Pathology of Exocrine

Pancreas

Dr Darli
 GIN: DLO

• Pancreatitis
• Acute***
• Chronic
• Benign cysts & cystic tumours
• Carcinoma of the pancreas**
• Tumours
• Adenocarcinoma
• Other pancreatic tumours
 Exocrine Pancreas
• Synthesis and secretion of digestive enzymes
• Stored as inactive zymogen granules in the cytoplasm of acinar cells
• Premature activation of these granules by ductal
obstruction or trauma- acute pancreatitis
• Release of hydrolytic enzymes- Fat necrosis in peripancreatic
soft tissue

• Function: Alkaline secretion with digestive enzymes and

proenzymes under neural/ vagal (acetylcholine) or
humoral factors- secretin and cholecytokinin of
duodenum (fat and gastric Hcl): TRYPSINOGEN (most) -
TRYPSIN , CHYMOTRYSIN, ELASTASE, AMYLASE,
LIPASE ,PHOSPHOLIPASE
 Pathology of pancreas : L.O

• List types of pancreatitis.

• Describe etio-pathogenesis, morphology, clinical features, complications and
investigations of pancreatitis.
• Morphology of pancreatitis
• Acute: Enlarged and swollen pancreas,Enzymatic fat necrosis & inflammation
• Chronic: Pseudo cyst formation,Fibrosis & atrophied ductal epithelium
• Clinical features of pancreatitis
• Abdominal pain and Shock
• Distended abdomen with free fluid
• Complications of pancreatitis
• Shock, ARDS
• Acute renal failure .
• Investigations of pancreatitis
• Amylase and lipase
• Cholangiogram, ERCP, USG, CT, MRI
 Acute pancreatitis

• Acute pancreatitis
• Interstitial / edematous pancreatitis
• Acute hemorrhagic pancreatitis
• Rare but life-threatening condition
• Chronic pancreatitis
• Mostly chemically induced injury

Sequalae of acute pancreatitis

• Systemic ; Leucocytosis and haemolysis, DIC

• Peripheral vascular collapse, Shock, ARDS, acute renal failure
• Diffuse fat necrosis
• Local, Pancreatic abscess, pseudo-cyst formation
• Regional ; Duodenal obstruction
 Etiology of acute
pancreatitis

Metabolic  Alcohol, drugs, hypercalcemia, genetic

Mechanical  Trauma, gallstones, iatrogenic
Vascular  Shock, embolism, Polyarteritis nodosa
Infection  Mumps, mycoplasma pneumoniae

Eg. ; Gallstones obstructing • Bile stone obstruction

cystic duct/CBD – choledochopancreatic ducts
• High alcohol concentration • Alcohol abuse
• Trauma- external or surgical – Spasm of sphincter of Oddi
– Reflux of bile
Interstitial pancreatitis
• Sterile chemically mediated inflammation
• Injury to exocrine pancreas Grossly; LIPASE RELEASES FATTY
ACID FROM TRIGLYCERIDE
• Mild inflammation MOLECULE TO BIND WITH
• edema of interstitial spaces CALCIUM TO FORM
• Inflammatory cell infiltration SAPONIFICATION- WHITE CHALK.
• Mild raised pancreatic enzymes in serum
• Require no treatment- heal spontaneously

• Enzymatic digestion of pancreatic and peri-

pancreatic tissues and blood vessels
• Release of other digestive enzymes to
peripancreatic tissue and blood vessels
Acute hemorrhagic • Obstruction at choledochopancreatic duct
pancreatitis • Reflux of bile to pancreatic ducts
• Reverse bicarbonate rich juices to acini
• Activate pancreatic lytic enzymes
• Rupture of acini , release enzymes to outside
• Auto-digestion of protein, fat, CHO and BVs
Morphology of acute
pancreatitis

• Gross :Extensive hemorrhagic necrosis of

pancreas , deposition of chalky white necrotic
spots
• Enlarged swollen organ
• Focal necrosis and hemorrhage
• Micro : EzFN
• Necrotic acini, ducts and blood vessels
• Fat necrosis- white chalk (blue in H&E)
• Hemorrhage in tissue
• Acute PMNs+ macrophages

