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Gallbladder

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Revised: 20 October 2014
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

Anatomy (normal) - Gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Pear shaped saccular structure for bile storage in gallbladder fossa of posterior right hepatic lobe
● Attached to liver by loose connective tissue; and to duodenum by cholecystoduodenal ligament
● 10 x 4 cm, but depends on volume of bile (normal 40-70 ml)
● Wall thickness 1-2 mm
● Has fundus, body and neck

Terminology
=========================================================================

Distal fundus: extends beyond anterior liver margin
Central body: most of gallbladder
Neck: narrows as it joins the cystic duct
Cystic duct: 3 cm tubular structure, located in right free edge of lesser omentum, has spiral valve of Heister
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

Drawings
=========================================================================



Relationship to liver

Virtual slides
=========================================================================



Gallbladder and liver



Histology (normal) - Gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Has mucosa, muscularis propria and serosa on free surface
● No muscularis mucosa or submucosa is present

Terminology
=========================================================================

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
● Few PAS+ apical vacuoles; 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
● Histologically composed of lobular aggregates of small ductules lined by bland cuboidal to columnar biliary type epithelium (Am J Surg Pathol 2011;35:883)

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

Virtual slides
=========================================================================



Normal gallbladder

Positive stains
=========================================================================

Surface epithelium: EMA, low molecular weight keratin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, polyclonal CEA



Embryology


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Develops with bile duct and liver during week 4 as ventral bud (hepatic diverticulum) from caudal foregut (Dig Surg 2010;27:87)
● 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
=========================================================================



Various images



Normal physiology


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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
● 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

Bile constituents
=========================================================================

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

Micro images
=========================================================================



Enterohepatic circulation



Congenital anomalies - general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Includes, in addition to topics below, agenesis of hepatic or common bile duct, bilobed gallbladder due to longitudinal or transverse septum, hypoplastic narrowing of biliary channels (true biliary atresia)



Congenital anomalies

Abnormal position


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare
● Left sided (with or without situs inversus, Am Surg 2012;78:492), intrahepatic (5%), retroperitoneal, suprahepatic
● Also within falciform ligament, lesser sac or abdominal wall

Case reports
=========================================================================

● 78 year old woman presenting with shortness of breath, desaturation, hypercapnia and hypoxemia (J La State Med Soc 2010;162:150)



Congenital anomalies

Agenesis (absence)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare
● 50% discovered at autopsy
● Usually no cystic duct either
● Associated with choledocholithiasis, duodenal atresia and other congenital anomalies
● No clinical significance
● Nonvisualization of fetal gallbladder on ultrasound increases the risk of cystic fibrosis (Prenat Diagn 2012;32:21)

Case reports
=========================================================================

● 45 year old woman with obstructive jaundice (Turk J Gastroenterol 2011;22:216)
● 51 year old woman with right upper abdominal discomfort (Dtsch Med Wochenschr 2012;137:937)
● Gallbladder agenesis with concurrent, solitary, intrahepatic biliary duct cyst (Am Surg 2011;77:E202)



Congenital anomalies

Cysts


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● May begin as pseudodiverticula (Rokitansky-Aschoff sinuses) with progressive occlusion of communication with gallbladder



Congenital anomalies

Diverticula


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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



Congenital anomalies

Duplication


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Excessive budding of the caudal diverticulum
● Duplicated cystic ducts may enter CBD separately (H-type) or united (Y-type) or rarely drain independently into hepatic ducts
● Stones, inflammatory conditions and tumors preferentially involve one of the gallbladders

Case reports
=========================================================================

● 5 year old girl with jaundice, hepatosplenomegaly and pancytopenia (Tunis Med 2011;89:798)
● 58 year old man with right upper quadrant pain (JSLS 2010;14:611)
● Two separate gallbladders, one main and one accessory, each with its own cystic duct (Ital J Anat Embryol 2011;116:61)
● Triple gallbladder (Am J Gastroenterol 2011;106:1861)

Clinical images
=========================================================================



Intraoperative images

Diagrams
=========================================================================



Types of gallbladder duplication



Congenital anomalies

Heterotopia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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 arises as intramural nodules, plaques or polyps, in neck or cystic duct, rarely with peptic ulceration
● Pancreatic heterotopia has acinar tissue, rarely islets, that may cause acute pancreatitis in gallbladder (Ryoikibetsu Shokogun Shirizu 1996;(9):360)

Case reports
=========================================================================

● 36 year old man (Cir Esp 2013;91:130)
● 62 year old woman and 78 year old man (Gut 2001;48:719)
● 72 year old woman and 83 year old woman (G Chir 2011;32:255)

Micro images
=========================================================================



Gastric heterotopia


Pancreas heterotopia of common bile duct


Various images



Congenital anomalies

Hourglass gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Divided by central constriction
● Variant of transverse septate gallbladder divides lumen into proximal and distal cavity
● Inflammatory changes and stone formation common in distal portion
● Usually acquired, due to septum of inflamed fibrous tissue or adenomyomatous hyperplasia



Congenital anomalies

Hypoplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Occurs when caudal bud is incompletely developed or when solid stage of bud is not recanalized
● Associated with extrahepatic biliary atresia

Micro description
=========================================================================

● Compressed epithelium-lined structures, fibrous tissue, smooth muscle strands, inflammatory cells in gallbladder fossa and porta hepatis

Differential diagnosis
=========================================================================

● Acquired postinflammatory fibrotic contraction



Congenital anomalies

Micro gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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 anomalies

