is mutated in 80-90% of cases.
  • Serum levels of tumor markers: Carcinoembryonic Antigen (CEA) and CA19-9 are elevated.
  • Imaging techniques: Endoscopic US and CT scan for diagnosis and performance of needle biopsy.
• Epidemiology, Etiology, clinical course of pancreatic cancer


  • Most cases occur between age 60 and 80 years
  • More common in blacks than whites, and in Jewish decent
  • Risk factors: smoking, diet rich in fats, Chronic pancreatitis and diabetes mellitus
  • 60% of cases arise in head, 15% in body, and 5% in tail ; and in 20% there is diffuse involvement
  • Highly invasive
  • Desmoplastic stroma: intense non-neoplastic host reaction composed of fibroblasts, lymphocytes, and extracellular matrix
  • Most carcinomas of head obstruct the common bile duct and cause jaundice; in contrast, carcinomas of body and tail remain silent for some time
  • The cancer often extend through retroperitoneal space entrapping adjacent nerves
  • Local invasion to surrounding organs (stomach, spleen); and regional L.N's involvement
  • Distant metastases principally to lung and bone
• Less common variants of pancreatic cancers

  • Acinar cell carcinomas
  • Adenosquamous carcinomas
  • Undifferentiated carcinomas
• Acinar cell carcinomas


  Show prominent acinar cell differentiation, including formation of zymogen granules and production of exocrine enzymes including trypsin and lipase.
• Adenosquamous carcinomas


  Have focal squamous differentiation in addition to glandular differentiation.
• Undifferentiated carcinomas


  They contain large multinucleated giant cells.