ENZYMES DEGRADE LIPID AND

MEMBRANE PHOSPHOLIPIDS

Micro: N: necrotic fat tissue, H:

surrounded by foamy histiocytes
Most important complications of acute
hemorrhagic pancreatitis
Systemic complications of
• Pseudocyst formation
• Liquefactive necrosis
acute hemorrhagic
• Enclosed by GT pancreatitis ?
• Fibrous capsule • Shock –
• Abscess formation – multi factorial
• 20 to bacterial infection – > permeability by enzyme injury
• High mortality • DIC
– Endothelial injury by enzymes
• Hemorrhagic ascites – Platelet and fibrin thrombi formation
• ARDS
– Shock
– Enzymatic injury to alveolar-capillary unit
– Pulmonary edema and hyaline membrane
• Renal failure
– Consequence of shock
• Subcutaneous fat necrosis
– Lipolytic enzyme digestion
Typical signs and symptoms of acute
hemorrhagic pancreatitis

• Sudden onset of abdominal pain

• Left upper quadrant pain radiating
to back Outcome of acute
• Nausea and vomiting increased
hemorrhagic pancreatitis :
Most recover
by eating •10% mortality (25% in pediatric
• General distress with fever, cases)
sweating, tachycardia and •Unfavourable factors
tachypnea, – Old age
– Severe leucocytosis, Low PCV
• Alcohol ingestion and gallstones
– Increased blood sugar
obstruction are most important – Elevated LFTs
causes of acute pancreatitis – Decreased serum calcium and
which can be confirmed by serial PaO2
serum amylase and lipase – Elevated BUN
estimation.
 Lab tests for acute pancreatitis

• Leucocytosis
• Hypocalcemia after 2-3 days of onset , Hypocalcemia- poor
prognostic sign
• Urinary amylase increased
• Serum amylase/ lipase/ trypsin decreased- Increasing amylase
level, Rising serum lipase after 72 hours- diagnostic
• Sensitive marker (4 x above normal)
• AST, ALT, alkaline phosphatase
• Elevated with liver injury and cholestasis
• Associated with cholelithiasis
Others: CT scan, Enlarged organ
X-ray (Rupture), peritoneal tap for
enzymes estimation
Chronic pancreatitis
• Chronic inflammation with fibrosis
• Firm, reduced size, foci of calcification
• Lymphocyte, macrophages, plasma cells
• Fibrosis, calcification, intraductal concretions
• Loss and atrophy of acini
• Cystic dilatation of distal ducts

Causes of chronic pancreatitis

• Repeated acute attacks
• Chronic alcoholism
• Cystic fibrosis of pancreas
• Familial or idiopathic
• Tropical chronic pancreatitis
CHRONIC PANCREATITIS

PARENCHYMAL FIBROSIS
REDUCED ACINI
ISLET CELLS SPARED
CHRONIC INFLAMMATORY CELL
INFILTRATION
DUCTS DILATED WITH
PROTEIN PLUGS
ACINAR CELL LOSS
SCLEROSIS
HARD AND FIBROSED GLAND
CALCIFIED CONCRETIONS IN
LUMEN OF DUCTS.
 Chronic pancreatitis

Sequelae; Loss of normal exocrine

function , Fat malabsorption :
Possible deficiency of fat soluble vitamins
Marked pain -  surgery
• Islets are resistant to pancreatitis- DM
uncommon complication of chronic
pancreasitis.
• Pseudo-pancreatic cyst formation.

Note fibrosis and loss of acini and intact islet cell of Langerhan
 Clinical features of chronic pancreatitis

• Persistent upper abdominal pain

• Radiation to back
• Precipitated by alcohol
• Fibrosis of nerves
• Malabsorption
• Pancreatic insufficiency
• Steatorrhea, vitamin A,D,E and K deficiency

• DM – loss of islet cells

• Calcification on x-ray
• Distortion of ducts on ERCP (endoscopic retrograde
cholagiopancreatography)
Outcome of chronic pancreatitis
• Incurable debilitating disease
• Relentless pain
• Malabsorption
• Wasting
• DM
• Death due to infection or complications of chronic
alcoholism (3% cumulative death per yearly)

• Pseudocyst formation
Complication of • Duct obstruction
chronic • Malabsorption
pancreatitis • Steatorrhea
• Secondary diabetes- rare.
 CARCINOMA of the PANCREAS

• 5th most common cause of death in US.

