PATHOLOGY OF THE PATHOLOGY OF THE

PANCREASPANCREASIsmail Matalka , MRCPathIsmail Matalka , MRCPath

Department of PathologyDepartment of Pathology

Faculty of MedicineFaculty of Medicine

Jordan University of Science & TechnologyJordan University of Science & Technology

Irbid - JordanIrbid - Jordan

ANATOMY & HISTOLOGY OF THEANATOMY & HISTOLOGY OF THEP A N C R E A SP A N C R E A S

• 15 cm in length, 60-140 gm, consists of head, body & 15 cm in length, 60-140 gm, consists of head, body & tail; pancreatic duct empty into duodenum or common tail; pancreatic duct empty into duodenum or common bile ductbile duct

• Histologically, consists of 2 components:Histologically, consists of 2 components:– 1) 1) ExocrineExocrine: 80-85%, consists of numerous glands : 80-85%, consists of numerous glands

(acini) lined by columnar basophilic cells (acini) lined by columnar basophilic cells containing zymogen granules, which form lobules; containing zymogen granules, which form lobules; ductal systemductal system• Trypsin, chemotrypsin, aminopeptidase, amylase Trypsin, chemotrypsin, aminopeptidase, amylase

– 2) 2) EndocrineEndocrine: islets of Langerhans, which are : islets of Langerhans, which are invaded by capillaries. Islets consist of:invaded by capillaries. Islets consist of:• 4 main cell types: B (insulin), A (glucagon), D 4 main cell types: B (insulin), A (glucagon), D

(somatostatin), PP cells (pancreatic polypeptide) (somatostatin), PP cells (pancreatic polypeptide) • 2 minor cell types: D1 (VIP) & enterochromaffin 2 minor cell types: D1 (VIP) & enterochromaffin

cells (serotonin)cells (serotonin)

DISEASES OF THEDISEASES OF THEP A N C R E A SP A N C R E A S

• Congenital anomalies:Congenital anomalies:– Agenesis, hypoplasia, ectopia, duct anomaliesAgenesis, hypoplasia, ectopia, duct anomalies

• Exocrine pancreas:Exocrine pancreas:– Cystic fibrosisCystic fibrosis– Acute pancreatitisAcute pancreatitis– Chronic pancreatitisChronic pancreatitis– Carcinoma of the pancreasCarcinoma of the pancreas

• Endocrine pancreas:Endocrine pancreas:– Diabetes mellitusDiabetes mellitus– Islet cell tumorsIslet cell tumors

CONGENITAL ANOMALIES OF

THE PANCREAS• Agenesis:Agenesis: usually associated with widespread usually associated with widespread

severe malformations that are incompatible with severe malformations that are incompatible with lifelife

• Hypoplasia:Hypoplasia: both endocrine & exocrine elements both endocrine & exocrine elements may be involvedmay be involved

• Annular pancreas:Annular pancreas: pancreas head encircle pancreas head encircle duodenum & may cause obstructionduodenum & may cause obstruction

• Aberrant (ectopic) pancreas:Aberrant (ectopic) pancreas: 2%; mostly in 2%; mostly in stomach, duodenum, jejunum, Meckelstomach, duodenum, jejunum, Meckel’’s s diverticulum & ileumdiverticulum & ileum

• Ducts anomalies:Ducts anomalies: duct of Wirsung may drain into duct of Wirsung may drain into common bile duct or an orifice high in the common bile duct or an orifice high in the duodenumduodenum

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

C Y S T I C F I B R O S I SC Y S T I C F I B R O S I S• CF is the CF is the most common lethal genetic diseasemost common lethal genetic disease that that

affects white populations (1 in 2000 live births)affects white populations (1 in 2000 live births)• Characterized by abnormally Characterized by abnormally viscid mucous viscid mucous

secretionssecretions that block airways & pancreatic ducts that block airways & pancreatic ducts & are responsible for:& are responsible for:– 1) Recurrent chronic 1) Recurrent chronic pulmonarypulmonary infections infections– 2) 2) PancreaticPancreatic insufficiency insufficiency

• High level of High level of NaCl in sweatNaCl in sweat• Pathognesis:Pathognesis: primary defect in transport of Cl primary defect in transport of Cl

__

across epithelia. The cAMP-dependent Clacross epithelia. The cAMP-dependent Cl_ _

channels (CF transmembrane conductance channels (CF transmembrane conductance regulator [regulator [CFTRCFTR]) are defective.]) are defective.

