Gallbladder and Biliary Tract Flashcards
T/F:
Gallbladder Wall: mucosa (lined by simple tall columnar, with goblet cell) muscularis, serosa/adventitia, NO SUBMUCOSA
True
Name the 3 extra hepatic biliary system
Extrahepatic biliary system:
cystic, common hepatic, common bile duct
Congenital anomalies of the Gallbladder
Duplication
Agenesis
Multiseptation
Phrygian cap deformity
DAMP
Agenesis of the gallbladder
T/F: usually no cystic duct and has no clinical significance
True
It is due to incomplete vacuolization of the developing gallbladder bud or persistent wrinkling of gallbladder wall
Multiseptate gallbladder
Multiseptate gallbladder are lined by
columnar epithelium
Septa causes what signs and symptoms?
impaired motility, stasis of bile flow, RUQ pain, nausea, vomiting
It is the inversion of distal fundus into the body
Phyrigian cap deformity
Treatment of correctable (10%) biliary atresia (patent proximal bile duct system)
Biliary-enteric anastomosis
Treatment of non-correctable (90%) biliary atresia (no patent portion of extrahepatic bile duct system that communicate with intrahepatic portion)
porto-enterostomy/ Kasai procedure (pallative) or liver transplantation (curative)
In biliary atresia, there is an increased deposition of what type of collagen in the basement membrane?
Type IV
T/F:
In biliary atresia, there is hyperplasia and hypertrophy of hepatic artery and branches
True
It is the dilatation of the CBD (some of intra and extra hepatic BD)
Choledochal cyst
T/F:
Choledochal cyst is associated with other hepatobiliary tract abnormality
True
T/F:
Choledochal cyst may rupture spontaneously causing acute abdomen
True
It is the common cause of obstructive jaundice in children beyond infancy
Choledochal cyst
2-8% develop biliary tract carcinoma within:
A. Within wall of cyst
B. Within gallbladder
C. Within bile ducts
D. AOTA
D. AOTA
There is lower risk if surgery is done early at age less than 10
Pathogenesis that can cause malignancy in this case is chronic inflammation
Type of choledochal cyst:
Segmental or diffuse fusiform dilation of common bile duct (50-90%)
Type 1
Type of choledochal cyst:
Diverticulum of the common bile duct
Type 2
Type of choledochal cyst:
Dilatation of intraduodenal common bile duct (choledochocele)
Type 3
Type of choledochal cyst:
multiple cyst of extrahepatic bile ducts with (4A) or without (4B) cysts of intrahepatic duct
Type 4
Type of choledochal cyst:
one or more cyst of intrahepatic ducts (Caroli’s disease)
Type 5
Microscopic appearance depends on age of patient at time of removal
On infant
intact epithelium , scanty inflammation
Microscopic appearance depends on age of patient at time of removal
On older children
more inflammation, epithelium discontinuous
Microscopic appearance depends on age of patient at time of removal
On adults
greater inflammation, destruction of epithelium, chronic cholecystitis, papillomas, adenocarcinomas
Heterotropic tissues are most common in
Gastric/ intestinal mucosa
It is a general term referring to stone in the biliary system without specific location
Cholelithiasis
It is a medical term for stone in the GB lumen
Cholecystolithiasis
It is a stone in the cystic duct
Choledocholithiasis
Pathogenesis of cholelithiasis
o Bile supersaturation with cholesterol
o Nucleation of cholesterol crystals: occur in the mucus gel of epithelial surface
o Precipitation of cholesterol monohydrate crystals
o Growth to stone-sized aggregates
Accumulation of Mucus gel, bile pigments, cholesterol that can be seen in UTZ prior to stone formation
Biliary sludge
Basic constituent of bile stone
o Cholesterol
o Calcium bilirubinate
o Calcium carbonate
T/F:
PURE GALLSTONE (10%)
o Only one of the above substrates
o Little or no inflammation if cystic duct not obstructed
True
Type of stone that is single, spheroidal, roughly nodular, translucent bluish white and most common in multiparous women
Cholesterol stones
T/F:
No correlation between cholesterol stone occurrence and level of blood cholesterol
True
T/F:
Cholesterol stones: women are twice at risk as much as men
True. Because there is hypersecretion of biliary cholesterol
T/F:
D19H variant: absorb less, synthesize more cholesterol (encoded by ABCG5 and ABCG2)
True.
