PATHOLOGY

OF THE
HEPATOBILIARY SYSTEM
AND PANCREAS

Mennen A. Alsol, MD
Normando C. Gonzaga, MD
Lorna B. Lioanag, MD
 Diseases of the Gallbladder
• Cholelithiasis (cholesterol/pigment
stones)
• Cholecystitis (acute/chronic)
• Cholesterolosis (strawberry
gallbladder)
• Tumors (adenocarcinoma)
 Gallbladder
• Clinically important organ but not essential for life
• Stores bile
• NO muscularis mucosa or submucosa
• Histology:
• Mucosal lining: single layer of columnar
cells
• Fibromuscular layer
• Serosa: fats, blood vessels
Chronic cholecystitis
with cholesterolosis:

Cholelithiasis: Cholesterol
& pigment stones
Risk factors for Cholelithiasis:
• Female
• Obesity
• > 40 y/o
• Drugs: hormones
that ↑ cholesterol
excretion or ↓ bile
salts level
Possible outcomes for Cholelithiasis:
• Remain asymptomatic (vast majority)
♦ Cholecystitis (acute/chronic)
• Perforation
• Empyema
• Cholangitis
• Obstruction of common bile duct
• Gallstone ileus
• Hydrops (mucocoele)
• Pancreatitis
• Carcinoma ?
 Acute Acalculous Cholecystitis:
• 5-10% of gallbladder removed for clinical
acute cholecystitis
• impaired blood supply to gallbladder:
• multi-organ failure
• severe burns / severe trauma
• post-operative state / post-partum state
• prolonged hyperalimentation
• gangrene & perforation more common
 Chronic Cholecystitis:
• With or without preceding episodes of
acute cholecystitis
• Obstruction of outflow is not necessary
• Thickened, fibrotic gallbladder wall
• Dystrophic calcification (Porcelain GB)
• Hydrops gallbladder
 Cholangitis:
• Obstruction (choledocholithiasis; indwelling
stents; neoplasms, strictures; parasitism;
pancreatitis)
• Gram (-) bacteria: Klebsiella; Enterobacter;
Clostridium; Bacteroides; grp D Streptococci
• Complications:
• suppurative cholangitis
• ascending cholangitis
• hepatic abscess
• sepsis
 Neoplasms of Gallbladder:

• Adenoma (10% - focal malignant change)

• Carcinoma (Adenocarcinoma - 95%)
• women > 60 y/o
• 60-90% ~ gallstones
• < 5% 5-yr survival rate
 Adenocarcinoma in Gallbladder

Adenocarcinoma of GB appear as raised ulcerated area in the

fundus (T). Most tumors have invaded the wall at the time of
diagnosis, spreads via lymphatic, as well as direct growth in
adjacent tissue.
 Diseases of the Exocrine
Pancreas

• Acute pancreatitis
• Chronic pancreatitis
• Carcinoma
 Acute Pancreatitis
Edematous, often hemorrhagic
pancreas (H), followed by necrosis
and liquefaction.

Focal fat necrosis, due to release of

lipase, are seen as white spots (F) in
mesenteric and peritoneal fat.

Focal necrosis of adipose tissue (F)

with adjacent reactive inflammatory
infiltrates (I).
 Chronic Pancreatitis
1) chronic inflammation
2) fibrous scarring
3) loss of parenchymal
elements
4) duct strictures & ectasia
Atrophic pancreas (P) replaced
by rubbery, fibrous tissue.
Ducts are dilated (D), the
w/ intrapancreatic
duodenum is attached (A) calculi formation
Carcinoma of the Pancreas: 99% adenoCA
Distribution: 60% head; 20% diffuse; 10%
body; 10% tail
Risk factors: cigarette smoking; high
fat/meat intake; hx of gastrectomy/pancreatitis
Pancreatic duct adenocarcinoma:
Cirrhosis
Causes of Cholestasis:
1) intrahepatic
a) liver damage
b) Dubin-Johnson syndrome
(transport problem)
2) extrahepatic
a) obstruction
A. Acute hepatitis with resolution B. Progression to chronic hepatitis.
Alcoholic hepatitis
 Other liver
pathology

Chronic passive
congestion

Infarct Hemochromoatosis
PAS positive inclusions in hepatocytes
Cirrhosis
At the end of the course,
the students should be able to:

A. Identify the common lesions of the liver, biliary

system, gallbladder and pancreas
B. Recognize the pertinent lesions morphologically
(gross and microscopic findings)
C. Give the pathophysiology of the lesion
D. Correlate the clinical manifestations with the
pathology
Normal liver

Lobes of the liver:

