Gallbladder and extrahepatic bile ducts
Last revised 8 July 2008
Last major update May 2004
Copyright (c) 2004-2008, PathologyOutlines.com, Inc.
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Gallbladder
Normal anatomy, normal histology, embryology, normal physiology
Congenital anomalies: abnormal position, agenesis, cysts, diverticula, heterotopia, hourglass gallbladder, hypoplasia, micro gallbladder, multiseptate gallbladder, Phrygian cap, wandering gallbladder
Cholecystitis: acute, chronic, AIDS-related, emphysematous, eosinophilic, follicular, gangrenous, granulomatous, malakoplakia, porcelain gallbladder, xanthogranulomatous
Miscellaneous non-tumor: adenomyomatous hyperplasia, choledocholithiasis, cholelithiasis, cholesterolosis, fistula, gallbladder in extrahepatic bile duct obstruction, gallstone classification, gallstone ileus, hydrops / mucocele, metaplasia, papillary hyperplasia, vasculitis
Benign gallbladder tumors: adenoma, adenomyosis, cholesterol polyp, granular cell tumor, hyperplastic/metaplastic polyp, inflammatory polyp, villous papilloma
Dysplasia: general, dysplasia-carcinoma sequence
Malignant gallbladder tumors: gallbladder carcinoma, carcinoma in situ, clear cell carcinoid, Ewings/PNET, gastrointestinal stromal tumor, large cell neuroendocrine carcinoma, metastases to gallbladder, mucinous tumor, sarcomatoid carcinoma, small cell carcinoma, squamous cell carcinoma
Miscellaneous: TNM staging for gallbladder carcinoma, frozen section, grossing, features to report
Extrahepatic bile ducts
Normal anatomy, normal histology, metaplasia
Congenital anomalies: choledochal cyst, extrahepatic biliary atresia, primary sclerosing cholangitis, secondary sclerosing cholangitis
Tumors: adenoma, carcinoid, carcinoma, cystadenoma, dysplasia, granular cell tumor, intraductal papillary neoplasms, metastases, neurofibroma, papillomatosis, rhabdomyosarcoma, traumatic neuroma
TNM staging for extrahepatic bile duct carcinoma, features to report
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), January 1999 to May 2004
Archives of Pathology and Laboratory Medicine (Archives), January 1999 to May 2004
Human Pathology, Jan 1999 to May 2004
Modern Pathology, Jan 1999 to May 2004
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
Review articles: Radiographics 2002;22:387
Search terms: gallbladder, extrahepatic bile duct
Please refer to these primary references for more detailed discussions and photographs
Gallbladder
Pear shaped saccular structure for bile storage in gallbladder fossa of posterior right hepatic lobe
10 x 4 cm, but depends on volume of bile (normal 40-70 ml)
Wall thickness 1-2 mm
Has fundus, body and neck
Distal fundus: extends beyond anterior liver margin
Central body: most of gallbladder
Neck: narrows as it joins the cystic duct
Infundibulum: portion of body that joins the neck
Hartmann’s pouch: dilation in infundibulum, may be due to chronic inflammation
Vasculature: supplied by cystic artery, usually a branch of right hepatic artery
Note: variations of bile ducts and arteries may be dangerous during surgery
Regional lymph nodes: lymph node present at gallbladder neck or cystic duct drains to hepatic hilar nodes (along common bile duct, hepatic artery, portal vein, cystic duct); also celiac, periduodenal, peripancreatic and superior mesenteric nodes
Gross images: opened, relationship to liver #1, #2
Normal histology-Gallbladder
Has mucosa, muscularis propria and serosa on free surface; no muscularis mucosa or submucosa is present
Mucosa: variable branching folds, more prominent if gallbladder not distended
Surface epithelium: composed of single layer of uniform, tall columnar cells with basal nuclei, indistinct nucleoli, pale cytoplasm due to sulfomucins; also pencil cells (small, darkly staining columnar cells), inconspicuous basal epithelial cells, T lymphocytes; no goblet cells, myoepithelial cells or melanocytes; neck region has tubuloalveolar mucus glands that secrete sulfo-, sialo- and neutral mucin and contain neuroendocrine cells; true glands are not present outside the neck
