1. Department of Pathology
Biliary Tract
Kimiko Suzue MD, Ph.D.
Department of Pathology

2. Biliary Tract Extrahepatic biliary tract Intrahepatic biliary tract
Gallbladder
Cystic duct
Common hepatic duct
Common bile duct
Intrahepatic biliary tract

3. Biliary Disease Gallbladder Disorders Extrahepatic Bile Duct Disorders
-Cholelithiasis
-Cholesterolosis
-Cholecystitis
Extrahepatic Bile Duct Disorders
-Choledocholithiasis
-Cholangitis
-Biliary Atresia
-Choledochal cysts
Tumors

4. GALLBLADDER Contraction of the muscle induced by cholecystokinin
Storage and concentration of bile

5. Gallbladder Gallstones (cholelithiasis)
Afflict 10% of adult population in Western countries
Costs of management: $6 billion a year
20 million patients are estimated to have gallstones totalling several tons
Made of cholesterol, bilirubin and calcium salts with different concentrations

6. Cholelithiasis In West, >90% are cholesterol stones
Usually radiolucent (10% radiopaque due to calcium)
Risk factors:
-Native Americans
-Women > Men
-Advancing Age (25-30% of people over 80)
-Estrogenic influence
Pregnancy, Oral contraceptives
-Clofibrate
-Obesity
-Gallbladder stasis (neurogenic or hormonal)
-Hereditary (bile acid metabolism)

8. Cholelithiasis Pigmented bilirubin stones
Usually radiopaque (calcium bilirubinate)
Risk factors:
-Chronic hemolytic states (increased bilirubin in bile)
Sickle cell, hereditary spherocytosis, cardiac valve replacement, malaria)
-Ileal disease (bile salt malabsorption)
Crohn’s disease, bowel resection
-Biliary tract infection/infestation
Ascaris lumbricoides, Clonorchis sinensis
-Liver disease (alcoholic cirrhosis)

10. Cholelithiasis
Hepatolithiasis
Choledocholithiasis

11. Cholelithiasis Asymptomatic: 70% Obstruction: Biliary Colic
Spasmodic right upper quadrant pain
Symptoms are relieved if stone passes
Infection: Cholecystitis, cholangitis
Acute Pancreatitis
Gallbladder cancer
Principal therapeutic modality:
Laporascopic cholecystectomy (late 1980’s)

12. Cholesterolosis
Aggregates of lipid-containing macrophages in lamina propria of gallbladder
Debated clinical relevance
“Strawberry gallbladder”

13. Cholesterolosis

14. Polypoid cholesterolosis
Abundant foamy macrophages forming polypoid excrescences

15. Cholecystitis General Features
Present in autopsy series in half of the population
Female, obese, multiparous, 5th and 6th decades
Acute (Chemical irritation and inflammation)
Suppurative (Empyema, purulent contents)
Emphysematous (clostridia and coliforms)
Gangrenous (Necrotic)
Chronic

16. Cholecystitis Clinical Picture
Acute:
RUQ pain referred to right shoulder
Rigidity of abdominal wall (RUQ)
Fever, nausea, vomiting, leukocytosis
Jaundice (25% of cases)
Increased WBC count
Increased serum alkaline phosphatase (duct damage)
Chronic:
Fatty food intolerance
Epigastric distress, nausea
Vague RUQ pain
Complications: Ca or obstructive jaundice

17. Acute Cholecystitis Gross Pathology
The gallbladder is enlarged (x2 or x3)
The gallbladder wall is thickened (x10)
The serosa is covered by fibrin with subserosal hemorrhages
The lumen is filled with turbid bile, fibrin or pus
The mucosa is hyperemic, ulcerated or frankly necrotic
Gallstones are present in 80% of cases

19. Acute Cholecystitis Histology
Edema and neutrophilic inflammation
Vascular congestion
Abscess formation & gangrenous necrosis
Later neutrophils → eosinophils (subacute)
Ca++ deposition: “porcelain gallbladder”

20. Porcelain Gallbladder

21. Porcelain Gallbladder with Stones

23. Chronic Cholecystitis Gross Pathology
The gallbladder wall thickened (about x5)
It is contracted, enlarged or of normal size
Serosa is smooth and glistening with subserosal fibrosis
Lumen contains normal bile
Stones are present in 90% of cases

