Patho chapter 16

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• Pancreas absent b.c.o mutation in PDX1 gene on chromosome 13q12.1 – encodes for "Pancreatic Duodenal Homeobox 1" (transcription factor needed for formation) Agenesis
• Failure of closing of ducts system of fetal pancreatic primordial. Person has incr. intraductal pressure & incr. risk of chronic pancreatitis. Pancreas Divusum
• uncommon variant of pancreatic fusion. Results in a ring of pancreatic tissue around duodenum. Asymptomatic - may present with gastric distention & vomitting. Annular pancreas
• Abnormal dev. of pancreatic ducts. Forms congenital cysts which can be unilocular, range in size. Lined by uniform cuboidal or flattened epith. Enclosed in a thin, fibrous capsule. Contains clear serous fluid.
• Weirdly situated pancreas (stomach, duodenum, jejunum, meckel's diverticulum, stomach). Small, embryologic rests in submucosa composed of normal pancreatic acini with occasional islets. Asymptomatic - but pain can occur b.c.o localized inflammation. Ectopic pancreas
• Acute pancreatitis is a reversible inflammatory disorder that varies in severity, ranging fr. focal edema and fat necrosis to widespread hemorrhagic parenchymal necrosis .
• 80 % of cases of acute pancreatitis is caused by biliary tract disease or alcoholism
• Other less common causes of acute pancreatitis could be... obstruction, medications, metabolic disorders, ischemia, trauma, inherited.
• Which gene encoding pancreatic enzymes or their inhibitors is mutated in acute pancreatitis? SPINK1 gene
• An autosomal dominant disease with recurrent attacks of severe inflammation in pancreas. Caused by mutations in PRSS1 gene. The defect leads to hyperactivation of trypsin & other enzymes & autodigestion & injury. Hereditary pancreatitis
• 1. edema 2. fat necrosis 3. acute inflammation 4. destruction of parenchyma 5. Destruction of blood vessels Basic alterations in acute pancreatitis
• Edema in acute pancreatitis is caused by microvasicular leakage
• Fat necrosis i acute pancreatitis is caused by enzymatic destruction by lipases
• Destruction of pancreatic parenchyma in acute pancreatitis is caused by proteolytic destruction
• Destruction of blood vessels in acute pancreatitis leads to interstitial hemorrhage
• Red-black hemorrhagic areas interspersed with foci of yellow-white, chalky fat necrosis Acute necrotizing pancreatitis
• What happens if trypsin is inappropriately generated? You get activation of enzymes , autodigestion & defective clotting & complement system
• Symptoms of acute pancreatitis includes abdominal pain an ominous absence of bowel sounds.
• Laboratory findings in acute pancreatitis includes elevated levels of amylase & lipase
• Liquefied areas of necrotic pancreatic tissue becoming walled of by fibrous tissue to form a space, in acute pancreatitis. Pancreatic Pseudocysts
• What are the possible complications of pseudocysts? they can compress or even perforate into adjacent structures
• Where can pseudocyst be found, in acute pancreatitis? attached to surface of glands & peripancreatic tissue (e.g lesser omental sac or retroperitoneum)
• What are pseudocysts composed of? necrotic debris encased by fibrous walls of granulation tissue lacking epithelial lining
• chronic pancreatitis is characterized by long-standing inflammation, fibrosis, destruction of exocrine pancreas & eventually also the endocrine part.
• What are the differences between acute & chronic pancreatitis? the irreversible impairment in pancreatic function
• Most common cause of chronic pancreatitis is? long-term alcohol use
• What are other causes of chronic pancreatitis? long-standing obstruction, topical pancreatitis, hereditary pancreatitis, CFTR mutations
• Chronic pancreatitis is characteristic for parenchymal fibrosis, reduced size & no. of acini and variable dilations of pancreatic ducts.
• What happens to the islet of Langerhans in chronic pancreatitis? They're relatively spared, but they become embedded in the sclerotic tissue - may fuse & look enlarged.