Lamina propria: loose connective tissue with blood vessels, lymphatics, occasional chronic inflammatory cells (IgA secreting plasma cells), no neutrophils
Muscular layer: circular, longitudinal and oblique smooth muscle fibers without distinct layers, resembles muscularis mucosa; adjacent to lamina propria without an intervening submucosa
Adventitia: perimuscular connective tissue composed of collagen, elastic tissue, fat, vessels, lymphatics, nerves, paraganglia
Peritoneum: lines gallbladder that is not directly attached to liver, is continuous with that of liver
Aberrant bile ducts (ducts of Lushka): present in 10% of cholecystectomy specimens, often buried in gallbladder wall adjacent to liver, may contain collar of fibrous tissue, may communicate with intrahepatic bile ducts
Rokitansky-Aschoff sinuses: outpouchings of gallbladder mucosa that penetrate into muscle wall; may be acquired herniations
Larger accessory bile ducts: join with cystic or hepatic ducts, may be present within gallbladder bed
Mucin-secreting accessory glands: prominent near terminus of common bile duct
Micro images: cross section #1, #2, #3, #4
Virtual slides: normal gallbladder
Positive stains (surface epithelium): EMA, low molecular weight keratin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, polyclonal CEA
Develops with bile duct and liver during week 4 as ventral bud (hepatic diverticulum) from caudal foregut
Hepatic diverticulum has two components: pars hepatica and pars cystica
Parts hepatica gives rise to liver, common hepatic duct and intrahepatic bile ducts
Pars cystica gives rise to cystic diverticulum, which gives rise to gallbladder and cystic duct
Hepatic diverticulum elongates to form common bile duct
Above structures begin as solid cords, but at 8 weeks have lumina
Drawings: embryology
Bile excretion is normally 500-1000 ml/day
Bile is concentrated 5-10x via active absorption of electrolytes accompanied by passive movement of water
Cholecystokinin causes gallbladder contraction and release of stored bile into gut
Bile is critical for intestinal absorption of dietary fat, but the gallbladder is not
Bile is 2/3 bile salts, bicarbonate rich, has 3% organic solutes
Bile salts: cholates, chenodeoxycholates, deoxycholates, lithocholates, ursodeoxycholates; major hepatic products of cholesterol metabolism; a family of water-soluble sterols with carboxylated side chains; are highly effective detergents, solubilize water-insoluble lipids secreted by the liver (usually lecithin) into the biliary tree and promote dietary lipid absorption within the gut
Lecithin (phosphatidylcholine): hydrophobic, non-aqueous; has minimal solubility in water
95% of secreted bile salts is reabsorbed in ileum and returned to liver via portal blood, called enterohepatic circulation of bile salts
Cholesterol is eliminated by loss of 0.5 g of bile salts per day
Congenital anomalies-Gallbladder
Includes duplication, bilobed gallbladder due to longitudinal or transverse septum, agenesis of hepatic or common bile duct, hypoplastic narrowing of biliary channels (true biliary atresia), and topics below
Rare
Left sided (with or without situs inversus), intrahepatic (5%), retroperitoneal, suprahepatic; also within falciform ligament, lesser sac or abdominal wall
Rare; 50% discovered at autopsy
Usually no cystic duct either
Associated with choledocholithiasis, duodenal atresia and other congenital anomalies
No clinical significance
May begin as pseudodiverticula (Rokitansky-Aschoff sinuses) with progressive occlusion of communication with gallbladder
Solitary, 6 mm to 8 cm
Rarely are congenital anomalies with all 3 layers of gallbladder wall
Usually pseudodiverticula (Rokitansky-Aschoff sinuses) with incomplete muscular wall; due to cholelithiasis or cholecystitis
Also called ectopia or choristoma
