Pathology of Pancreas

• Agenesis


  Failure to develop
• Pancreas divisum


  • Most common clinically significant anomaly
  • When the foetal duct systems of the pancreatic primordia fail to fuse
• Annular pancreas


  The outcome is a ring of pancreatic tissue that completely encircles the duodenum
• Ectopic pancreas

  • Occur in 2% of population
  • Favoured sites are the stomach and duodenum, followed by the jejunum, Meckel diverticulum and ileum
• Congenital cysts

  Probably result from anomalous ductal development
• Pancreatitis


  Inflammation of pancreas
• Types of pancreatitis

  • Acute
  • Chronic
  • Autoimmune
• Acute pancreatitis


  • Reversible pancreatic injury associated with inflammation
  • Ranging from oedema and fat necrosis to parenchymal necrosis with severe haemorrhage
• Causes of acute pancreatitis

  • Biliary tract disease
  • Alcoholism
  • Gallstones
  • Obstruction of pancreatic duct
  • Tumours
  • Pancreas divisum
  • Choledochoceles
  • Biliary sludge
  • Parasites (ascaris lumbricoides, clonorchis sinensis)
  • Medication (Thiazide diuretics, Azathioprine, Estrogens, Sulphonamides)
  • Infections (Mumps, coxsackie, mycoplasma pneumoniae)
  • Hypertriglyceridemia
  • Hyperparathyroidism
  • Hypercalcemic states
  • Thrombosis
  • Embolism
  • Vasculitis
  • Shock
  • Trauma
  • Inherited genetic defects
• Pathogenesis of acute pancreatitis

  1. Autodigestion of pancreatic substance by inappropriately activated pancreatic enzymes

  2. Pancreatic duct obstruction

  3. Primary acinar cell injury

  4. Defective intracellular transport of proenzymes within acinar cells
• Pancreatic duct obstruction

  • Gallstone or biliary sludge in ampulla result in increased intraparenchymal ductal pressure
  • Accumulation of enzyme rich interstitial fluid
  • Death of adipocytes produce "danger" signals that stimulate periacinar myofibroblasts and leukocytes to release proinflammatory cytokines and other inflammatory mediators
  • Edema may further compromise local blood flow, causing vascular insufficiency and ischemic injury to acinar cells
• Primary acinar cell injury

  • Leading to release of digestive enzymes, inflammation, and autodigestion of pancreatic tissues
  • Oxidative stress generates free radicals in acinar cells, leading to membrane lipid oxidation and activation of transcription factors
  • Increased calcium flux trigger inappropriate activation of digestive enzymes
• Defective intracellular transport of proenzymes within acinar cells

  • In normal acinar cells, digestive enzymes and lysosomal hydrolases are transported in separate pathways
  • If defective, proenzyme activation and release of enzymes
• Morphology of acute pancreatitis

  • Microvascular leakage lead to oedema
  • Necrosis of fat by lipolytic enzymes
  • Acute inflammatory reaction
  • Proteolytic destruction of pancreatic parenchyma
  • Destruction of blood vessels with interstitial haemorrhage
  • Fat necrosis - released fatty acids combine with calcium and form insoluble salts that precipitate in situ
• Macroscopy of acute pancreatitis

  • Red to black haemorrhage
  • Interspersed foci of yellow-white chalky fat necrosis
  • Foci of fat necrosis in extrapancreatic fat
• Microscopy of acute pancreatitis

  • Acute interstitial pancreatitis - mild inflammation, interstitial edema and focal areas of fat necrosis
  • Acute necrotizing pancreatitis - necrosis of acinar and ductal tissues as well as islets of Langerhans
  • Haemorrhagic pancreatitis - extensive necrosis and haemorrhage
• Chronic pancreatitis

  • Characterised by longstanding inflammation and fibrosis of the pancreas with destruction of the exocrine pancreas
  • In its late stages, the endocrine parenchyma is also lost
  • The chief distinction between acute and chronic pancreatitis is the irreversible impairment in pancreatic function
• Causes of chronic pancreatitis

  • Long-term alcohol abuse
  • Long standing pancreatic duct obstruction
  • Tropical pancreatitis
  • Hereditary pancreatitis due to PRSS1 mutation or mutations in the SPINK1 gene encoding trypsin inhibitor
  • Chronic pancreatitis associated with CFTR mutations
• Morphology of chronic pancreatitis

  • Macroscopy - hard, sometimes extremely dilated ducts and calcified concretions
  • Microscopy - parenchymal fibrosis, decreased number and size of acini with relative sparing of islets, variable dilation of pancreatic ducts, chronic inflammatory infiltrate, ductal concretions
• Acute necrotizing pancreatitis

  • Necrosis of acinar and ductal tissues as well as islets of Langerhans
  • Haemorrhagic pancreatitis
  • Extensive necrosis and haemorrhage
• Chronic pancreatitis