24. Chronic Cholecystitis Histology
Mucosa is preserved or atrophic
Mononuclear cell infiltration
Subepithelial and subserosal fibrosis
Severe fibrosis with replacement of smooth muscle
Outpouchings of mucosal epithelium through wall “Rokitansky-Aschoff sinuses”

28. Choledocholithiasis
Passage of gallstones into common bile duct occurs in 10-15% of patients with cholelithiasis
Majority are cholesterol stones formed in gallbladder
Primary calculi arising de novo in ducts are typically pigmented stones in pts with:
-Chronic recurrent cholangitis
-Congenital anomalies of bile ducts (Caroli’s disease)
-Dilated, sclerosed or strictured ducts
-MDR3 gene defect leading to impaired biliary phospholipid secretion

29. Choledocholithiasis May remain asymptomatic
May pass spontaneously into duodenum
May present as biliary colic or complications
-Cholangitis
-Obstructive jaundice
-Pancreatitis
-Secondary biliary cirrhosis

30. Cholangitis Acute or chronic
Bacteria present in 75% of pts with acute cholangitis
Charcot’s triad
Intermittent abdominal pain
Spiking fevers with chills
Jaundice

31. Biliary Atresia
Complete or partial obstruction of lumen of extrahepatic biliary tree within first 3 months of life
Perinatal type (80% to >90%)
-Presumed normal biliary tree is destroyed at birth
-Jaundice develops within 2 weeks
-No associated congenital anomalies
-Etiology unknown(?viral, ?autoimmunity)
Fetal type (less common)
-Jaundice at birth or within a day or 2
-Assoc cardiac and vascular malformations, sinus inversus, polysplenia, midgut malrotation
-Presumed aberrant intrauterine development of extrahepatic biliary tree

32. Biliary Aresia Histologic features: Bile ductular proliferation
Portal fibrosis
Bile plugs in bile ducts/ductules
Parenchymal cholestasis

33. Biliary Atresia Type I – Disease limited to common bile duct
Type II – Disease limited to hepatic bile ducts
Type III – Obstruction of ducts above porta hepatis

34. Biliary Atresia Normal birth weight and postnatal weight gain
Initially normal stools but become acholic stools
Present with neonatal cholestasis
Timing of biopsy
Liver biopsy shows nonspecific changes at less than 4 weeks
Fairly good sensitivity/specificity at 6-8 weeks
Diagnostic at >8 weeks
Cirrhosis develops within 3 to 6 months if not recognized
Kasai procedure for types I and II
Liver transplantation for rest
Without surgery, death within 2 years

35. Choledochal Cysts
Congenital dilatations of bile duct

36. Choledochal Cysts Present most often before 10 yrs of age
Jaundice, abdominal pain, abdominal mass
Delayed diagnosis can lead to complications:
Pancreatitis
Spontaneous perforation
Cholelithiasis
Cholangitis
Secondary biliary cirrhosis
Portal hypertension
Carcinoma

37. Carcinoma of Gallbladder
Close to 50% of gallbladder carcinomas are diagnosed incidentally in cholecystectomy specimens for cholelithiasis
Most important risk factor is cholelithiasis
-Gallstones present in >80% of gallbladders with carcinomas
-But low incidence of carcinoma in pts with gallstones, <0.2%
Slightly more common in women
Most frequent in seventh decade of life
Mean 5 year survival of 5 to 12%

38. Carcinoma of the Gallbladder Clinical Symptoms
Pain %
Weight loss 60%
Jaundice 50%
Gallstones %
Palpable mass 60%
Ascites %

39. Carcinoma of the Gallbladder Histologic Types
Adenocarcinoma
Adenosquamous carcinoma
Squamous cell carcinoma
Intracystic or intraductal papillary neoplasm with an associated invasive carcinoma
Mucinous cystic neoplasm with an associated invasive carcinoma
Undifferentiated carcinoma
Neuroendocrine neoplasms
Mesenchymal tumors

40. Dysplasia

41. Adenoca. of Gallbladder

42. Adenoca of Gallbladder

43. Adenoca of Gallbladder

44. Adenoca of Gallbladder

45. Biliary Disease Gallbladder Disorders Extrahepatic Bile Duct Disorders
-Cholelithiasis
-Cholesterolosis
-Cholecystitis
Extrahepatic Bile Duct Disorders
-Choledocholithiasis
-Cholangitis
-Biliary Atresia
-Choledochal cysts
Tumors