General Pathology (Laboratory) / Pancreas

2013

ACUTE PANCREATITIS Acute pancreatitis is reversible pancreatic parenchymal injury associated with inflammation. autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes inappropriate activation of trypsinogen is an important triggering event in acute pancreatitis first 24 hours ----> marked elevation of serum amylase levels within 72 to 96 hours ----> rising serum lipase level Hypocalcemia: from precipitation of calcium soaps in necrotic fat Mechanisms 1. Pancreatic duct obstruction. Gallstones or biliary sludge impacted in the region of the ampulla of Vater can raise intrapancreatic ductal pressure and lead to the accumulation of enzyme-rich fluid in the interstitium. Lipase - one of the few enzymes secreted in an active form - cause local fat necrosis - Injured tissues, periacinar myofibroblasts, and leukocytes release proinflammatory cytokines including IL-1, IL-6, tumor necrosis factor, platelet-activating factor, and substance P ----> local inflammation & interstitial edema through a leaky microvasculature - Edema ----> further compromise local blood flow ----> vascular insufficiency & ischemic injury to acinar cells. Primary acinar cell injury most clearly involved in the pathogenesis of acute pancreatitis caused by: - certain viruses (e.g., mumps) - drugs - direct trauma to the pancreas - pancreatitis following ischemia or 3.

shock Defective intracellular transport of proenzymes within acinar cells normal acinar cells: digestive enzymes and lysosomal hydrolases are transported in separate pathways. pancreatic proenzymes: inappropriately delivered to the intracellular compartment containing lysosomal hydrolases ----> proenzymes are then activated ----> lysosomes disrupted ----> activated enzymes released

Morphology wide areas of lightly stained structure less areas ----> shadowy outlines of fat cells ranges from trivial inflammation and edema to severe extensive necrosis and hemorrhage basic alterations: 1) microvascular leakage causing edema 2) necrosis of fat by lipolytic enzymes 3) acute inflammation 4) proteolytic destruction of pancreatic parenchyma 5) destruction of blood vessels and subsequent interstitial hemorrhage acute interstitial pancreatitis - milder form - mild inflammation, interstitial edema, and focal areas of fat necrosis in the substance of the pancreas and in peripancreatic fat Fat necrosis - from enzymatic activity of lipase - released fatty acids combine with calcium to form insoluble salts that impart a granular blue microscopic appearance to the fat cells acute necrotizing pancreatitis - severe form - acinar and ductal tissues as well as the islets of Langerhans are necrotic - Vascular injury can lead to hemorrhage into the parenchyma of the pancreas - pancreatic substance shows areas of redblack hemorrhage interspersed with foci of yellow-white, chalky fat necrosis - Foci of fat necrosis may also be found in extra-pancreatic collections of fat, such as

2.

Ow Meng / Medicine 2015

General Pathology (Laboratory) / Pancreas

2013

the omentum and the mesentery of the bowel, and even outside the abdominal cavity, such as in the subcutaneous fat - peritoneal cavity contains a serous, slightly turbid, brown-tinged fluid in which globules of fat (derived from the action of enzymes on adipose tissue) hemorrhagic pancreatitis - more severe - extensive parenchymal necrosis is accompanied by dramatic hemorrhage within the substance of the gland

SCLEROSIS OF ISLETS OF LANGERHANS large patches of fibrosis some islets within these areas of fibrosis

CYSTIC FIBROSIS bi-allelic inherited mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene decrease bicarbonate secretion by pancreatic ductal cells protein plugging ----> chronic pancreatitis disorder of ion transport in epithelial cells that affects fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal, and reproductive tracts abnormally viscous secretions ----> obstruct organ passages ----> - chronic lung disease secondary to recurrent infections - pancreatic insufficiency - steatorrhea - malnutrition - hepatic cirrhosis - intestinal obstruction - male infertility Morphology ducts are dilated and plugged with eosinophilic mucin, and the parenchymal glands are atrophic and replaced by fibrous tissue nonclassic cystic fibrosis - quite mild and does not seriously disturb their growth and development.

Severe pancreatic involvement ---> impairs intestinal absorption because of the pancreatic achylia ---> malabsorption stunts development and post-natal growth. mucus secretion defect ----> defective mucociliary action, obstruction of bronchi and bronchioles, & crippling fatal pulmonary infections sweat glands are morphologically unaffected milder cases: accumulations of mucus in the small ducts with some dilation of the exocrine glands more severe cases - usually seen in older children or adolescents - ducts are completely plugged ----> atrophy of the exocrine glands & progressive fibrosis - Atrophy of the exocrine portion of the pancreas may occur ----> leaving only the islets within a fibrofatty stroma - loss of pancreatic exocrine secretion impairs fat absorption - avitaminosis A ----> squamous metaplasia of the lining epithelium of the ducts in the pancreas, which are already injured by the inspissated mucus secretions - thick viscid plugs of mucus may also be found in the small intestine of infants ----> small-bowel obstruction, known as meconium ileus. PANCREATIC ADENOCARCINOMA Infiltrating ductal adenocarcinoma of the pancreas: pancreatic cancer precursor lesions: pancreatic intraepithelial neoplasias (PanINs) cigarette smoking Morphology clusters of moderately differentiated glandular structures infiltrating the stroma parenchyma is replaced by fibrous tissue 60% arise in the head of the gland 15% in the body 5% in the tail 20% the neoplasm diffusely involves the entire gland. usually hard, stellate, gray-white, poorly defined masses

Ow Meng / Medicine 2015

General Pathology (Laboratory) / Pancreas

2013

ductal adenocarcinomas: Recapitulate to some degree normal ductal epithelium by forming glands and secreting mucin Two features: - highly invasive (even early invasive pancreatic cancers extensively invade peripancreatic tissues) - elicits an intense non-neoplastic host reaction composed of fibroblasts, lymphocytes, and extracellular matrix (called a desmoplastic response). Most carcinomas of the head of the pancreas - obstruct the distal common bile duct as it courses through the head of the pancreas ----> marked distention of the biliary tree in about 50% of patients with carcinoma of the head of the pancreas ----> jaundice. carcinomas of the body and tail - do not impinge on the biliary tract and hence remain silent for some time. - may be quite large and most are widely disseminated by the time they are discovered. often grow along nerves and invade into the retroperitoneum. can directly invade the spleen, adrenals, vertebral column, transverse colon, and stomach Peripancreatic, gastric, mesenteric, omental, and portahepatic lymph nodes are frequently involved Distant metastases occur, principally to the liver, lungs, and bones. Microscopically, there is no difference between carcinomas of the head of the pancreas and those of the body and tail of the pancreas. moderately to poorly differentiated adenocarcinoma forming abortive tubular structures or cell clusters and showing an aggressive, deeply infiltrative growth pattern Dense stromal fibrosis accompanies the invasive cancer, and there is a proclivity for perineural invasion within and beyond the organ. Lymphatic and large vessel invasion are also commonly seen. The malignant glands are poorly formed and are usually lined by pleomorphic cuboidal-tocolumnar epithelial cells. Less common variants of pancreatic cancer: - adenosquamous carcinomas - colloid carcinoma

hepatoid carcinoma medullary carcinoma signet-ring cell carcinoma, undifferentiated carcinoma - undifferentiated carcinomas with osteoclast-like giant cells. Adenosquamous carcinomas: focal squamous differentiation in addition to glandular differentiation undifferentiated carcinomas: may contain large multinucleated osteoclast-like giant cells.

Ow Meng / Medicine 2015