GALL BLADDER from medicine pathology course

Gall bladder presentation

1. Gallbladder
Normal
Acute on chronic cholecystitis with
gallstone (arrow) & luminal pus

2. Outline: gallbladder disease
•Congenital lesion
•Gallstones: responsible >95% of biliary tract
diseases
•Tumors of the gallbladder: carcinoma

3. Congenital lesion
•Congenitally absent gallbladder
•Aberrant locations of the gallbladder
–5-10% of the population
–Partial or complete embedding in the liver
•Phrygian cap of the gallbladder
•Agenesis of bile ducts
•Extrahepatic biliary atresia
•Choledochal cyst: cystic dilatations of the biliary tree

4. Phrygian cap gallbaldder
Fundus of the gallbalder is
folded inward
The Phrygians were ancient Turks, around
1000 AD. They wore caps like this

5. Extrahepatic biliary atresia
•Complete or partial obstruction of extrahepatic biliary tree
within the 1
st
3 months of life
•Perinatal form: 80%, unknown cause, disease onset is after
birth
•Fetal form (aberrant development of the extrahepatic biliary
tree)
•Present with jaundice, dark urine, light or acholic stools, &
hepatomegaly
•Inflammation & fibrosis of the hepatic or common bile ducts
•Uncorrected => cirrhosis by 3-6months of age, death in 2yrs
•When surgical intervention is not feasible => Liver transplant

6. Biliary atresia
Absent gallbladder & fibrosis at the
porta hepatis
Portal edema, ductular reaction, and
neutrophil infiltrates Biliary cirhosis.
Biliary cirrhosis

7. Choledochal cyst
•Cystic dilatations of the biliary tree
•Extrahepatic or intrahepatic biliary
radicles, or both
•Most often in children <10yrs
•Jaundice &/or recurrent abdominal
pain, symptoms of biliary colic
•Predispose to stone formation,
stenosis & stricture, pancreatitis, &
obstructive biliary complications
within the liver; ↑ risk of
cholangiocarcinoma
Type I

8. Gallstones
•Cause significant morbidity WW
•10-20% of adult populations; 75-80% remain asymptomatic
–Low frequency of complications hence prophylactic
cholecystectomyisnot recommended
•Can form anywhere along the biliarytract, most commonly
in the gallbladder
•Composed ofcholesterol, bilirubin, calcium salts, & smaller
quantities of other constituents
•Cholelithiasisorgallstones refers to stones within the
gallbladder
•Choledocholithiasisrefers to gallstones within the bile ducts

9. Gallstones cont.
•Cholesterol & pigment type (black & brown)
•Strong female predilection
•Cholesterol typepredominate in theWestern countries
•Pigment type farmore common inAsia & Africa, associated
withchronic hemolysisorbiliary tract infections (bacterial or
parasitic)
Cholesterol stones

10. Risk Factors for Gallstones

11. Risk factors: cholelithiasis
•Rapid weight loss: enhanced hepatic secretion of
cholesterol, ↑ mucin production by gallbladder, & reduced
gallbladder motility
•Gallbladder stasis of neurogenic, hormonal, orinflammation
induced => ↑ formation of both cholesterol & pigment
stones
•1
st
degree relativesof patients with gallstones have2-to-4
fold higher riskof developing cholesterol gallstones
•Polymorphisms&mutationsin LITH genes =>
supersaturation of bile with cholesterol & conferhigh risk of
cholesterol gallstones

12. Pathogenesis of cholesterol stones
•Supersaturated bile with cholesterol
exceeds the solubilizing capacity of bile
=> cholesterol monohydrate crystals=>
macroscopic stones
•Summary:
Supersaturation of bile with cholesterol
Hypomotility of the gallbladder with bile
stasis
Cholesterol crystal nucleation
Hypersecretion of gallbladder mucins
that promote nucleation

13. Morphology: cholesterol stones
•Develop in the gallbladder
•~10% pure (100% cholesterol
monohydrate)
–Small or large, single or multiple, round to
ovoid, & pale to bright yellow in color
•Remainder are mixed stones: ~50%
cholesteroladmixed with calcium
bilirubinate& small amounts ofcalcium
carbonate&phosphate
–Small, multiple,faceted with darker cores
& a layered cut surface
•~80% radiolucent (lack calcium carbonate)
Pure
Mixed