  • Characterised by longstanding inflammation and fibrosis of the pancreas with destruction of the exocrine pancreas
  • In its late stages, the endocrine parenchyma is also lost
  • The chief distinction between acute and chronic pancreatitis is the irreversible impairment in pancreatic function in chronic pancreatitis
• Causes of chronic pancreatitis

  • Long-term alcohol abuse
  • Long standing pancreatic duct obstruction
  • Tropical pancreatitis
  • Hereditary pancreatitis due to PRSS1 mutation or mutations in the SPINK1 gene encoding trypsin inhibitor
  • Chronic pancreatitis associated with CFTR mutations
• Morphology of chronic pancreatitis

  • Macroscopy: Hard, sometimes extremely dilated ducts and calcified concretions
  • Microscopy: Parenchymal fibrosis, decreased number and size of acini with relative sparing of islets, variable dilation of pancreatic ducts, chronic inflammatory infiltrate, ductal concretions
• Autoimmune pancreatitis

  • Pathogenically distinct form of chronic pancreatitis associated with IgG4-secreting plasma cells in the pancreas
  • One manifestation of IgG related disease which may involve multiple tissues
  • May mimic the signs and symptoms of pancreatic carcinoma
  • Important to recognize because it responds to steroid therapy
• Morphology of autoimmune pancreatitis

  • Macroscopy: Can mimic cancer (infiltrative mass)
  • Microscopy: Duct centric mixed inflammation, venulitis, increased number of IgG4 producing plasma cells
• Types of pancreatic cysts

  • Pseudocysts
  • True cysts
• Pseudocysts

  • Localised collections of necrotic haemorrhagic material rich in pancreatic enzymes
  • Lack epithelial lining (thus pseudocysts)
  • 75% of pancreatic cysts
  • Usually after an episode of acute pancreatitis
  • Often in the setting of chronic pancreatitis
  • Can also be due to traumatic injury
• Morphology of pseudocysts

  • Usually solitary, 2-30cm
  • May be within the substance of pancreas, more commonly in peripancreatic tissue
  • Formed by walling-off of areas of haemorrhagic fat necrosis with fibrous tissue
  • Central necrotic haemorrhagic material rich in pancreatic enzymes surrounded by nonepithelial lined fibrous walls of granulation tissue
• Pseudocysts


  • Many resolve spontaneously
  • May become secondarily infected
  • Larger may compress or perforate into adjacent structures
• Pancreatic carcinoma


  • Infiltrating ductal adenocarcinoma
  • Fourth leading cause of death in US
  • One of highest mortality rates of any cancer - 5 year survival less than 5%
• Precursors of pancreatic carcinoma

  • Progression from non neoplastic epithelium, to non invasive lesions in small ducts, to invasive carcinoma
  • Pan IN's (pancreatic intraepithelial neoplasias)
• Molecular carcinogenesis of pancreatic carcinoma

  • Like all carcinomas is fundamentally a genetic disease
  • Inherited or acquired mutations
  • Often multiple gene alterations in a single carcinoma
  • The patterns of genetic changes differ from other malignancies
• Epidemiology and inheritance of pancreatic carcinoma

  • Primarily in elderly (80% between 60 to 80 years)
  • Blacks more than whites, Jewish decent
  • Strongest environmental influence is smoking
  • Diet rich in fat has been implicated
  • Increased risk with chronic pancreatitis and DM
  • Familial clustering
  • Inherited genetic syndromes associated with increased risk
• Morphology of pancreatic carcinoma

  • Macroscopy: 60% in head, 15% in body, 5% in tail, 20% diffuse
  • Usually hard, stellate, gray-white, poorly defined
  • Highly invasive
  • In head of pancreas may obstruct CBD and cause marked distention of biliary tree
  • Most have jaundice
  • Often extends through retroperitoneal space entrapping nerves
  • Occasionally invades spleen, adrenals, vertebral column, stomach
  • Frequently involvement of peripancreatic lymph nodes
  • Often liver metastases
  • Distant metastases to lungs and bones
  • Migratory thrombophlebitis in 10%
  • Microscopy: Vast majority, ductal adenocarcinoma
  • Intense non neoplastic reaction (desmoplastic response), dense stromal fibrosis
  • Recapitulate ductal epithelium but invasive growth pattern, atypical, irregular, bizarre
  • Anaplastic cuboidal to columnar epithelium
  • Perineural invasion
  • Lymphatic invasion
• Pancreatoblastoma


  • Most common pancreatic tumor of infancy / early childhood
  • Characterized by acinar differentiation, squamoid corpuscles and stromal bands
• Morphology of pancreatoblastoma

  • Macroscopy: Partially encapsulated, often lobulated, mean diameter 10 cm
  • Microscopy: Mixtures of acini, squamoid corpuscles and less commonly endocrine or ductal features