patoloji-ders-notlari

Title

Serdar Balcı

Gallbladder and Extrahepatic Biliary Tract Diseases

Serdar BALCI, MD

GALLBLADDER DISEASES

Congenital Anomalies

Agenesis

Duplication

Bilobed gallbladder

Aberrant location

Phrygian cap of the gallbladder

Fundus is folded inward.

Cholelithiasis (Gallstones)

• 10-20% of adults in Western countries in the Northern Hemisphere
• 20-40% in Latin American countries
• 3-4% in Asian countries
• Cholesterol stones
  • Containing crystalline cholesterol monohydrate
  • 80% of stones in the West
• Pigment stones
  • Made of bilirubin calcium salts
• Bile formation
  • Only significant pathway for elimination of excess cholesterol from the body
  • Either as free cholesterol or as bile salts
• Cholesterol
  • Water-soluble by aggregation with bile salts and lecithins
  • Concentrations exceed the solubilizing capacity of bile (supersaturation)
  • Remain dispersed and crystallizes out of solution

• Gallstone formation
  • Enhanced by hypomobility of the gallbladder (stasis)
  • Promotes nucleation
  • Mucus hypersecretion
  • Consequent trapping of the crystals
  • Aggregation into stones
• Precipitates are primarily insoluble calcium bilirubinate salts

Risk Factors for Cholelithiasis

• 80% no identifiable risk factors other than age and gender
• Prevalence increases throughout life
• F:M = 2:1
• 50-75% in certain Native American populations
  • Related to biliary cholesterol hypersecretion
• Positive family history increases risk
  • Errors of metabolism, impaired bile salt synthesis and secretion
• Estrogenic influences
  • Oral contraceptives and pregnancy, increase hepatic cholesterol uptake and synthesis
• Obesity, rapid weight loss, hypocholesterolemic agent clofibrate
  • Increased biliary cholesterol secretion
• Gallbladder motility is reduced
  • Pregnancy, rapid weight loss, spinal cord injury
  • Without obvious cause

Robbins Basic Pathology

Cholesterol gallstones

Robbins Basic Pathology

Cholesterol stones

Most common in gallbladder

50-100% cholesterol

Pale

Increasing proportions of calcium carbonate, phosphates, and bilirubin impart gray-white to black discoloration

Ovoid and firm

Can occur singly

Several, with faceted surfaces resulting from their apposition

Most radiolucent, 20% sufficient calcium carbonate to be radiopaque

Autopsy Pathology: A Manual and Atlas

Pigmented gallstones

Robbins Basic Pathology

Pigment stones

• Anywhere in the biliary tree
• Lesser amounts of other calcium salts, mucin glycoproteins, and cholesterol
• Hemolytic anemias and infections of the biliary tract
• Black stones
  • Sterile gallbladder bile
  • Small in size, fragile to the touch, and numerous
  • 50% to 75% of black stones are radiopaque
    • calcium carbonates and phosphates
• Brown stones
  • Infected intrahepatic or extrahepatic ducts
  • Single or few in number
  • Soft, greasy, soaplike consistency
    • retained fatty acid salts released by the action of bacterial phospholipases on biliary lecithins
  • Radiolucent
    • calcium soaps

Cholelithiasis (Gallstones)

• 70-80% asymptomatic throughout life
• pain, often excruciating
  • right upper quadrant or epigastric region
  • constant or, less commonly, spasmodic
  • “biliary” pain is caused by gallbladder or biliary tree obstruction, or by inflammation of the gallbladder itself
• empyema, perforation, fistulas, inflammation of the biliary tree, and obstructive cholestasis or pancreatitis
• The larger the calculi, the less likely they are to enter the cystic or common ducts to produce obstruction
  • small stones, or “gravel,” are more dangerous
  • A large stone may erode directly into an adjacent loop of small bowel, generating intestinal obstruction ( gallstone ileus )

Cholesterolosis in gallbladder

Autopsy Pathology: A Manual and Atlas

Cholesterolosis in gallbladder

Cholecystitis

• Inflammation of the gallbladder
• Acute, chronic, or acute superimposed on chronic
• Almost always occurs in association with gallstones
  • epidemiologic distribution closely parallels that of gallstones

Acute cholecystitis

• Gallbladder usually is enlarged and tense
• A bright red or blotchy, violaceous color
  • subserosal hemorrhages
• Frequently covered by a fibrinous, fibrinopurulent exudate
• 90% of cases, stones are present
  • obstructing the neck of the gallbladder or the cystic duct
• Lumen
  • filled with cloudy or turbid bile
  • contain fibrin, blood, and frank pus
  • exudate is mostly pus
    • empyema of the gallbladder
• Wall
  • thickened, edematous, and hyperemic
  • **green-black necrotic **
    • gangrenous cholecystitis
• Histologic examination:
  • Edema
  • Leukocytic infiltration
  • Vascular congestion
  • Frank abscess formation
  • Gangrenous necrosis