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

C Y S T I C F I B R O S I SC Y S T I C F I B R O S I S• CF gene is located on chromosomeCF gene is located on chromosome 7 7 with up to 300 with up to 300

mutations identified in this gene so far.mutations identified in this gene so far.• Pancreatic pathology: Pancreatic pathology: abnormalities are seen in 85% of abnormalities are seen in 85% of

patients: patients: – mucus accumulation, mucus accumulation, – duct dilation & plugging, duct dilation & plugging, – exocrine gland atrophy. Islets usually spared. exocrine gland atrophy. Islets usually spared. – Ducts may be converted into cysts seperated only by Ducts may be converted into cysts seperated only by

islets of Langerhans & fibrous stroma (islets of Langerhans & fibrous stroma (fibrocystic fibrocystic disease of pancreasdisease of pancreas))

– Malabsorption syndrome: particularly fatMalabsorption syndrome: particularly fat– Squamous metaplasia of duct liningSquamous metaplasia of duct lining

• Meconium ileus, pulmonary problemsMeconium ileus, pulmonary problems• Rx:Rx: gene therapy gene therapy

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

ACUTE PANCREATITISACUTE PANCREATITIS• Inflammation of the pancreas, which is almost always Inflammation of the pancreas, which is almost always

associated with acinar cell injuryassociated with acinar cell injury• A clinical & histologic spectrum of severity & durationA clinical & histologic spectrum of severity & duration• Etiologic factors:Etiologic factors:– 1) Metabolic: 1) Metabolic: alcoholalcohol, hyperlipoproteinemia, , hyperlipoproteinemia,

hypercalcemia, drugs (e.g. thiazides), genetichypercalcemia, drugs (e.g. thiazides), genetic– 2) Mechanical: 2) Mechanical: gallstonesgallstones, traumatic & perioperative , traumatic & perioperative

injuryinjury– 3) Vascular: shock, atheroembolism, polyarteritis 3) Vascular: shock, atheroembolism, polyarteritis

nodosanodosa– 4) Infections: Mumps, Coxsackie virus, Mycoplasma4) Infections: Mumps, Coxsackie virus, Mycoplasma– 5) Idiopathic : 10-20% ; ? Genetic basis5) Idiopathic : 10-20% ; ? Genetic basis

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

ACUTE PANCREATITISACUTE PANCREATITIS• Pathology:Pathology:– 4 basic alterations:4 basic alterations:• 1) Proteolytic destruction of pancreatic substance1) Proteolytic destruction of pancreatic substance• 2) Necrosis of blood vessels & interstitial 2) Necrosis of blood vessels & interstitial

hemorrhagehemorrhage• 3) Fat necrosis by lipolytic enzymes3) Fat necrosis by lipolytic enzymes• 4) Associated acute inflammatory reaction4) Associated acute inflammatory reaction

– Pathologic lesions:Pathologic lesions:• a. Acute pancreatic necrosisa. Acute pancreatic necrosis• b. Acute hemorrhagic pancreatitisb. Acute hemorrhagic pancreatitis• c. Suppurative peritonitisc. Suppurative peritonitis• d. Pancreatic pseudocystsd. Pancreatic pseudocysts

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

ACUTE PANCREATITISACUTE PANCREATITIS• Pathogenesis:Pathogenesis:– Autodigestion of pancreatic tissue by inappropriately Autodigestion of pancreatic tissue by inappropriately

activated pancreatic enzymesactivated pancreatic enzymes– TrypsinTrypsin has a major role: has a major role:• a. Activates other proenzymes a. Activates other proenzymes

(proelastase(proelastase , ,prophospholipase )prophospholipase )• b. Converts prekallikrein to kallikrein (Kinin system)b. Converts prekallikrein to kallikrein (Kinin system)• c. Hageman factor is activatedc. Hageman factor is activated

– Mechanisms of pancreatic enzyme activation:Mechanisms of pancreatic enzyme activation:• 1) Pancreatic duct obstruction1) Pancreatic duct obstruction• 2) Primary acinar cell injury2) Primary acinar cell injury• 3) Defective intracellular transport of proenzymes 3) Defective intracellular transport of proenzymes

within acinar cellswithin acinar cells

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

ACUTE PANCREATITISACUTE PANCREATITIS• Clinical features:Clinical features:– Abdominal pain is the cardinal manifestation: Abdominal pain is the cardinal manifestation:

epigastric, radiating to back, variable in severityepigastric, radiating to back, variable in severity– Shock: due to pancreatic hemorrhage & release Shock: due to pancreatic hemorrhage & release

of vasodilatory agents (BK & PGs)of vasodilatory agents (BK & PGs)• Lab:Lab: serum amylase and lipase; serum amylase and lipase; Ca; Ca; bilirubin, bilirubin, glucose & glycosuria glucose & glycosuria• CT scan:CT scan: inflammation, pseudocysts inflammation, pseudocysts• Px:Px: severe cases have high mortality rate (20-40%) severe cases have high mortality rate (20-40%)• Death due to:Death due to: 1) shock, 2) secondary abdominal 1) shock, 2) secondary abdominal

sepsis, 3) adult respiratory distress syndromesepsis, 3) adult respiratory distress syndrome