Normal tissue in abnormal location
Usually incidental
Includes liver parenchymal nodules, usually 2.5 cm or less, suspended to gallbladder by mesenteric stalk (DD: accessory lobe); gastric heterotopia arising as intramural nodules, plaques or polyps, in neck or cystic duct, rarely with peptic ulceration; pancreatic heterotopia with acinar tissue, rarely islets, that may cause acute pancreatitis in gallbladder
Micro images: gastric heterotopia #1, #2, pancreas heterotopia of common bile duct
Divided by central constriction
Variant of transverse septate gallbladder
Usually acquired, due to septum of inflamed fibrous tissue or adenomyomatous hyperplasia
Associated with extrahepatic biliary atresia
Micro: compressed epithelium-lined structures, fibrous tissue, smooth muscle strands, inflammatory cells in gallbladder fossa and porta hepatis
Defined as less than 2-3 cm long, 0.5 -1.5 cm wide
Associated with idiopathic neonatal hepatitis, alpha-1-antitrypsin disease, cystic fibrosis
Congenital or acquired
3-10 communicating compartments lined by columnar epithelium
Stones often present in adults
Inversion of distal fundus into body, to which it may become adherent
Either anatomic variant or acquired abnormality
Present in 5% of cholecystograms
Other images: person (bust) with phrygian cap
Micro: may have small mucosal fold with disorganized muscle layer; may have focal adenomyoma at apex of inverted fundus
Long mesentery or no firm attachment to liver
At risk for torsion
Cholecystitis
Present in 5-10% of cholecystectomy specimens
Either gallstone associated (acute calculous cholecystitis) or not (acute acalculous cholecystitis)
10% perforate without treatment
Treatment: cholecystectomy
Gross: enlarged, distended gallbladder; congested vessels (“angry red color”), serosal and mucosal exudate, thickened wall with edema and hemorrhage; ulcers with blood clot, pus and bile
Gross images: acute (with empyema) and chronic cholecystitis with gallstone #1, #2, red mucosa #1, #2
Micro: initially edema, congestion, hemorrhage, fibrin deposition in and around muscular layer; later mucosal and mural necrosis with neutrophils; variable reactive epithelial changes resembling dysplasia; finally myofibroblastic proliferation with chronic inflammatory infiltrate; also fresh thrombi within small veins
Note: diagnosis of dysplasia should be made cautiously if extensive ulceration or acute inflammation
DD: leptospirosis
Acute calculous cholecystitis
90% of cases
Mean age 60 years, 60% women
Abdominal pain, right upper quadrant tenderness, nausea, vomiting, fever, leukocytosis, mild jaundice
50% of those with jaundice have coexisting choledocholithiasis
Due to stone impaction, versus biliary colic, which is due to intermittent obstruction
50% have bacterial infection (E. coli, Enterobacter, Enterococcus, Klebsiella, Clostridium, Peptostreptococcus, Bacteroides)
1% mortality; perforation unlikely if early operation
Pathophysiology: chronic obstruction causes increased intraluminal pressure, vascular compromise, stasis and concentration of bile within lumen, mucosal damage, release of cellular enzymes, release of inflammatory mediators
Acute acalculous cholecystitis
10% of cases
2/3 male, mean age 50+ years
Often only fever or hyperamylasemia
Patients usually severely debilitated, due to severe trauma, sepsis, shock, burns, cancer, diabetes, multiple blood transfusions, surgery, torsion, cystic duct obstruction from various causes
May be associated with infection by CMV, cryptosporidia or microsporidia in AIDS patients
10-50% mortality
Case reports of leptospirosis in athletes swimming in freshwater lake mimicking acute cholecystitis, Hum Path 2001;32:750
Cocaine related acute cholecystitis
Young, otherwise healthy patients
Vascular thrombi present
Other parts of GI tract also affected
Most cholecystectomies are performed for intermittent obstruction of gallbladder neck / cystic duct by gallstones, causing biliary colic