Multiseptate gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Congenital or acquired
● Results from incomplete vacuolization of developing gallbladder bud or persistent “wrinkling” of gall bladder wall
● 3-10 communicating compartments lined by columnar epithelium
● Septa cause impaired motility, stasis of bile flow, and symptoms of right upper quadrant pain, nausea, vomiting
● Stones often present in adults
● May be associated with biliary tract abnormality
● Combination of USG (ultrasound) and MRCP is most useful for diagnosis

Case reports
=========================================================================

● 9 month old girl with acute vomiting (Case Rep Gastrointest Med 2011;2011:470658)
● 5 year old girl with recurrent attacks of abdominal pain for 2 years (Diagn Interv Radiol 2010;16:306)
● 29 year old woman with recurrent right upper quadrant pain (Case Report Med 2011;2011:162853)
● 46 year old Japanese woman with gastric carcinoma (World J Gastroenterol 2005;11:6066)

Micro images
=========================================================================



Various images



Congenital anomalies

Phrygian cap


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Inversion of distal fundus into body, to which it may become adherent (Indian J Gastroenterol 2008;27:194)
● Either an anatomic variant or an acquired abnormality
● Present in 5% of cholecystograms

Case reports
=========================================================================

● 51 year old woman with a pain in right upper abdominal quadrant and emesis (Can J Surg 2003;46:50)

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● May have small mucosal fold with disorganized muscle layer
● May have focal adenomyoma at apex of inverted fundus

Other images
=========================================================================



Bust of person with phrygian cap



Congenital anomalies

Wandering gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Long mesentery or no firm attachment to liver (Br Med J 1975;3:193, J Radiol 2000;81:1591)
● At risk for torsion, herniation

Case reports
=========================================================================

● 60 year old man with acute onset diffuse abdominal pain (Saudi J Gastroenterol 2010;16:50)
● 65 year old woman with hypoplasia of right hepatic lobe (Acta Chir Belg 2003;103:425)
● 70 year old woman (Am J Surg 2008;196:240)



Cholecystitis

Acute cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Present in 5-10% of cholecystectomy specimens
● Either gallstone associated (acute calculous cholecystitis) or not (acute acalculous cholecystitis)
● 10% perforate without treatment
Note: diagnosis of dysplasia should be made cautiously if extensive ulceration or acute inflammation

Treatment
=========================================================================

● Cholecystectomy

Gross description
=========================================================================

● 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
=========================================================================



Red mucosa


Acute (with empyema) and chronic cholecystitis with gallstone

Micro description
=========================================================================

● 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

Micro images
=========================================================================



Reactive changes in acute cholecystitis

Virtual slides
=========================================================================



Red mucosa

Differential diagnosis
=========================================================================

● Leptospirosis (Hum Pathol 2001;32:750)


Acute calculous cholecystitis

General
=========================================================================

● 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 such as lysolecithin and prostagladins
● Gall bladder volume increases as acute cholecystitis progresses to gangrene or empyema
● Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones (World J Gastroenterol 2010;16:4341)
● As the weight, volume and size of the stone increases, gall bladder mucosa changes from cholecystitis, hyperplasia, metaplasia, dysplasia, to carcinoma (Trop Gastroenterol 2012;33:39)
● Eosinophils accumulate in gallbladder mucosa in young patients (Pol J Pathol 2011;62:41)


Acute acalculous cholecystitis

General
=========================================================================

● 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

Pathophysiology
=========================================================================

● Raised prostaglandin E levels (cause damage), tissue anoxia, bacterial contamination, stasis and changes in bile salt concentration

Micro description
=========================================================================

● Bile infiltration is more prominent and extends deep to muscle layer, WBC margination of blood vessels and lymphatic dilation

Additional references
=========================================================================

Histopathology 2005;47:485, Semin Gastrointest Dis 2003;14:178, World J Gastroenterol 2003;9:2821, Dig Dis Sci 2003;48:1960


Cocaine related acute cholecystitis

General
=========================================================================

● Young, otherwise healthy patients
● Vascular thrombi present
● Other parts of GI tract also affected

Additional references
=========================================================================

Med Clin (Barc) 1985;85:82



Cholecystitis

AIDS related cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 40% have opportunistic infections (cryptosporidia, CMV, microsporidia), which are usually also present at other sites
● Usually no opportunistic infections if HIV+ but not classified as AIDS
● Often acalculous

Specific infections
=========================================================================

CMV:
● Usually erosions and deep ulcers
● Marked microscopic changes

Cryptosporidia:
● Small, round, basophilic organisms at luminal epithelial border

Microsporidia:
Enterocytozoon bieneusi, less often Septata intestinalis
S. intestinalis within epithelium and lamina propria
● Can identify with H&E stain, but often missed

Case reports
=========================================================================

● 31 year old woman with acalculous cholecystitis and sclerosing cholangiopathy (Br J Radiol 2009;82:699)
● 35 year old man with acalculous cholecystitis due to Cyclospora cayetanensis (Clin Infect Dis 2001;33:E140)
● 37 year old woman of Tanzanian origin presented with symptoms of cholecystitis, sepsis and oral candidiasis (BMJ Case Rep. 2011 Mar 1;2011. pii: bcr0820103292. doi: 10.1136/bcr.08.2010.3292.)
● Cholecystitis as the initial manifestation of disseminated cryptococcosis (AIDS 2007;21:2111)

Micro images
=========================================================================