Acute Calculous Cholecystitis

Acute inflammation of a gallbladder with stones

Obstruction of the gallbladder neck or cystic duct

Most common major complication of gallstones

Most common reason for emergency cholecystectomy

• Chemical irritation and inflammation of the gallbladder wall

• Phospholipases derived from the mucosa

  • hydrolyzes biliary lecithin to lysolecithin
  • toxic to the mucosa

• Protective glycoprotein mucous layer is disrupted

  • mucosal epithelium direct contact with detergent action of bile salts

• Prostaglandins released within wall of the distended gallbladder

  • contribute to mucosal and mural inflammation

• Distention and increased intraluminal pressure

  • compromise blood flow to the mucosa

• Later bacterial contamination may develop

• 5-12% contain no gallstones

• occur in seriously ill patients

  • Major, nonbiliary surgery
  • Severe trauma (e.g., from motor vehicle crashes)
  • Severe burns
  • Sepsis

• Dehydration, gallbladder stasis and sludging, vascular compromise, bacterial contamination

Chronic Cholecystitis

Changes are sometimes subtle

Presence of stones within the gallbladder

Absence of acute inflammation

Contracted, of normal size, or enlarged

Mucosal ulcerations are infrequent

Submucosa and subserosa often are thickened from fibrosis

mural lymphocytes

• sequel to repeated bouts of acute cholecystitis
• without any history of acute attacks
• Almost always associated with gallstones
  • gallstones do not seem to have a direct role in the initiation of inflammation or the development of pain
  • chronic acalculous cholecystitis causes symptoms and morphologic alterations similar to those seen in the calculous form
• Supersaturation of bile
  • chronic inflammation
  • stone formation
• Microorganisms
  • E.coli and enterococci
  • cultured from the bile in only about one third of cases
• Complications:
  • Bacterial superinfection with cholangitis or sepsis
  • Gallbladder perforation and local abscess formation
  • Gallbladder rupture with diffuse peritonitis
  • Biliary enteric (cholecystenteric) fistula
    • drainage of bile into adjacent organs
    • entry of air and bacteria into the biliary tree
    • gallstone-induced intestinal obstruction (ileus)
  • Aggravation of preexisting medical illness
    • cardiac, pulmonary, renal, or liver decompensation

Robbins and Cotran Pathologic Basis of Diseases

Robbins and Cotran Pathologic Basis of Diseases

DISORDERS OF EXTRAHEPATIC BILE DUCTS

Choledocholithiasis

• Choledocholithiasis and Cholangitis frequently occur together
• Choledocholithiasis
  • presence of stones within the biliary tree
  • Western nations, almost all stones are derived from the gallbladder
  • Asia, much higher incidence of primary ductal and intrahepatic, pigmented, stone
  • may not immediately obstruct major bile ducts
  • asymptomatic stones are found in about 10% of patients at the time of surgical cholecystectomy

Symptoms may occur:

Biliary obstruction

Cholangitis

Hepatic abscess

Chronic liver disease with secondary biliary cirrhosis

Acute calculous cholecystitis

Cholangitis

• Acute inflammation of the wall of bile ducts

• Almost always caused by bacterial infection of the normally sterile lumen

• Result from any lesion obstructing bile flow

  • most commonly choledocholithiasis
  • surgery involving the biliary tree
  • Tumors
  • indwelling stents or catheters
  • acute pancreatitis
  • benign strictures

• May lead to cholestasis and more importantly sepsis

• Ascending cholangitis

  • Bacteria enter the biliary tract through the sphincter of Oddi
  • once within the biliary tree, infection goes to intrahepatic biliary ducts
  • E. coli, Klebsiella, Enterococci, Clostridium, and Bacteroides
  • Two or more organisms are found in half of the cases

• Parasitic cholangitis

  • Fasciola hepatica or schistosomiasis in Latin America and the Near East
  • Clonorchis sinensis or Opisthorchis viverrini in the Far East
  • Cryptosporidiosis in persons with AIDS

• Suppurative cholangitis

  • purulent bile fills and distends bile ducts
  • risk of liver abscess formation

Secondary Biliary Cirrhosis

• Prolonged obstruction of the extrahepatic biliary tree may cause damage to the liver
  • Extrahepatic cholelithiasis
    • most common cause
  • Biliary atresia
  • Malignancies of the biliary tree and head of the pancreas
  • Strictures resulting from previous surgical procedures
• Initially → cholestasis
  • entirely reversible with correction of the obstruction
• Secondary inflammation → initiates periportal fibrogenesis
  • leads to scarring and nodule formation
  • generating secondary biliary cirrhosis