Type of gallstone that is characterized by multiple, small, brown to black, faceted, 2-5mm in diameter, associated with cirrhosis, hemolytic disorders, artificial heart valves
Calcium bilirubinate stones
Type of gallstone that is characterized by amorphous, Grayish white, Powdery when broken
Calcium carbonate stones
Type of gallstones:
Various combinations of 3 basic constituents
Multiple. faceted, laminated (seen when broken)
Chronic cholecystitis: almost always preset
Mixed gallstones
Type of gallstone:
Large and single
Either: pure nucleus with mixed shell or reverse
Barrel stones: usually 2 in number, large, faceted on one side
Combined gallstones
Gallstones are formed where
Lumen of the gallbladder.
May go into cystic ducts or other extrahepatic ducts. They are NOT formed here, only transported
Choledocholithiasis: almost always secondary to cholecystolithiasis
cystic dilation of GB
Hydrops
An edema and compression common hepatic duct due to a travelling stone
Mirizzi syndrome
Linear yellow streaks in the prominences of the ridges surrounded by congested mucosa with reddish discolorations in between due to congestion is called
Strawberry gallbladder
Accumulated cholesterol in the lamina propria may grow and protrude into the lumen as a polypoid mass is called
Cholesterol polyps
Collections of lipid-laden foamy cells (macrophages) in the mucosal tips or in the lamina propria
Lipid laden macrophages are beneath the epithelium of the mucosa of the gallbladder
Inflammation: usually not significant, unless with stones in the cystic duct
Cholesterolosis
A gallbladder disease with the following most common manifestations:
RUQ pain, nausea and vomiting
Acute cholecystitis
primary complication of gallstones; MC reason for “E” (emergency) cholecystectomy
Acute calculous cholecystitis
T/F:
In acute cholecystitis, thre is presence of edema, congestion, hyperemia, extravasation of RBCs
Widespread fibroblastic proliferation
PMNs: usually none, except when there is CBD obstruction by a stone
Epithelium: marked reactive (proliferative) changes of mucosal epithelium
should not be interpreted as dysplastic change
True.
T/F:
It is not infectious; rather it is Chemical or ischemic
Nearly always related to stone impacted in cystic duct
Impaction: changes in the concentration and composition of bile, interference with venous supply of GB via obstruction of venous supply of GB via obstruction of venous channels around the cystic duct
True.
Chemical agents contributory to acute cholecystitis
trypsin (pancreatic juice), unconjugated bile salts, lysolecithin: leak through wall of GB to cause bile peritonitis
No stone involved
More common in children
May follow systemic infections typhoid fever, CMV, HIV)
(Strep septicaemia,
To histologically differentiates this, look for:
Greater degree of bi le infiltration of GB wall
More necrosis of muscle layer
Acute acalculous cholecystitis
MOST IMPORTANT RISK FACTOR IN CHRONIC CHOLECYSTITIS:
Presence of gallstone
Aggregates of foamy histiocytes in lamina propria covered by intact epithelium
Morphologic variation of cholesterolosis
No malignant potential
Cholesterol polyp
Patterns of growth of adenoma
Tubular
Tubulovillous (tubulopapillary)
Villous (papillary)
T/F:
Some degree of atypia often present (especially of the villous type)
True.