Cryptosoridium parvum


Cyclospora



Cholecystitis

Chronic cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)

General
=========================================================================

● 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+
● Bacteria present in 11-30%, similar organisms as in acute cholecystitis
Complications: acute cholecystitis, acute pancreatitis, biliary fistulas, choledocholithiasis, gallstone ileus
IBD Related changes: Two inflammatory patterns that occur more often in ulcerative colitis patients are marked chronic cholecystitis and acute serositis, while nodular lymphoid aggregates are more common in Crohn's disease patients (J Crohns Colitis 2012;6:895)
Giardia lamblia: associated with IgA deficiency, achlorhydria, malabsorption
H. pylori: may be present, but association with disease is unclear (J Infect Dev Ctries 2009;3:856)
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 description
=========================================================================

● Variable thickening of gallbladder wall, variable adhesions

Micro description
=========================================================================

● 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


Metaplastic changes gastric


Intestinal

Virtual slides
=========================================================================



Chronic cholecystitis

Differential diagnosis
=========================================================================

Normal gallbladder: if minimal inflammation
Primary sclerosing cholangitis or extrahepatic bile duct obstruction: if abundant plasma cells and no gallstones


Diffuse lymphoplasmacytic acalculous cholecystitis

General
=========================================================================

● Associated with lymphoplasmacytic sclerosing pancreatitis (Am J Surg Pathol 2003;27:441)
● Relatively sensitive for primary sclerosing cholangitis, but does not distinguish between primary and secondary cholangiopathies (Am J Surg Pathol 2003;27:1313)

Micro description
=========================================================================

● Diffuse, mucosal based, dense lymphoplasmacytic infiltrate without cholelithiasis

Micro images
=========================================================================



Various images



Cholecystitis

Emphysematous cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare form of acute cholecystitis with gas in gallbladder wall, associated with diabetes and peripheral atherosclerotic disease
● 2/3 men, usually 50-70 years old, diagnosed with ultrasonographic studies
● 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


Perforation within a large area of transmural necrosis

Micro images
=========================================================================



Multiple areas of gas (long arrows) in wall

Additional references
=========================================================================

Radiographics 2002;22:543, ANZ J Surg 2011;81:106, CMAJ 2012;184:E81, Am J Surg 2010;200:e53



Cholecystitis

Eosinophilic cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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
● Churg-Strauss syndrome: granulomatous angiitis with eosinophilia

Etiology
=========================================================================

● Idiosyncratic reaction to biliary contents
● Less commonly due to ampicillin, atopy, cephalosporin, eosinophilic cholangitis, eosinophilic enterocolitis or appendicitis, erythromycin, hypereosinophilic syndrome, interleukin 2 and lymphokine activated killer cells, lymphoplasmacytic sclerosing pancreatitis, parasitic infection, peripheral eosinophilia (Am J Surg Pathol 2003;27:334)

Case reports
=========================================================================

● 29 year old obese man (Ann Clin Lab Sci 2007;37:182)
● 40 year old woman with Ascariasis-induced eosinophilic cholecystitis (HPB (Oxford) 2006;8:72)
● 40 year old woman (Cir Esp 2012 May 5 [Epub ahead of print])

Clinical images
=========================================================================



Various images

Gross images
=========================================================================



Various images

Micro images
=========================================================================



Various images



Cholecystitis

Follicular cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Well formed germinal centers throughout gallbladder wall
● Also called lymphoid polyp
● May grossly resemble polyps up to several mm
● Associated with typhoid fever, primary sclerosing cholangitis, gram negative bacterial infection of bile (Acta Pathol Jpn 1979;29:67)



Cholecystitis

Gangrenous cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Occurs in 15% of acute cholecystitis cases
● Mural infarction, with perforation in 25%
● Associated with Clostridium perfringes and air in gallbladder (pneumobilia)
● High mortality rate

Case reports
=========================================================================

● 79 year old man with acute cholecystitis (J Med Case Rep 2011;5:199)

Gross images
=========================================================================



Various images



Cholecystitis

Granulomatous cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Etiology
=========================================================================

● Crohn’s disease, fungi, Mycobacterium tuberculosis (Indian J Pathol Microbiol 2008;51:175), parasites, primary biliary cirrhosis

Case reports
=========================================================================

● 26 year old woman with abdominal and epigastric pain (Ann Saudi Med 2010;30:244)
● 33 year old woman with panperitonitis due to intestinal perforation and cholecystitis (World J Gastroenterol 2006;12:977)

Micro images
=========================================================================



Tuberculosis

Differential diagnosis
=========================================================================

Xanthogranulomatous cholecystitis



Cholecystitis

Hemorrhagic cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 24 year old woman diagnosed with SLE (Rev Esp Enferm Dig 2011;103:431)

Additional references
=========================================================================

Am J Gastroenterol 1989;84:445



Cholecystitis

Malakoplakia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare in gallbladder; iron and calcium positive calcospherites (Michaelis-Guttmann bodies) in cytoplasm of histiocytes (Histopathology 2005;46:474)

Case reports
=========================================================================

● Gallbladder malakoplakia in type 2 diabetes mellitus (BMJ Case Rep. 2012 Aug 27;2012)
● Malakoplakia of biliary tract and duodenum (Gastroenterol Clin Biol 2003;27:655)



Cholecystitis

Porcelain gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Dense, paucicellular hyaline fibrosis transforming gallbladder wall into relatively thin and uniform band
● Diffusely effaces most of normal structure, some cases show calcifications
● Also called hyalinizing cholecystitis
● 0.5% of cholecystectomies - 20% of cases associated with gallbladder carcinoma