95% are associated with cholelithiasis
75% women, ages 40+
Complications: acute cholecystitis, choledocholithiasis, acute pancreatitis, gallstone ileus, biliary fistulas
Bacteria present in 11-30%, similar organisms as in acute cholecystitis
Giardia lamblia: associated with IgA deficiency, achlorhydria, malabsorption
Salmonella typhi: associated with chronic carrier states
Chronic active cholecystitis: with intraepithelial neutrophils
Rokitansky-Aschoff sinuses: tubular structures present within the wall in 90%, likely herniations or diverticula due to increased intraluminal pressure; called Luschka’s ducts if subserosal
Gross: variable thickening of gallbladder wall, variable adhesions
Micro: mild chronic inflammation with Rokitansky-Aschoff sinuses, granulomas (from ruptured Rokitansky-Aschoff sinuses), smooth muscle hypertrophy; neuromatous hyperplasia, hyalinized collagen, dystrophic calcification, lymphoid aggregates (5%); variable mucosal changes (normal, atrophic, ulcerated); variable metaplastic change
Micro images: thickened wall with Rokitansky-Aschoff sinuses; atrophic mucosa and fibrotic lamina propria
Virtual slides: chronic cholecystitis
DD: normal gallbladder (if minimal inflammation), primary sclerosing cholangitis or extrahepatic bile duct obstruction (if abundant plasma cells and no gallstones),
Diffuse lymphoplasmacytic acalculous cholecystitis
Relatively sensitive for primary sclerosing cholangitis, but does not distinguish between primary and secondary cholangiopathies
Associated with lymphoplasmacytic sclerosing pancreatitis
Micro: diffuse, mucosal based, dense lymphoplasmacytic infiltrate without cholelithiasis
References: AJSP 2003;27:1313, AJSP 2003;27:441
AIDS related cholecystitis
Often acalculous
40% have opportunistic infections (cryptosporidia, CMV, microsporidia), which are usually also present at other sites
Cryptosporidia: small, round, basophilic organisms at luminal epithelial border
CMV: usually erosions and deep ulcers; marked microscopic changes
Microsporidia: Enterocytozoon bieneusi, less often Septata intestinalis; S. intestinalis within epithelium and lamina propria; can identify with H&E stain, but often missed
Usually no opportunistic infections if HIV+ but not classified as AIDS
Rare form of acute cholecystitis
2/3 men, usually 50-70 years old
Associated with diabetes and peripheral atherosclerotic disease
May be due to vascular compromise of cystic artery
Associated with acalculous disease, gallbladder perforation, Clostridium welchii and E. coli infection
Gross images: transmural infarction and hemorrhagic necrosis
Micro images: multiple areas of gas (long arrows) in wall
References: Radiographics 2002;22:543
Restrict usage to inflammatory infiltrates composed almost entirely of eosinophils, since eosinophils are common in subacute cholecystitis
1-5% of resected gallbladders
Often involves muscular layer, but may be transmural or mucosal
Associated with gallstones, fibroblasts
Causes: idiosyncratic reaction to biliary contents; less commonly due to erythromycin, ampicillin, cephalosporin, interleukin 2 and lymphokine activated killer cells, peripheral eosinophilia, hypereosinophilic syndrome, atopy, eosinophilic enterocolitis or appendicitis, parasitic infection, eosinophilic cholangitis, lymphoplasmacytic sclerosing pancreatitis (AJSP 2003;27:334)
Churg-Strauss syndrome: granulomatous angiitis with eosinophilia
Also called lymphoid polyp
Well formed germinal centers throughout gallbladder wall
May grossly resemble polyps up to several mm in size
Associated with typhoid fever, primary sclerosing cholangitis
Occurs in 15% of acute cholecystitis cases
Mural infarction, with perforation in 25%
Associated with Clostridium perfringes and air in gallbladder (pneumobilia)
Causes: Mycobacterium tuberculosis, fungi, Crohn’s disease, primary biliary cirrhosis, parasites
DD: xanthogranulomatous cholecystitis (below)
Rare