14. Pathogenesis of pigment stones
•Excess of unconjugated bilirubin in the bile
•Any condition that ↑ the levels of unconjugated bilirubin
elevates the risk of pigment stone formation
•Both types are composed of insoluble calcium salts of
unconjugated bilirubinin a matrix ofmucin glycoproteins&
contain< 30% cholesterol

15. Pathogenesis of Black stones
•Arenot associated with biliary infections(sterile bile) &
usually form in gallbladder ofolder individuals
•Occur in ↑formation of bilirubin conjugates (e.g. chronic
hemolysis), ileal pathology (e.g. Crohn's disease), etc => ↑
unconjugated bilirubin in bile => calcium bilirubinate to form
stones

16. Pathogenesis of Brown stones
•Brown stones
•In infected (bacterial or parasitic) or obstructed bile ducts
•Microbial β-glucuronidaseshydrolyze bilirubin glucuronides
=>free bile acids&excess of unconjugated bilirubin
•Bacterialphospholipase A1degrades phospholipids to
formlysolecithin&free fatty acids(palmitic & stearic acids)
•Free bile acids & free fatty acids combine & precipitate
ascalcium saltswhich get trapped inglycoprotein gelto
form brown stones

17. Morphology of pigment stones
•Black stones
Multiple, <1.5 cm, 50-75%
are radiopaque (sufficient
Ca salts) visualized on plain
radiographs
Hard consistency, &
aredifficult to crush
between thumb & index
finger, unlike the brown
pigment stones
•Brown stones
Single or few in number,
larger, softer, lighter,
More fragilewith
anirregular, molded, or
spherical shape soapy or
greasy consistencyand
adull yellow-brown color
Radiolucent (calcium
soaps)

18. Pigment stones
Several faceted black gallstones are
present in this otherwise unremarkable
gallbladder from a patient with a
mechanical mitral valve prosthesis,
leading to chronic intravascular hemolysis

19. Clinical Features: gallstones & gallstone-
induced acute cholecystitis
•70-80% asymptomatic (shown by autopsy studies)
•Right upper quadrant pain or epigastric pain, often radiating
to the shoulder or back, with or withoutnausea&vomiting
•Abdominal pain/discomfort&flatulenceare often triggered
by afatty meal(inducesgallbladder contraction)

20. Ultrasound diagnosis of gallstones
This ultrasound shows two gallstones (arrow) within the gallbladder. The
stones are dependently located & show posterior acoustic shadowing.

21. Gallstones: complications
•Gallstones may obstruct cystic duct or distal bile duct:
Cystic duct => hydrops, mucocele, empyema of gallbladder
Obstructive jaundice, biliary-type pain
Acute cholecystitis, ascending cholangitisoracute biliary
pancreatitis
•Cholecystoenteric fistulasbetween gallbladder & duodenum
or colon (<0.1%)

22. Gallstones: complications
•Larger (> 2.5 cm) stones => small intestinal
obstructionresulting in gallstone ileus, &colonic or
appendiceal obstruction
•Gallbladder perforation => local abscess
•Gallbladder rupture => diffuse peritonitis
•Gallbladder carcinomain long-standing cholelithiasis (<0.1%)

23. Pathogenesis: acute calculous cholecystitis
•Chemical irritation & inflammation of a gallbladder
obstructed by stones
•Mucosal phospholipases hydrolyzes luminal lecithins to toxic
lysolecithins => disrupted glycoprotein mucous layer =>
detergent action of bile salts
•Prostaglandins => mucosal & mural inflammation
•Distention & ↑ed intraluminal pressure compromise blood
flow to the mucosa
•Later bacterial infection may be superimposed

24. Empyema of gallbladderHydrops of gallbladder
Acute on chronic cholecystitis&
gallstone (arrow)

25. Acute cholecystitis
•Acute calculous cholecystitis:
90%, obstruction of the gallbladder neck or cystic duct
•Acute acalculous cholecystitis (without gallstones):
10%, result from ischemia, risk factors: sepsis,
immunosuppression, severe trauma & burns, DM &
infection

26. Morphology: acute
cholecystitis
Enlarged, tense, & bright red,
violaceouscolor (subserosal
hemorrhages) Neutrophilsinfiltration & vascular
congestion of the mucosa of the
gallbladder