Gross description
=========================================================================

● Pearly white appearance due to dystrophic calcification

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Widely scattered and bland-appearing glands embedded in thin band of hyaline stroma, commonly showing a disappearing lining, leaving behind granular, necrotic intraluminal debris (regression) with or without calcification (Am J Surg Pathol 2011;35:1104)
● Surface epithelium, if preserved, typically shows carcinoma in situ of either denuding or micropapillary types
● Glandular elements in wall should raise suspicion of carcinoma, since benign glands are usually sparse

Differential diagnosis
=========================================================================

Carcinoma of gallbladder: glands have longitudinal axis parallel to the surface, irregular contours, clear cytoplasm with distinct borders, nuclear irregularities, washed-out chromatin



Cholecystitis

Xanthogranulomatous cholecystitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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
● Resembles carcinoma at surgery; often associated with extended surgical resections (Dig Surg 2012;29:187, Gut Liver 2010;4:518)
● Frozen sections may prevent extended resections (Cell Biochem Biophys 2012;64:131)
● Complications include perforation, abscess formation, fistulous tracts, extension to liver, colon or soft tissue
● Associated with malignancy

Case reports
=========================================================================

● 76 year old man with false positive PET scan (World J Gastroenterol 2009;15:3691)
● 80 year old woman with perforation presenting as biloma (Korean J Gastroenterol 2011;58:153)
● Two cases (Acta Gastroenterol Latinoam 2011;41:331)

Gross description
=========================================================================

● Yellow-brown, poor to well-demarcated foci of wall thickening with variable ulceration, simulates neoplasm

Gross images
=========================================================================



Diffuse wall thickening

Micro description
=========================================================================

● 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

Differential diagnosis
=========================================================================

Carcinoma of gallbladder
Granulomatous cholecystitis
● Inflammatory myofibroblastic tumor
● Sarcoma



Miscellaneous non-tumor

Adenomyomatous hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called adenomyomatosis, diverticular disease of gallbladder
● Benign
● Usually asymptomatic
● Relatively common (9% of cholecystectomy specimens)
● 80% associated with chronic cholecystitis
● Rarely associated with dysplasia and carcinoma

Terminology
=========================================================================

● 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

Case reports
=========================================================================

● 34 year old woman with polypoid leiomyosarcoma (Ann Diagn Pathol 2004;8:358)
● Three cases with fundal variant (J Clin Med Res 2010;2:150)

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Two types: (a) numerous Rokitansky-Aschoff sinuses accompanied by smooth muscle hyperplasia and expanded subserosal layer containing numerous nerve trunks; (b) extensively fibrotic gallbladder wall with numerous Rokitansky-Aschoff sinuses but few/no smooth muscle bundles and an expanded subserosal layer containing abundant nerve-trunks; surface epithelium may be papillary
● May have reactive epithelial changes and metaplasia
● Rarely has perineural and intraneural invasion only in the subserosal layer (benign gland-like structures may migrate into nerves due to chemotactic factors or signaling substances with activation of cell receptors, Am J Surg Pathol 2007;31:1598)

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

● Adenocarcinoma or "adenoma malignum"
Chronic cholecystitis



Miscellaneous non-tumor

Choledocholithiasis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Stones in common bile duct
● 40% of common bile duct stones are brown stones, usually associated with recurrent pyogenic cholangitis and older age (J Int Med Res 2009;37:1220)
● Primary: originate in common bile duct
● Secondary: originate in gallbladder

Diagnosis
=========================================================================

● ERCP (95% sensitive and specific), ultrasound is only 50% sensitive

Case reports
=========================================================================

● 27 year old man with sickle cell disease (Intern Med 2008;47:2169)



Miscellaneous non-tumor

Cholelithiasis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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], forty, female”, obesity (Korean J Gastroenterol 2012;59:27), rapid weight loss, gallbladder stasis, genetic disorders that impair bile salt synthesis/secretion or increase cholesterol levels (serum or biliary), low HDL levels
● May be influenced by Apolipoprotein E genotype (Ann Epidemiol 2006;16:763)
● 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)

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

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

Gross description
=========================================================================

● 85% are 2 cm or less

Micro description
=========================================================================

● Minimal/mild lymphocytic mucosal inflammation, Rokitansky-Aschoff sinuses, fibrosis, thickening of muscularis propria (Am J Surg Pathol 2003;27:1313), cholesterolosis, focal epithelial metaplasia (pyloric/gastric mucin cell metaplasia or intestinal metaplasia)



Miscellaneous non-tumor

Cholesterolosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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 description
=========================================================================

● Yellow, flat deposits on mucosal surface, focal or diffuse
● May have speckled appearance ("strawberry gallbladder"), 20% are associated with cholesterol polyps

Micro description
=========================================================================

● 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 (Am J Surg Pathol 2000;24:895)
● Usually changes are restricted to gallbladder and don’t involve extrahepatic bile ducts

Micro images
=========================================================================



Lipid laden histiocytes in lamina propria

Virtual slides
=========================================================================



Cholesterolosis

Positive stains
=========================================================================

● Oil red O / Sudan black (on frozen tissue)

Additional references
=========================================================================

Klin Med (Mosk) 2002;80:14, Minerva Gastroenterol Dietol 2003;49:217, Saudi Med J 2004;25:1226