• right lobe
– posterior caudate lobe
– anterior caudate lobe
• left lobe
Portal tract (PT) contains branches of the hepatic artery,
portal vein, and interlobular bile duct. The liver cell plates
converge to the terminal hepatic venule (THV).
 Diseases of the Liver
• Jaundice
• Hepatitis (acute/chronic)
• Fatty liver (Alcoholic Liver Disease)
• Cirrhosis
• Vascular disorders (portal
hypertension)
• Tumors (benign/malignant)
Jaundice
 Bilirubin
Metabolism
Causes of Jaundice
Causes of Jaundice
 Cholestasis
Intrahepatic: bile thrombi (B)
in dilated canaliculi,
predominantly in centrilobular
zones
Extrahepatic: Plugging of
biliary canaliculi; edema of portal
tracts (P); proliferation of small
bile ducts around the periphery of
portal tracts if long standing
Bile infarct of lakes (L) - caused
by hydropic degeneration of
hepatocytes associated with
leakage of bile from canaliculi
 Dubin Johnson syndrome

Pigment inclusions in otherwise normal hepatocytes

 Hepatitis:
• Acute hepatitis
• Chronic hepatitis
 • Hepatocytes swollen and vacuolated (“ballooning
degeneration”) (B)
Acute • Focal necrosis of hepatocytes (N), most severely affecting
Hepatitis • centrilobular areas of (Zone 3)
Cells dying by apoptosis seen as shrunken, eosinophilic
Councilman bodies (C)
 Hepatitis B: homogenous, pale, glassy
cytoplasm due to accumulation of HBsAg
Chronic
active
hepatiti
s

• Lymphocytic infiltrates in portal tracts (P) spills over into

adjacent parenchyma
• Piecemeal necrosis of liver cells (N) at the interface between
lobules and portal tracts, extending star-like, and later progresses
to bridging fibrosis between adjacent portal areas
Chronic persistent hepatitis

• Lymphoid infiltrates in portal tract

• No necrosis of limiting plate (P)
Hepatitis C
Early lobular hepatitis in HCV:
HCV progression into cirrhosis:
Fatty Liver
Alcoholic liver disease
Alcoholic liver disease
with Mallory bodies
Alcoholic Liver Disease
Alcoholic Hepatitis
 Micronodular cirrhotic
liver caused by alcohol
abuse

Macrovesicular
steatosis
Liver Cirrhosis
Macronodular
and
micronodular
cirrhosis
Primary biliary cirrhosis
 The major clinical
consequences of portal
hypertension in the
setting of cirrhosis
Patterns of Biliary Injury
 Biliary Atresia
• Lack of lumen in some part of the biliary
tree
• intrahepatic and extrahepatic
• morphologic features of neonatal hepatitis
Biliary atresia in a 3 mos. infant
 Pathophysiology of BA
• bile ducts differentiate from hepatocytes
• primary liver damage retards or prevents dev’t
of intrahepatic biliary passages.
• neonatal hepatitis, intrahepatic and extrahepatic
BA, ?choledochal cyst all result from common
inflammatory process,
Infantile Obstructive Cholangiopathy
 Extrahepatic Biliary Atresia
• obliteration of lumen of all or part of
extrahepatic biliary tree
• 50% of neonates with persistent
cholestasis
• 20% with other congenital anomalies
• may be associated with neonatal hepatitis
– chromosomal abnormalities (trisomies)
– viral infections
 Pathology of Extrahepatic BA:
• entire extrahepatic biliary tree or
restricted to segments of proximal or
distal biliary tree
• periluminal inflammation
• epithelial necrosis
• cellular debris in obstructed or narrowed
lumen
 Liver findings in EHBA:
• Cholestasis
• Multinucleated giant hepatocytes
• Periportal bile ductular proliferation

*hepatic bile ducts are gradually

obliterated
*secondary biliary cirrhosis supervenes
 Pathology of Intrahepatic BA:
• paucity of bile ducts or progressive loss of
intrahepatic bile ducts
• intralobular bile ducts to portal tracts ratio
is 0-0.4 (NV = 0.9 to 1.8)
• cholestasis
• giant cell transformation
• bile ductular proliferation
• cirrhosis occasionally encountered
Bile ductular proliferation 2o to cholestasis
 Intrahepatic Biliary Atresia
• paucity of bile ducts, no extrahepatic biliary
obstruction
• may be associated with:
– neonatal hepatitis (α1-antitrypsin deficiency;
chromosomal abnormalities; metabolic
derangement)
– Alagille syndrome (autosomal dominant
arteriohepatic dysplasia presenting as congenital
facial, cardiac, vertebral defects, etc.)
Neonatal Hepatitis
 Tumors of the Liver
• Benign tumor
– Adenoma
• Malignant tumor
– Hepatocellular carcinoma
– Cholangiocarcinoma
– Metastatic tumors
 Liver Cell Adenoma

Mass is composed of cords of hepatocytes without portal tracts.

Hepatocellular Carcinoma

Arrow points to
a satellite lesion
adjacent to the
massive tumor.
Hepatocellular Carcinoma
In well-differentiated
tumor, liver cells are
arranged as nests,
sometimes with central
lumen (arrow)
 Cholangiocarcinoma
Massive tumor with metastases;
tubular glandular structures in
densed sclerotic stroma.
 Metastatic tumors

Multiple masses from primary colon adenocarcinoma