Pathogenesis and Genetics ; Incidence higher in smokers
Others ? alcohol, high fat diet , Frequent in chronic
pancreatitis +/_ ? association with diabetes
• familial relapsing pancreatitis significantly associated
with CA panc:
• Point mutations at codon 12 of k-ras in 90% of
panc:cancers
• 60 to 80% - p53 mutations
 Carcinoma pancreas***
• Usually adenocarcinoma
• Desmoplastic stroma
• Head of pancreas- obstruct CBD
• Islet cell destruction - DM
• May have obstructive jaundice
• Weight loss
• thrombophlebitis migrans- Trousseau’s sign
• Very poor prognosis-Liver & regional LN 20 blood spread,
• Etiological association
• Cigarette smoking
• Diabetes mellitus
• Familial pancreatitis • Mucinous tumours
of pancreas
• Intraductal
papillary mucinous
tumours
Ca.Head of pancreas (Ampulla of Vater):
-tumor bulges into duodenal lumen;
-circular, tan, polypoidal mass with central ulceration
- a specimen of pancreatico-duodenectomy
CA head of pancreas:
-ampullary region invaded bile obstruction -> distension of biliary tree
 obstructive jaundice
- ulceration into duodenum

CA body and tail:

-remain silent for a long time
-large and widely disseminated at discovery
-extend to retroperitoneal space
-impinge on nerves
 -invade spleen, adrenals ,vertebra colon,stomach
-peripancreatic , gastric ,mesenteric , omental, portahepatic nodes
-metastases to liver , lungs, bones
Histology:
-moderately to poorly differentiated adenocarcinoma
-abortive tubules or cell clusters
-aggressive deeply infiltrative growth
-stromal fibrosis
-10% adenosquamous or
giant cell type or sarcomatoid pattern
-rarely acinar cell CA
Adenocarcinoma of the pancreas:
• most common in head region, arise from
duct epithelium, as painless obstructive
jaundice
•P: normal pancreatic parenchyma
•T: tumor area- ductal pattern with marked
variation in size and shape of the neoplastic
gland-like spaces
clinical Features:
-silent until extension impinges on other structures
-pain when erode nerve fibers
-obstructive jaundice
-weight loss, malaise, weakness
-migratory thrombophlebitis in 10%
less than 15% resectable at diagnosis
-screening for k-ras mutations
-serum CEA and CA 19-9 raised
-USG and CT great value in diagnosis
-percutaneous needle biopsy can obviate need for
laparotomy
Pancreatic
adenocarcinoma-
head

Pancreatic diseases mostly remain

occult due to its retroperitoneal
location and lack obvious palpable
mass in the abdomen.
Other Pancreatic tumours
• These are unusual tumours so called
• Solid and cystic neoplasms of Pancreas
• Occur in younger patients
• More indolent course than ductal carcinomas
• Pancreatic acinar cell carcinoma are quite rare
• Serous cystadenomas – benign glycogen filled cells
• Islet of Langerhans cells can give rise to NE tumours.
Islet of Langerhans tumour
Cystic pancreatic neoplasm in children
• Microcystic adenoma
• Cystadenocarcinoma
• Rare lesions
• Appearance is similar as in adults
• May cause pseudomyxeoma peritonei if they rupture in peritoneum.

True cysts:
lined by epithelium,
may be congenital or
benign cystadenoma or
malignannt cystadenocarcinoma
Pancreatic pseudocysts:
lack of epithelium,
often result from acute pancreatitis
Sum-up: Pancreatitis
• Acute pancreatitis- inflammation, reversible parenchymal damage, edema, fat
necrosis, hage- mild abdominal pain to fatal vascular collapse
• Chronic pancreatitis- Irreversible parenchymal damage and scar- malabsorption
or DM
• For Both- alcohol and duct obstruction are most common cause

• Sum-up: Neoplasms of Pancreas :

• Most pancreatic cancers arise from PINs (pancreatic intraepithelial neoplasm)
via multistep carcinogenesis of oncogenes (K-ras and p53).
• Most are Ductal adenocarcinomas- have dense stroma, aggressive, high
mortality rate
• Ca head- presents with obstructive jaundice.