T/F
It is very rare for an adenoma to develop to a gallbladder malignancy
True
T/F:
Evidence of adenomas
Frequent expression of beta-catenin mutations (rare in Ca)
Lack of mutations in TP53 and P16 (tumor suppressor genes), KRAS (protooncogene) (frequent in cancer)
> 50% cases: (+) estrogen receptors: manifestation of metaplastic change in epithelium (and not neoplastic change)
True
MC AbN lab Finding in gallbladder malignancy
elevated Alkaline Phosphatase level
Initial event in the development of GB CA:
Inflammation
Gross:
Poorly defined area of diffuse thickening and induration of GB wall
More difficult to assess especially if there are recurrent bouts of chronic cholecystitis
Diffuse growing/infiltrating (70%)
GROSS:
Grows into lumen as an irregular, cauliflower mass
May neck underlying wall
Polypoid/exophytic (30%)
MC sites of involvement of gallbladder malignancy
neck or fundus
Well-formed glands with wide lumina lined by one to few rows of highly atypical cuboidal cells
Surrounding stroma: cellular, arranged concentrically
Characteristic: glands are well-differentiated at an architectural level but poorly differentiated at a cytologic level
Adenocarcinoma
Histochem, IHC, EM or adenocarcinoma
Mucin: sialomucin type (normal: sulfomucin/ sulfated mucin)
CK7+ / CK20 (cholangiocarcinoma: CK7+/CK20-)
EMA + (Epithelial Membrane Ag)
CEA + (Carcinoembryonic Ag)
AFP occasionally + (request if considering primary hepatic malignancy)
Electron Microscopy: Pleomorphic microvilli, mucin vacuoles, abundant lysosomes
Molecular Genetic Features:
Polymorphisms of:
Cyt P450 1A11, DNA repair genes, hormone-rel gene, inflammation genes, insulin sensitivity genes, lipid metabolism pathway genes
Molecular Genetic Features:
Accumulation of multiple genetic alterations:
Oncogenes, tumor suppressor genes, DNA repair genes
Molecular Genetic Features:
TP53 mutations (with overexpressed p53)
> 50% of cases; more in high grade tumors
Molecular Genetic Features:
KRAS (proto-oncogene) mutations
Associated with Ca with anomalous arrangement of pancreaticobiliary duct
(Best prognosis)
Predominant or exclusive papillary pattern
Papillary carcinoma
High grade
Very difficult to diagnose in light microscope
EM: Dense core secretory granules
Small cell neuroendocrine carcinoma
Adenoacanthoma (well – benign)
Adenosquamous CA (poor – malignant)
Squamous metaplasia
MC of GB carcinoma
Intestinal metaplasia, dysplasia, and CIS Biliary Intraepithelial Neoplasia)
T/F:
Spread and metastasis
Great propensity to directly invade liver
Also stomach and duodenum
Metastasis to liver (via portal tract), cystic and pericholedochal LN in lesser omentum, LN behind
the 1 st part of duodenum, aortocaval LN
True.
T/F:
Frequency of LN involvement:
Dependent on depth of invasion of primary tumor
True.
GB ➡️CD ➡️CBD ➡️LN posterior to 1 st part of duodenum and pancreatic head
Most common pathway
Cholecystoretropancreatic
GB ➡️gastrohepatic ligament ➡️celiac nodes
Cholecystoceliac
GB posterior to pancreas ➡️ aortocaval LN
Cholecystomesenteric
Prognostic Factor:
most important prognostic determinant
Stage
Prognostic Factor:
main determinant in early stage disease
Surgical margins
Prognostic Factor:
most favourable: well-differentiatd papillary adenocarcinoma
Grading
Prognostic Factor:
DNA content:
questionable
Prognostic Factor:
KRAS
(+) of codon 12 mutations is unfavourable
Prognostic Factor:
HER2 oncogene:
no correlation
Prognostic Factor:
Angiogenesis
(+) correlation
One of the complications of calculous cholecystitis
Due to stone impaction in the cystic duct
Cholangitis
Unknown etiology
Rare
Diffuse thickening of the wall
Lumen obstruction ➡️decreased lumen
Dense fibrosis
Sparse mixed inflammatory infiltrate
Intact epithelium
Sclerosing cholangitis
EARLY STAGES of sclerosing cholangitis
Best seen in the liver biopsy specimens
Fibrous obliterative cholangitis
Replacement of duct segments by fibrous cords of connective tissue
Leads to complete loss of bile ducts
DDX?
