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

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).

Acute Pancreatitis

1) chronic inflammation

2) fibrous scarring

3) loss of parenchymal elements

4) duct strictures & ectasia

w/ intrapancreatic calculi formation

Chronic Pancreatitis

Atrophic pancreas (P) replaced by rubbery, fibrous tissue. Ducts are dilated (D), the duodenum is attached (A)

Carcinoma of the Pancreas: 99% adenoCADistribution: 60% head; 20% diffuse; 10% body; 10% tailRisk factors: cigarette smoking; high fat/meat intake; hx of gastrectomy/pancreatitis

Pancreatic duct adenocarcinoma:

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

CholestasisIntrahepatic: 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

Acute Hepatitis

• Hepatocytes swollen and vacuolated (“ballooning degeneration”) (B)

• Focal necrosis of hepatocytes (N), most severely affecting 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

hepatitis

• 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 (1-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