Miscellaneous non-tumor

Fistula


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Biliary-enteric fistulas found in 0.2 to 5.0% of patients with biliary tract surgery for non-malignant disease (Surgeon 2010;8:67)
● 90% due to cholelithiasis, 10% due to penetrating peptic ulcers of stomach or duodenum
● Complications: gallstone ileus
● Mortality: 15%

Sites
=========================================================================

● From gallbladder in 90%, biliary tract in 10%
● Usually to duodenum, also colon

Pathophysiology
=========================================================================

● Gallstones cause inflammation and necrosis of gallbladder or bile duct wall, leading to intestinal adhesions, leading to fistula

Clinical features
=========================================================================

● Abdominal pain, diarrhea, dyspeptic symptoms, nausea, and weight loss
● Most can be managed laparascopically

Diagnosis
=========================================================================

● Air within biliary tree by Xray, vomiting or passing a large gallstone

Case reports
=========================================================================

● 59 year old woman with cholecystocolic fistula (Saudi J Gastroenterol 2009;15:42)

Clinical images
=========================================================================



Right transverse colon with gall stone in fistula



Miscellaneous non-tumor

Gallbladder in extrahepatic bile duct obstruction


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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



Miscellaneous non-tumor

Gallstone classification


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Gallstones are 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
● Larger stones are associated with carcinoma (Trop Gastroenterol 2012;33:39); also cholesterol, not pigment stones (Aust N Z J Surg 2000;70:667)
● 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

General
=========================================================================

● 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
● Adenomatous hyperplasia and Rokitansky-Aschoff sinuses:associated with mixed and cholesterol stones; not associated with pigment stones (Trop Gastroenterol 2002;23:25)

Gross description
=========================================================================

● Less than 1 cm to 4 cm
● Single or multiple
● White-yellow, round/oval with crystalline cut surface


Pigment stones

General
=========================================================================

● 15-25% of all gallstones
● Associated with increasing age
● Less than 25-35% cholesterol
● Composed of calcium bilirubinate, calcium salts, mucin glycoprotein
● 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)

Gross description
=========================================================================

● Multiple shiny black stones, 0.2 to 5 cm, rarely brown in US (more commonly brown in Japan)

Gross images
=========================================================================



Two pigment gallstones



Miscellaneous non-tumor

Gallstone ileus


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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

Case reports
=========================================================================

● 92 year old man with symptoms and signs of large-bowel obstruction (HPB Surg 2010;2010:153740)

Differential diagnosis
=========================================================================

● Enterolith: bile acid stones that form in situ within the bowel

Additional references
=========================================================================

J Med Life 2010;3:365, CMAJ 2008;179:859



Miscellaneous non-tumor

Hydrops / mucocele


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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

Case reports
=========================================================================

● 24 year old man with right upper quadrant pain with a palpable mass (Prilozi 2011;32:207)
● 31 year old woman with 10 year history of mild, episodic abdominal pain (N Engl J Med 2011;364:e43)
● Massive hydrops mimicking a choledochal cyst (J Pediatr Surg 2011;46:1015)

Gross description
=========================================================================

● Thickened gallbladder wall

Micro description
=========================================================================

Adults:
● Fibrous replacement of muscular wall
● Rarely muciphages simulating signet ring adenocarcinoma

Children:
● Thin wall with flattened epithelium and sparse inflammation



Miscellaneous non-tumor

Metaplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually gastric or intestinal, rarely squamous
● Associated with older age, gallstones


Bone metaplasia

Case reports
=========================================================================

● 29 year old woman with osseous metaplasia (Case of the Week #234)
● 53 year old woman with abdominal pain (South Med J 2009;102:322)
● Bone metaplasia in the gallbladder wall (Eksp Klin Gastroenterol 2011;(8):86)


Cartilaginous metaplasia

Case reports
=========================================================================

● Infant with extrahepatic biliary atresia with cartilaginous metaplasia (J Clin Pathol 2008;61:965)


Gastric gland metaplasia

General
=========================================================================

● 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

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Acid mucin positive (Acta Gastroenterol Latinoam 2007;37:11)


Intestinal metaplasia

General
=========================================================================

● Very common finding in cholecystectomy specimens (up to 86%, Sao Paulo Med J 2008;126:220)
● Goblet cells, endocrine cells, Paneth cells, absorptive cells
● Also pyloric gland metaplasia
● Rarely forms polyps
● Case reports: 78 year old man and 62 year old woman (Gut 2001;48:719)

Micro images
=========================================================================



Various images

Additional references
=========================================================================

Hum Pathol 2009;40:1762, Hum Pathol 2007;38:66, Am J Surg Pathol 2004;28:1253, J Clin Pathol 2006;59:328)


Squamous metaplasia

Case reports
=========================================================================

● 47 year old woman with gastric heterotopia and squamous metaplasia (Acta Gastroenterol Latinoam 2007;37:164)
● 56 year old woman with pseudoepidermoid cyst arising from exuberant squamous metaplasia (Arch Pathol Lab Med 2005;129:e138)

Micro images
=========================================================================



Various images



Miscellaneous non-tumor

Papillary hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 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

Case reports
=========================================================================

● 12 year old girl with biliary colic (J Pediatr Surg 2001;36:1584)
● Primary diffuse papillary hyperplasia of gallbladder (Pathology 2006;38:591)

Micro description
=========================================================================

● Single layer of columnar epithelium in papillary mucosal folds, may be villiform
● Basal nuclei, no atypia