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

CHRONIC PANCREATITISCHRONIC PANCREATITIS• Repeated boutsRepeated bouts of mild to moderate pancreatic of mild to moderate pancreatic

inflammation, with continued inflammation, with continued lossloss of pancreatic of pancreatic parenchyma & replacement by parenchyma & replacement by fibrousfibrous tissue tissue

• Distinction from acute pancreatitisDistinction from acute pancreatitis may be may be difficult; distinction is made if there is evidence of difficult; distinction is made if there is evidence of previous attacks previous attacks

• Middle-aged men, mostly in Middle-aged men, mostly in alcoholicsalcoholics but may but may due to biliary tract disease, hyperlipoproteinemia due to biliary tract disease, hyperlipoproteinemia & hypercalcemia; no apparent cause in 50% of & hypercalcemia; no apparent cause in 50% of casescases

• PathogenesisPathogenesis: – Protein hypersecretion from acinar cellsProtein hypersecretion from acinar cells– Precipitation of proteins forming ductal plugsPrecipitation of proteins forming ductal plugs– Plugs enlarge forming laminar aggregatesPlugs enlarge forming laminar aggregates

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

CHRONIC PANCREATITISCHRONIC PANCREATITIS• Pathology:Pathology:– Hard organ with dilated ducts & calcified concretionsHard organ with dilated ducts & calcified concretions– Fibrosis, chronic inflammatory cells, obstruction of Fibrosis, chronic inflammatory cells, obstruction of

ducts by protein plugsducts by protein plugs– Extensive atrophy of exocrine glandsExtensive atrophy of exocrine glands– PseudocystsPseudocysts

• Clinical features:Clinical features:– Repeated attacks of abdominal pain or may be silentRepeated attacks of abdominal pain or may be silent

• Dx:Dx: clinical suspicion, lab & CT clinical suspicion, lab & CT• Px:Px: chronic disabling disease due to its major chronic disabling disease due to its major

complications: pancreatic insufficiency & diabetes complications: pancreatic insufficiency & diabetes mellitusmellitus

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

PANCREATIC CARCINOMA PANCREATIC CARCINOMA• Malignant epithelial neoplasm of Malignant epithelial neoplasm of exocrineexocrine portion portion

of pancreasof pancreas• 5th5th most frequent cause of death from cancer most frequent cause of death from cancer• Increasing in incidence in the WestIncreasing in incidence in the West• Peak incidence: Peak incidence: 60 - 80 years60 - 80 years• Cause is unknown; more frequent in smokersCause is unknown; more frequent in smokers• Location:Location:– Head of pancreas 60%Head of pancreas 60%– Body of pancreas 15%Body of pancreas 15%– Tail of pancreas 5%Tail of pancreas 5%– Diffuse involvement 20%Diffuse involvement 20%

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

PANCREATIC CARCINOMA PANCREATIC CARCINOMA• Gritty gray hard massesGritty gray hard masses• Vast majority are Vast majority are adenocarcinomasadenocarcinomas, with poorly , with poorly

formed glands and densely fibrous stromaformed glands and densely fibrous stroma• Carcinoma of Carcinoma of pancreatic headpancreatic head: invasion of : invasion of

ampullary region with bile outflow obstruction, & ampullary region with bile outflow obstruction, & distension of biliary treedistension of biliary tree

• Carcinoma of Carcinoma of body & tailbody & tail: no impingement on : no impingement on biliary tract & remain silent for longer periodsbiliary tract & remain silent for longer periods

• Extends into retroperitoneal spaces, infiltrate Extends into retroperitoneal spaces, infiltrate nerves, abdominal organs & lymph nodesnerves, abdominal organs & lymph nodes

• Distant metastasis to lungs, bone, ..Distant metastasis to lungs, bone, ..

DISEASES OF THE EXOCRINE PANCREASDISEASES OF THE EXOCRINE PANCREAS

PANCREATIC CARCINOMA PANCREATIC CARCINOMA• Clinical features:Clinical features:– Usually silent until its extension impinges on Usually silent until its extension impinges on

other structuresother structures– Pain is usually the first symptomPain is usually the first symptom– Obstructive jaundiceObstructive jaundice– TrousseauTrousseau’’s syndrome: Migratory s syndrome: Migratory

thrombophlebitis (phlebothrombosis) thrombophlebitis (phlebothrombosis) • Lab:Lab: tumor markers, e.g. CEA, CA19-9 Ag are tumor markers, e.g. CEA, CA19-9 Ag are

nonspecificnonspecific• Dx:Dx: CT scan & percutaneous biopsy CT scan & percutaneous biopsy• Px: Px: 1 year survival is 10%; 5 yr survival is 2.5%1 year survival is 10%; 5 yr survival is 2.5%