Iron and calcium positive calcospherites (Michaelis-Guttmann bodies) in cytoplasm of histiocytes
0.5% of cholecystectomies
20% of cases associated with gallbladder carcinoma
Gross: pearly white appearance due to dystrophic calcification
Gross images: porcelain gallbladder #1; #2
Xanthogranulomatous cholecystitis
1-2% of surgically excised gallbladders
Usually women ages 60-70 years
Due to rupture of Rokitansky-Aschoff sinuses with extravasation of bile, or ulceration of gallbladder mucosa
Complications include perforation, abscess formation, fistulous tracts, extension to liver, colon or soft tissue
Associated with malignancy
Gross: yellow-brown, poor to well-demarcated foci of wall thickening with variable ulceration, simulates neoplasm
Gross images: diffuse wall thickening #1, #2
Micro: foamy macrophages or macrophages with ceroid, bile or iron; also cholesterol clefts and multinucleated giant cells; may be focal, nodular or diffuse; may contain lymphocytes, plasma cells, foreign body giant cells and neutrophils
Micro images: foamy macrophages and chronic inflammatory cells #1, #2, #3
DD: carcinoma, sarcoma, inflammatory myofibroblastic tumor, other granulomatous cholecystitis
Miscellaneous non-tumor disorders
Also called adenomyomatosis, diverticular disease of gallbladder
Benign; usually asymptomatic; relatively common (9% of cholecystectomy specimens)
Generalized, segmental or localized types
Generalized: diffuse wall thickening (up to 5x normal) with intramural diverticula resembling cystic spaces within the wall
Segmental: focal thickening in gallbladder wall, usually body, giving it an hourglass configuration
Localized: fundus has nodules from 0.5 to 2.5 cm with gray-white cut surface containing multiple cysts; may cause gallbladder inversion; also called adenomyoma
80% associated with chronic cholecystitis; rarely associated with dysplasia and carcinoma
Gross images: diffuse wall thickening with polypoid nodules #1, #2, fundic mass containing multiple cysts, diffuse wall thickening with embedded pigment stones into cystically dilated glands
Micro: circumscribed lesion of Rokitansky-Aschoff sinuses, often containing inspissated bile concretions, lined by columnar to cuboidal epithelium, within hyperplastic smooth muscle; surface epithelium may be papillary; may have reactive epithelial changes and metaplasia; rarely has perineural and intraneural invasion
Micro images: papillary hyperplasia with hyperplastic smooth muscle
DD: chronic cholecystitis
Stones in common bile duct
Primary: originate in common bile duct
Secondary: originate in gallbladder
40% of common bile duct stones are brown stones, usually associated with recurrence pyogenic cholangitis
Diagnosis: ERCP (95% sensitive and specific), ultrasound is only 50% sensitive
Also called gallstones
Accounts for 1% of national heath care budget
Affects 10% of adults in developed countries (80% are silent) vs. <1% of children
80% of gallstones in West are cholesterol stones with 50% or more crystalline cholesterol monohydrate
20% of gallstones in West are pigment stones composed of bilirubin calcium salts
Gallstones impact at neck just proximal to cystic duct; typically within lumen but may be intramural
Risk factors: Pima, Hopi or Navajo (75% of stones are pure cholesterol vs. 25% in industrialized vs. minimal in developing countries), also Scandinavians, Chileans, Mexican-Americans, increasing age (>50% risk by age 80); “fat, fertile [multiple pregnancies], 40, female”, obesity, rapid weight loss, gallbladder stasis, genetic disorders that impair bile salt synthesis/secretion or increase cholesterol levels (serum or biliary), low HDL levels
Biliary sludge typically occurs before gallstones
Estrogens from birth control pills or pregnancy increase expression of hepatic LDL receptors, which increase cholesterol uptake, which stimulate HMG CoA reductase, which synthesizes cholesterol