Biliary Atresia

Major cause of neonatal cholestasis

One third of the cases of cholestasis in infants

1 in 10,000 live births

Complete obstruction of bile flow

destruction or absence of all or part of the extrahepatic bile ducts

most frequent cause of death from liver disease in early childhood

more than half of the referrals of children for liver transplantation

Features of biliary atresia

• Inflammation and fibrosing stricture of the hepatic or common bile ducts
• Inflammation of major intrahepatic bile ducts, with progressive destruction of the intrahepatic biliary tree
• Florid features of biliary obstruction on liver biopsy
  • ductular reaction, portal tract edema and fibrosis, and parenchymal cholestasis
• Periportal fibrosis and cirrhosis within 3 to 6 months of birth

TUMORS

Carcinoma of the Gallbladder

• Most frequent malignant tumor of the biliary tract

• 2-6x common in women

• Most frequently in the seventh decade of life

• More frequent in the populations of Mexico and Chile

  • higher incidence of gallstone disease in these regions

• Rarely is it discovered at a resectable stage

• Mean 5-year survival rate is 5%

• Gallstones present in 60-90% of cases

• In Asia, where pyogenic and parasitic diseases of the biliary tree are more common, gallstones are less important

• Gallbladders containing stones or infectious agents develop cancer as a result of recurrent trauma and chronic inflammation

• The role of carcinogenic derivatives of bile acids is unclear

• Infiltrating growth patterns

  • more common
  • poorly defined area of diffuse thickening
  • induration of the gallbladder wall
  • may cover several square centimeters or involve the entire gallbladder
  • scirrhous and very firm

• Exophytic growth pattern

  • grows into the lumen as an irregular, cauliflower-like mass but at the same time also invades the underlying wall

• Adenocarcinomas

  • papillary or poorly differentiated

• 5% are squamous cell carcinomas or demonstrate adenosquamous differentiation

• Rare neuroendocrine tumors

• By the time gallbladder cancers are discovered, most have invaded the liver or have spread to the bile ducts or to the portal hepatic lymph nodes

• Preoperative diagnosis <20%

Robbins Basic Pathology

Robbins and Cotran Pathologic Basis of Diseases

__ WHO Classification of Tumours of the Digestive System__

Intracholecystic Papillary Tubular Neoplasm of the

Gallbladder With Microinvasive Carcinoma

Pathol Case Rev 2014;19: 283 – 288

Cholangiocarcinomas

• Adenocarcinomas
• Arise from cholangiocytes lining the intrahepatic and extrahepatic biliary ducts
• Papillary or flat precursor lesions
• Extrahepatic cholangiocarcinomas
• 2/3 of cholangiocarcinomas
• Develop at the hilum
  • Klatskin tumors
• More distally in the biliary tree
• 50-70 years of age

Both intra- and extrahepatic cholangiocarcinomas generally are asymptomatic until they reach an advanced stage

Prognosis is poor

Most patients have unresectable tumors

• Risk factors include chronic cholestasis and inflammation
  • Primary sclerosing cholangitis
  • Fibropolycystic diseases of the biliary tree
  • Infestation by Clonorchis sinensis or Opisthorchis viverrini
• Activating mutations in the KRAS and BRAF oncogenes and loss-of-function mutations in the TP53 tumor suppressor gene

Cholangiocarcinoma

Massive neoplasm in the right lobe and widespread intrahepatic metastases.

Robbins Basic Pathology

Robbins and Cotran Pathologic Basis of Diseases

Robbins Basic Pathology

Robbins and Cotran Pathologic Basis of Diseases

Robbins and Cotran Pathologic Basis of Diseases

• Extrahepatic biliary tumors tend to be relatively small at the time of diagnosis
  • cause obstruction and symptoms
• Intrahepatic tumors may cause symptoms only when much of the liver is replaced by tumor
• Spread to extrahepatic sites
  • regional lymph nodes, lungs, bones, and adrenal glands
  • Invasion along peribiliary nerves to spread to the abdomen
• Cholangiocarcinoma has a greater propensity for extrahepatic spread than does hepatocellular carcinoma

Autopsy Pathology: A Manual and Atlas

Autopsy Pathology: A Manual and Atlas

Autopsy Pathology: A Manual and Atlas

Autopsy Pathology: A Manual and Atlas

Autopsy Pathology: A Manual and Atlas

Autopsy Pathology: A Manual and Atlas