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 duodenum is attached (A)
w/ intrapancreatic 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
•
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 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