27. Chronic Cholecystitis
•In most instances it develops denovo (without any
antecedent acute attacks)
•Almost always (>90%) associated with gallstones
•Gallstones do not seem to be an essential part of the
initiation of inflammation or the development of pain
•Supersaturation of bile appears to predispose to both
chronic inflammation &, in most instances, stone formation
•Obstruction of gallbladder outflow is not a prerequisite

28. Chronic Cholecystitis cont.
•Morphology is extremely variable & sometimes minimal
•Recurrent attacks of epigastric or right upper quadrant pain,
nausea, vomiting, & intolerance for fatty foods
The gallbladder mucosa is
infiltrated by inflammatory cells.

29. Chronic cholecystitis: Rokitansky-Aschoff sinus
Outpouchingof the mucosal epithelium through the muscular wall of the
gallbladder (arrows)

30. Porcelain gallbladder
•The wall & surfaces of the gallbladder are hard & tan-white
like a porcelain vase
•Calcification due to chronic cholecystitis
•↑ risk for gallbladder cancer (1-6%)

31. Gallbladder with cholesterolosis
Strawberry Gallbladder
Numerous yellow dots against red-brown
mucosa in the background, somewhat
resembling a strawberry. In addition, there
is a small cholesterol polyp (arrow)
Expansion of a villous tip by numerous
macrophages with expanded foamy clear
cytoplasm

32. Cholesterolosis
•Incidental findingin the
gallbladder that is
characterized byaccumulation
of lipid-laden macrophagesin
themucosa
•Presence ofminute, yellow
linear flecksin a background
of green or congested
gallbladder mucosa creates
astrawberry-like appearance
Cholesterolosis: yellow linear flecks
runninglongitudinally scattered diffusely
throughout the gallbladder mucosa &
cholesterol gallstones

33. Gallbladder carcinoma
•Most common malignancy of the extrahepatic biliary tract
•F:M = 2:1, 6
th
& 7
th
decades
•Risk factors:
Cholelithiasis (major, 95%); 1-2% of patients with gallstones
develop gallbladder cancer
Chronic cholecystitis
Infections (esp.Salmonella&Opisthorchis viverrini) in Asia
Porcelain gallbladder
•Driver mutations: gain-of-function of EGF receptor gene
family (HER2), RAS & loss of function mutations in the TP53

34. Precursor lesions: gallbladder carcinoma
•Flat in situ lesions with varying degrees of dysplasia
•Intracholecystic papillary tubular neoplasm
•Intestinal metaplasia => dysplasia & carcinoma in situ

35. Gross morphology: gallbladder carcinoma
•Incidental gallbladder cancer in routine cholecystectomy
specimens can be grossly subtle (mucosal granularity or
irregularity, minimally raised or polypoid mucosal lesions or
focally thickened fundus or body)
•Frank tumors:
Infiltrating => thickened & indurated gallbladder wall
Exophytic or polypoid friable mucosal lesions (arising from
intracholecystic papillary neoplasm)
•Firm, gritty, tan-white to yellow-gray cut surface

36. Morphology: gallbladder adenoarcinoma
A) The opened gallbladder contains a large,
exophytic tumor (arrow) that virtually fills the
lumen
Infiltrating type: presenting as diffuse
thickening of the gallbladder wall

37. Morphology: gallbladder carcinoma
•Mainly are adenocarcinomas
•Most in the fundus (60%), body (30%) or neck (10%)
(B) Malignant glands are seen infiltrating a densely fibrotic gallbladder wall.

38. I
Incidental gallbladder adenocarcinoma detected
in a gallbladder with focal thickening
Well differentiated

39. Gall bladder
adenocarcinoma
•Direct extension into other
organs, fistula formation,
peritoneal & biliary spread
•Metastasis to the liver &
portahepatic lymph nodes
Advanced tumors: growing in diffuse fashion in the
distal wall of the gallbladder (G), associated with
extensive involvement of the liver (arrows)
*
G

40. Clinical Features: gallbladder carcinoma
•Asymptomatic in a large majority of patients
•Symptoms when present are vague; right upper quadrant
pain (most common), weight loss & fever
•Disease is usually advanced stage (invaded the liver with l.
node spread) by the time patient develops symptoms
•Mean 5 yr survival rate is <10%