• What happens to the ductal epithelia in chronic pancreatitis? They may be atrophied, hyperplastic, or squamous metaplastic - with ductal concentrations
• A distinct form of of chronic pancreatitis characterized by either: (1) Lyphoplasmocytic sclerosing pancreatitis (2) idiopathic duct centric pancreatitic Autoimmune Pancreatitis
• Autoimmune pancreatitis: A striking infiltration of the pancreas by lymphoplasmocytic infilatrtion - with many IgG4 & "swirling fibrosis" and venulitis Lymphoplasmocytic sclerosing pancreatitis
• Autoimmune pancreatitis: A ductcentric mixed infliltrate composed of neutrophils, lymphocytes & plasma cells, often oblitering the ductal epithelium idiopathic duct centric pancreatitis
• Bening, 25% of all pancreatic cystic neoplasms. Composed of glycogen rich cuboidal cells surrounding small cysts. Contain clear, straw-colored fluid. Common in 7th decade of life. Nonspecific symptoms. Most carry somatic mutations of Von Hippel Lindau (VHL) tumor suppressor gene. Serous cystadenomas
• Can be both malignant or bening but 95 % arise in women, in body or tails of pancreas. Manifest as painless, slow-growing, masses. Filled with thick, tenacious mucin & lined by columnar mucinous epithelium. Has low-grade, moderate, high-grade dysplasia. Mucinous cystic neoplasms
• Benign, MALE PREDOMINANCE, mucin producing intraductal neoplasms. Involve the HEAD of pancreas - arise pancreatic ducts. Is dysplastic. 2/3 have oncogenic mutations in GNAS gene - on chromosome 20q13. Intraductal Papillary Mucinous Neoplasms
• Fourth cause of cancer death in US, VERY poor prognosis. Arises b.c.o mutations in KRAS, P16, SMAD4, TP53, VHL (GNAS) gene. Most common lesions are PanINs. Pancreatic carcinoma
• What is PanINs? The most common lesions of pancreatic cancer arising in ducts & ductules.
• The most common lesions of pancreatic cancer arising in ducts & ductules near infiltrating carcinoma. Has (1) dramatic telomere shortening (2) share genetic alterations with adjacent carcinoma (3) progresses with more accum. of chromosomal abnormalities PanINs (1a, 1b, 2, 3 --> invasive carcinoma)
• What cane make pancreatic carcinomas worsen? Smoking, chronic pancreatitis, diabetes mellitus
• Where do most pancreatic cancers arise? In head of pancreas
• Morphology of pancreatic carcinomas Hard, gray-white, stellate, poorly defined
• Pancreatic carcinomas forming glands & secrering mucin - by recapitulating the normal duct epithelium Ductal adenocarcinomas
• What are the two main characters of pancreatic carcinomas? They are highly invase & they elicit the desmoplastic response
• An intense non-neoplastic host reaction composed of fibroblasts, lymphocytes & extracellular matrix is known as a desmoplastic response b.c.o e.g. increased Growth factors
• Most carcinomas of the head of pancreas obstruct the distal common bile duct as it courses through the head of the pancreas. Patient usually has distention in biliary tree & jaundice.
• Why do pancreatic carcinomas of the body & tail remain silent for some time? Because they don't impinge on the biliary tract
• Less common variant of pancreatic carcinoma. Has focal squamous differentiation and glandular differentiation. Adenosquamous carcinomas
• Less common variant of pancreatic carcinoma. Of monocyte lineage intermixed within the neoplasm. Undifferentiated carcinomas with osteoclast-like giant cells
• What are the clinical features of pancreatic carcinomas? Obstructive jaundice, TROUSSE SYNDROME, weight loss, anorexia, generalized malaise, weakness.
• A hypercoagulobility syndrome associated with cancer. Caused by incr. procoagulants. Also known as migratory thrombophlebitis. Trousseau syndrome
• Which one of the PanNETs has good prognosis and low rate of malignancy? Insulinoma

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