Pigment stone risk factors are increased unconjugated bilirubin (from hemolytic syndromes, ileal dysfunction/bypass, bacterial contamination of biliary tree)
Clofibrate: anti-cholesterol drug that increases HMG CoA reductase activity and decreases conversion of cholesterol to bile acids by reducing cholesterol 7 alpha hydroxylase activity, causes excess biliary secretion of cholesterol
Symptoms: usually none, but may have biliary colic (severe, right upper quadrant pain)
Diagnosis: ultrasound (95% sensitive and specific for gallstones 2 mm or larger or gallbladder sludge), Xrays detect 10-25% of gallstones that are radiopaque due to calcium
Treatment: laparoscopic cholecystectomy if symptomatic or in children, Native Americans, patients with sickle cell disease or porcelain gallbladder, stones 3 cm or larger
Complications: 1-2% have acute or chronic cholecystitis, choledocholithiasis, cholangitis, empyema, gallstone ileus, acute pancreatitis
Mirizzi’s syndrome: rare; stone impacting in cystic duct or gallbladder neck causes extrinsic compression or obstruction of common bile duct, causing jaundice
Report: presence of biliary sludge, number, size and type of gallstones
Gross: 85% are 2 cm or less
Micro: minimal/mild lymphocytic mucosal inflammation, Rokitansky-Aschoff sinuses, fibrosis, thickening of muscularis propria, cholesterolosis, focal epithelial metaplasia (pyloric/gastric mucin cell metaplasia or intestinal metaplasia)
References: AJSP 2003;27:1313
Present in 20% of cholecystectomy specimens, usually adult multiparous women
Asymptomatic
Associated with bile supersaturation with cholesterol, but not with increased serum cholesterol
Due to accumulation of cholesterol esters and triglycerides in subepithelial macrophages and gallbladder epithelium
Gross: yellow, flat deposits on mucosal surface, focal or diffuse; may have speckled appearance (“strawberry gallbladder”), 20% are associated with cholesterol polyps
Gross images: image
Micro: foamy macrophages in lamina propria and epithelium; villous mucosal hyperplasia with macrophages at tips of villi; usually no or minimal cholecystitis; may be polypoid, rarely with heterotopic bone (AJSP 2000;24:895); usually changes are restricted to gallbladder and don’t involve extrahepatic bile ducts
Virtual slides: cholesterolosis
Positive stains: Oil red O / Sudan black (on frozen tissue)
Biliary-enteric fistulas found in 0.2 to 5.0% of patients with biliary tract surgery for non-malignant disease
90% due to cholelithiasis, 10% due to penetrating peptic ulcers of stomach or duodenum
Pathophysiology: gallstones cause inflammation and necrosis of gallbladder or bile duct wall, leading to intestinal adhesions, leading to fistula
Sites: from gallbladder in 90%, biliary tract in 10%; usually to duodenum, also colon
Diagnosis: air within biliary tree by Xray, vomiting or passing a large gallstone
Mortality: 15%
Complications: gallstone ileus
Gallbladder in extrahepatic bile duct obstruction
Diffuse, bandlike, superficial chronic inflammatory infiltrate of predominantly plasma cells suggests primary sclerosing cholangitis, ulcerative colitis
Chronic active cholecystitis and chronic acalculous cholecystitis suggests primary sclerosing cholangitis, choledocholithiasis or other extrahepatic bile duct obstruction
Gallstones composed of insoluble bile components: cholesterol, calcium bilirubinate, calcium salts (organic and inorganic), bile salts, mucin glycoproteins
In U.S., 75-85% are cholesterol stones, 15-25% are pigment stones
Calcium stones are gray-white and amorphous; very uncommon
Calcium carbonate may fill lumen as thick, inspissated, cream-gray to yellow-green putty-like material
Cholesterol stones
75-85% of all gallstones
Only 10% are pure (at least 90% cholesterol), the remainder are mixtures with at least 60% cholesterol by weight
Cholesterol monohydrate precipitates when no longer soluble in bile; initially bile supersaturation with cholesterol occurs; then nucleation (initial crystallization), then stone growth facilitated by bile stasis and mucin hypersecretion