Benign gallbladder tumors

Signet ring cells


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Represent hyperplastic and degenerative change of mucosal goblet cells, non-neoplastic (Hum Pathol 2009;40:326)
● Seen on mucosal surface and lumen of tubules

Micro description
=========================================================================

● Signet ring cells that lack nuclear atypia, arranged in superficial and intraluminal nests
● Admixture with histiocytes and other inflammatory cells

Micro images
=========================================================================



Signet-ring cells in gallbladder wall immediately beneath mucosa


Signet-ring cells arranged in nodular collections within glandular lumina surrounded by lamina propria; are AE1-AE3+

Positive stains
=========================================================================

● Mayer's mucicarmine; AE1/AE3

Differential diagnosis
=========================================================================

● Signet ring cell carcinoma



Miscellaneous non-tumor

Vasculitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare
● Associated with cholecystitis, but only 20% have gallstones or sludge
● Vasculitis often due to polyarteritis nodosa (involves gallbladder at autopsy in 10-40%)

Case reports
=========================================================================

● Polyarteritis nodosa of gallbladder (Cases J 2009;2:9300)
● p-ANCA associated vasculitis associated with cholecystitis (J Clin Rheumatol 2009;15:75)

Micro images
=========================================================================



Fibrinoid necrosis of small artery associated with lymphocytes and macrophages



Benign gallbladder tumors

Adenoma of gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Classified as pyloric, intestinal, foveolar and biliary
● Intestinal subtypes includes tubular, papillary and tubulopapillary (Hum Pathol 2012;43:1506)
● 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
● Carcinoma within adenoma found in 23% in one study (Korean J Gastroenterol 2010;55:119), but 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 Pathol 1999;30:21)
● Mutations in RAS/RAF/MAPK pathways in adenomas, not adenocarcinomas (Appl Immunohistochem Mol Morphol 2011;19:133)
● Pyloric gland adenoma can progress to carcinoma and be associated with invasion and fatal outcome (Am J Surg Pathol 2012;36:1279)

Treatment
=========================================================================

● Total excision

Gross description
=========================================================================

● 3-25 mm polypoid structure projecting into lumen
● May be sessile
● 90% are single

Gross images
=========================================================================



Tubular adenoma

Micro description
=========================================================================

● Biliary adenoma: composed of columnar cells similar to normal biliary cells of gallbladder
● Foveolar adenoma: has low-grade dysplasia
● Pyloric gland adenoma: usually tubular with pyloric gland features; squamoid morules in 28%
● High grade dysplasia common in pyloric and intestinal adenomas

Micro images
=========================================================================



Tubular adenoma

Positive stains
=========================================================================

● MUC5AC and MUC6 in pyloric gland adenoma, CDX2 in intestinal adenoma (Hum Pathol 2012;43:1506)
● Estrogen receptors (50%)
● Pyloric gland adenoma: aberrant CDX2 expression closely associated with nuclear beta-catenin expression and squamous morules (Virchows Arch 2008;453:521)



Benign gallbladder tumors

Adenomyosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● 15-25% of benign polyps
● See also adenomyomatous hyperplasia

Case reports
=========================================================================

● 57 year old woman with Gardner's syndrome presenting with cholangitis (Gastroenterol Clin Biol 2007;31:425)
● 60 year old woman with clinically gangrenous gallbladder (Case of the Week #186)

Gross description
=========================================================================

● 5-25 mm, usually in fundus in muscular layer
● Gray-white

Micro description
=========================================================================

● Hyperplasia of muscularis propria with intramural hyperplastic or cystically dilated glands

Micro images
=========================================================================





Case of Week #186



Benign gallbladder tumors

Cholesterol polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Most common benign polyp (50-90%)
● Morphologic variation of cholesterolosis
● Usually women (75%), 40-50 years old
● Also associated with young patients with high body mass index (J Korean Surg Soc 2012;82:232)

Case reports
=========================================================================

● Adenocarcinoma of the gallbladder confined to a cholesterol polyp (Am J Gastroenterol 1999;94:2568)

Gross description
=========================================================================

● 4-15 mm, yellow, soft, pedunculated, often multiple

Radiology images
=========================================================================



Multiple small pedunculated polyps

Micro description
=========================================================================

● Mucosal projections with lipid-laden macrophages covered by normal gallbladder epithelium

Micro images
=========================================================================



Subepithelial lipid laded macrophages



Benign gallbladder tumors

Granular cell tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Often associated with similar lesions in extrahepatic bile ducts

Case reports
=========================================================================

● 58 year old Japanese man (Acta Pathol Jpn 1985;35:687)

Gross description
=========================================================================

● Nodules in gallbladder wall

Micro description
=========================================================================

● Large cells with abundant, eosinophilic, granular cytoplasm

Positive stains
=========================================================================

● S100, PAS+ granules, inhibin-alpha (Am J Surg Pathol 2001;25:1200)



Benign gallbladder tumors

Hyperplastic / metaplastic polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Common - 25% of benign polyps

Case reports
=========================================================================

● 9 year old girl with pancreaticobiliary maljunction (Pediatr Surg Int 2009;25:999)

Gross description
=========================================================================

● < 5 mm, brown-gray, granular or villiform, sessile or pedunculated, usually multiple

Micro description
=========================================================================

● Usually nodules of pyloric-type glands

Differential diagnosis
=========================================================================

Gastric heterotopia: also parietal and chief cells



Benign gallbladder tumors

Inflammatory polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 15% of benign polyps
● Associated with chronic cholecystitis