Biliary atresia
Sclerosing cholangitis has INCREASED INCIDENCE in patients with
HLA DRW52a antigen
Sclerosing cholangitis is ASSOCIATED with:
Riedel thyroiditis
Crohn disease
Ulcerative colitis: high frequency of serum anticolon antibodies
T/F:
The dysplastic changes can sometimes evolve to cholangiocarcinoma
True
Most common manifestation of cholangiocarcinoma
90%: jaundice (MC manifestation)
Since jaundice is the most common manifestation, a good differential would be your liver disease or liver CA
Cholangiocarcinoma has INCREASED INCIDENCE in:
Ulcerative colitis
Sclerosing cholangitis
Chronic infections with:
Clonorchis sinensis Vietnam) infection (Japan, Korea, Vietnam)
Opithorchis viveririni infection (Thailand, Laos, Malaysia)
Choledochal cysts, Caroli disease
Thorium dioxide (thorotrast) exposure: radiologic contrast dye used between 1930- 1950
T/F
Cholangiocarcinoma can develop in any level of the biliary trees
True.
Anatomical divisions:
Upper third: 50-75% (most proximal, nearest the liver)
Middle third: 10 -25 %
Lower third: (distal, nearest the duodenum) 10-20 %
Anatomic Classification by Bismuth:
What type?
below the confluence of right and Left hepatic ducts
Type 1
Anatomic Classification by Bismuth:
What type?
reaching the confluence
Type 2
Anatomic Classification by Bismuth:
What type?
occluding the common hepatic duct and either the right (IIIA) of left (IIIB) hepatic duct
Type 3
Anatomic Classification by Bismuth:
What type?
multi-centric, or involving the confluence and both the right and left hepatic ducts
Type 4
T/F:
Cholangiocarcinoma GROSS FEATURES:
May be Polypoid and superficial
Most are nodular or sclerosing with deeper penetration into the wall
Occasional: multi-centric accompanied by extensive intraepithelial component OR associated with GB carcinoma
Upper third lesions: direct extension to liver is common
Lower third lesions: extension into the pancreas
True.
Metastasis to regional lymph node: Frequent
o MC affected: those around lower portion of the hepatoduodenal ligament, superoposterior pacreaticoduodenal group and superior mesenteric artery group.
o AFP always positive for HCC and negative for CCA
T/F:
Cholangiocarcinoma MICROSCOPIC FEATURES:
MC: well differentiated, mucin secreting adenocarcinoma
Papillary Surface: more common in distal lesions
True.
Heterogeneity of cells within the same gland
Concentric layering neoplastic glands of cellular stroma around
Increase N:C ratio
Prominent nucleoli
Stromal and peri-neural invasion
*The best diagnostic tool is the first one and the last one
T/F:
(+) expression of muco-substances and CEA
(+) expression of CDX2 and MUC2: intestinal differentiation
Metaplastic and Dysplastic changes in adjacent epithelium
o this is more common in bile duct CA compared to gall bladder CA
IMMUNOHISTOCHEMISTRY
o Overexpression of p53
o Overexpression of DPC4 tumor suppressor gene implicated in genesis of pancreatic cancer this is more specific for bile duct CA
True.
a.k.a. Sclerosing carcinoma of the bile ducts
ALTEMEIER – KLATSKIN TUMOR
It mimics sclerosing cholangitis because of extensive necrosis, the difference is you see here neoplastic glands
Begins at hepatic duct junction
Spreads to long segments of the biliary tree
Long clinical course
Well differentiated microscopic appearance
Extensive fibrosis
DDx?
Sclerosing cholangitis