Pure and mixed occur predominantly in women; also associated with increasing age, obesity, rapid weight loss, diabetes, ileal disease, multiple pregnancies, total parenteral nutrition, various drugs, specific ethnic groups
Gross: less than 1 cm to 4 cm; single or multiple; white-yellow, round/oval with crystalline cut surface
Gross images: multiple white-yellow stones, crystalline cut surface
Pigment stones
15-25% of all gallstones
Associated with increasing age
Less than 25-35% cholesterol
Brown (not black) stones associated with infected bile (usually E. coli) due to acute cholecystitis or choledocholithiasis with cholangitis
Black stones associated with older age, chronic hemolysis, cirrhosis, sclerosing cholangitis (increased unconjugated bilirubin in bile)
Composed of calcium bilirubinate, calcium salts, mucin glycoprotein
Gross: multiple shiny black stones, 0.2 to 5 cm, rarely brown in US (more commonly brown in Japan)
Gross images: multiply shiny black stones
Bowel obstruction due to gallstone entering intestine through cholecystoenteric fistula
Occurs in 20% of cases of gallstones passing into intestine
Usually single stones, 3-4 cm
Involves distal ileum (65-80%), also jejunum (20%), colon (3%), rarely appendix
Gallbladder usually small, fibrotic with adhesions
DD: enterolith (bile acid stones that form in situ within the bowel)
Distended gallbladder containing clear and watery (hydrops) or mucoid secretions (mucocele), instead of bile
Adult cases almost always due to impacted stones in ampulla or cystic duct; rarely due to regional tumors causing compression
Pediatric cases associated with Kawasaki syndrome or other inflammatory narrowing of cystic duct
Mucoceles that perforate may cause pseudomyxoma peritonei
Gross: thickened gallbladder wall
Micro: adults - fibrous replacement of muscular wall; rarely muciphages simulating signet ring adenocarcinoma; children - thin wall with flattened epithelium and sparse inflammation
Usually gastric or intestinal, rarely squamous
Associated with older age, gallstones
Gastric gland metaplasia
66-84% of cholecystectomy specimens
Pyloric, antral or mucous glands
Glands usually scattered in lamina propria but may extend into muscular layer
May form polyps
Don’t call adenoma unless dysplasia present
Intestinal metaplasia
12-52% of cholecystectomy specimens
Goblet cells, endocrine cells, Paneth cells, absorptive cells; also pyloric gland metaplasia
Rarely forms polyps
Usually secondary to inflammatory disorders (chronic cholecystitis [5-20%] or cholelithiasis, adenomyomatous hyperplasia, primary sclerosing cholangitis, ulcerative colitis), cholesterolosis (up to 100%) or anomalous arrangement of pancreaticobiliary duct (40-90%)
Diffuse or focal
Micro: single layer of columnar epithelium in papillary mucosal folds, may be villiform; basal nuclei, no atypia
Rare
Associated with cholecystitis, but only 20% have gallstones or sludge
Vasculitis often due to polyarteritis nodosa (involves gallbladder at autopsy in 10-40%)
Benign gallbladder tumors
By definition, contains at least low grade dysplastic epithelium
Found in 0.5% of cholecystectomy specimens, usually asymptomatic
Increased prevalence found with familial adenomatous polyposis or Peutz-Jeghers syndrome
70% women
Invasive carcinoma rare if < 1 cm
Entire lesion should be submitted for microscopic examination
Not a premalignant lesion since different molecular abnormalities from carcinoma, Hum Path 1999;30:21
Treatment: total excision
Gross: 3-25 mm polypoid structure projecting into lumen; may be sessile; 90% are single
Gross images: tubular adenoma
Micro: usually tubular with pyloric gland features; papillary or intestinal types associated with high grade dysplasia; may have squamous morules
Micro images: tubular adenoma #1, #2, papillary adenoma
Positive stains: estrogen receptors (50%)