Case reports
=========================================================================

● 69 year old man with inflammatory polyp mimicking early polypoid carcinoma.(Case Rep Gastroenterol 2009;3:255)

Gross description
=========================================================================

● 3-15 mm, red-gray-brown, usually sessile and single

Gross images
=========================================================================



Smooth-surfaced polyp

Micro description
=========================================================================

● Sessile mucosal projections with a surface of columnar epithelial cells covering a fibrous stroma with chronic inflammatory cells and lipid-laden macrophages in granulation-type tissue

Micro images
=========================================================================



Nonneoplastic polyp with edematous stroma and infiltration of lymphocytes and plasma cells



Benign gallbladder tumors

Villous papilloma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Associated with metachromatic leukodystrophy in children and adults
● May cause massive hemobilia

Case reports
=========================================================================

● 2 year old girl with metachromatic leukodystrophy (Hum Pathol 1984;15:1192)
● Middle aged woman with acromegaly (World J Gastroenterol 2007;13:3144)
● 76 year old woman with upper abdominal pain (Hepatogastroenterology 1997;44:681)

Micro images
=========================================================================



Foveolar-type tubulopapillary (villous) adenoma arising in Rokitansky-Aschoff sinus; lining cells are tall columnar with abundant cytoplasm and basal nuclei


Diffuse nuclear expression of CDX2 in an intestinal-type papillary (villous) adenoma



Dysplasia

Dysplasia-general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Neoplastic intraepithelial proliferation
● Present in 1-34% of cholecystectomy specimens (severe dysplasia in 1-3%)
● May be associated with invasive carcinoma
● Diagnose with caution if extensive ulceration or acute inflammation
● Extensive sampling recommended after diagnosis (can use jelly roll technique used for placentas)
● Submitting the entire gallbladder in cases of dysplasia is not justified; proper review of the gross specimen and submission of up to 4 additional sections identify all significant lesions (Am J Clin Pathol 2012;138:374)
● Statistical significant association has been noted between intestinal metaplasia and dysplasia (Gastroenterol Hepatol (N Y) 2008;4:735)


Table: dysplasia and intestinal metaplasia

Gross description
=========================================================================

● Granular mucosal patches or no gross findings

Micro description
=========================================================================

● Involves flat mucosa, papillae, Rokitansky-Aschoff sinuses, metaplastic pyloric glands
● Abrupt transition from normal mucosa
● May resemble carcinoma but no desmoplasia
● Often goblet cells
Low grade: crowding and hyperchromatic and elongated nuclei
High grade: low grade features plus stratification; includes carcinoma in situ

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

● Reactive epithelial changes: no abrupt transition from normal mucosa, prominent nucleoli, epithelial atypia proportional to stromal atypia



Dysplasia

Dysplasia-carcinoma sequence


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Suggested route for development of invasive carcinoma of gallbladder (Arch Pathol Lab Med 2005;129:386)

Gallstones → chronic inflammation → antral-type metaplasia → intestinal metaplasia → dysplasia → carcinoma

● Major pathway to invasive gallbladder carcinoma is via dysplasia; adenomas do not appear to be important precursors
● Hyperplasia may not be part of this sequence



Malignant gallbladder tumors

Gallbladder carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Relatively uncommon
● Age 60+ years (mean 72 years), 75% women, usually not resectable
● Metastases to peritoneum and liver, pericholedochal lymph nodes of lesser omentum, occasionally to lungs and pleura
● 90% are adenocarcinoma, 5% squamous cell or adenosquamous, 5% undifferentiated

Epidemiology
=========================================================================

● 2.5 per 100,000 population
● Lower incidence in Asia, where pyogenic and parasitic disease of biliary tree are more common
● More common in American Indians and Hispanics; very rare in blacks
● 6,500 annual deaths in US, but largest cause of cancer death for women in Chile

Clinical features
=========================================================================

● Associated with gallstones (2/3); also adenomyomatosis, anomalous connection between common bile duct and pancreatic duct, cholecystoenteric fistula, Peutz-Jeghers syndrome, polyposis coli / Gardner’s syndrome, porcelain gallbladder, ulcerative colitis
● Often invades liver, common bile duct, stomach, duodenum and transverse colon
● 70% involve liver at diagnosis, 50% involve regional lymph nodes

5 year survival:
● Overall 1% (J Surg Oncol 2008;98:485)
● 85-100% for T1, 30-40% for T2
● Median survival 6 months

Diagnosis
=========================================================================

● Adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages; therefore, preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered (Virchows Arch 2011;459:573)
● Intraoperative bile cytology useful to detect in situ and early invasive carcinoma (Cancer 2005;105:277)

Prognostic factors
=========================================================================

Favorable: papillary histology, low stage
Unfavorable: small cell or undifferentiated types, angiolymphatic invasion, poorly differentiated, high stage, tumor budding and dedifferentiation (Virchows Arch 2011;459:449, Asian Pac J Cancer Prev 2012;13:2511)

Molecular markers, poor prognosis:
● Overexpression of MCM2 or loss of expression of Tat-interacting protein 30 (Hum Pathol 2011;42:1676), overexpression of PEG10 and TSG101 (Pathol Oncol Res 2011;17:859), reduced expression of Raf-1 kinase inhibitory protein (Hum Pathol 2010;41:1609)
● L1 adhesion molecule (Hum Pathol 2011;42:1476)
● Strong cytoplasmic expression of COX2 at invasive fronts (J Clin Pathol 2010;63:1048)

Case reports
=========================================================================

● 22 year old African American man with lack of choleliths (Int J Surg Pathol 2010;18:358)
● 77 year old woman presenting as meningeal carcinomatosis (Arch Pathol Lab Med 2001;125:1120)

Treatment
=========================================================================

● Cholecystectomy (T1 tumors), uncertain for more advanced tumors
● Tumor may recur at trochar site after laparoscopic cholecystectomy

Gross description
=========================================================================

● Fibrosis and thickening of wall, may be papillary and diffuse
● Often associated with gallstones > 3 cm
● Tumor may not be obvious, although liver spread is usually evident at time of diagnosis

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Infiltrative (diffuse thickening and induration of wall with possible fistula formation due to deep ulceration) or exophytic (irregular, cauliflower mass that grows into lumen and invades wall)
● Well formed glands in papillary architecture with wide lumina, atypical cuboidal cells, high grade
● May extend to Rokitansky-Aschoff sinuses (but this does not signify deep invasion)
● Superficial portion is often better differentiated than deeper portion
● May have foci of intestinal differentiation

Micro images
=========================================================================





Various images

Positive stains
=========================================================================

● Keratin, CEA, P504S
New Biomarker: S100A8 (Dig Dis Sci 2012 Jul 18 [Epub ahead of print])

Molecular / cytogenetics description
=========================================================================

● Methylation in the promotor gene is a crucial early event in gall bladder carcinogenesis
● K-ras mutations (Mod Pathol 2003;16:299, Histopathology 2009;55:218), microsatellite instability (small subset) are noted in dysplastic lesions and gall bladder carcinomas (Rev Med Chil 2010;138:595)
● p16 protein overexpression is an early and relatively common event in carcinogenesis of gallbladder (Hepatogastroenterology 2010;57:18, Ann Diagn Pathol 2008;12:161)
● Loss of heterozygosity has been in several chromosomes in dysplasia and carcinomas (Mod Pathol 1999;12:763)
● Significantly higher hTERT indices are seen in low and high grade dysplastic epithelia and in gallbladder adenocarcinomas (J Clin Pathol 2005;58:820)

Differential diagnosis
=========================================================================

● Reactive atypia (see table below)


Table

Additional references
=========================================================================

Am J Surg Pathol 2002;26:758, Radiographics 2001;21:295, Arch Pathol Lab Med 2010;134:1621



Malignant gallbladder tumors

Carcinoma in situ


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Often an incidental finding after cholecystectomy for cholecystitis or cholelithiasis (Arch Pathol Lab Med 2010;134:1621)
● Not associated with tumor related death

Micro description
=========================================================================

● May extend into Rokitansky-Aschoff sinuses resembling invasive carcinoma, but is connected to surface epithelium (Am J Surg Pathol 2004;28:621)
● Mixture of benign and neoplastic epithelium
● Has inspissated bile in long dilated spaces
● Desmoplasia, but no invasion into smooth muscle bundles, no perineurial invasion
● May arise in adenomyomatous hyperplasia


Comparison of CIS with invasive carcinoma

Micro images
=========================================================================



Various images



Malignant gallbladder tumors

Carcinoid tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Carcinoid tumors in general are rare in gallbladder and may be associated with MEN syndromes and Zollinger-Ellison syndrome
● 10 year survival of 36% in one study (Ann Diagn Pathol 2009;13:378)

Case reports
=========================================================================

● 35 year old woman with clinical cholelithiasis (J Indian Med Assoc 2011;109:198)
● 35 year old woman with 20 cm mass (Hepatobiliary Pancreat Dis Int 2009;8:326)
● 38 year old man with von Hippel-Lindau disease and clear cell carcinoid tumor (Am J Surg Pathol 2001;25:1334)
● 46 year old woman with 5 cm mass (World J Surg Oncol 2010;8:12)
● 52 year old woman with 7 mm tumor (BMJ Case Rep. 2009;2009 Epub 2009 May 25)
● 57 year old Caucasian man who underwent laparoscopic cholecystectomy (J Med Case Rep 2011;5:334)
● 64 year old man without von Hippel-Lindau disease (Arch Pathol Lab Med 2003;127:745)

Gross images
=========================================================================



Tumor (arrow) in body and fundus

Micro description
=========================================================================

● Nests and tubules of clear cells containing lipid
● May have pagetoid spread into biliary epithelium
● Resembles clear cell endocrine pancreatic neoplasm associated with von Hippel-Lindau disease

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● AE1-AE3, CK7, chromogranin, synaptophysin
● Inhibin in von Hippel Lindau patients

Negative stains
=========================================================================

● Serotonin

Differential diagnosis
=========================================================================

● Metastatic renal cell carcinoma



Malignant gallbladder tumors

Ewings / PNET


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● Initial case report in 53 year old woman (Arch Pathol Lab Med 2004;128:571)

Micro description
=========================================================================

● Monotonous small round cells with Homer-Wright rosettes

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD99/MIC2, NSE, synaptophysin

Negative stains
=========================================================================

● CD45/LCA, desmin, S100



Malignant gallbladder tumors

Gastrointestinal stromal tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare (<10 cases reported)
● Benign or malignant behavior

Case reports
=========================================================================

● 34 year old woman with right upper quadrant abdominal pain (Arch Pathol Lab Med 2002;126:481)
● 69 year old woman (Am J Surg Pathol 2000;24:1420)
● 72 year old woman with CD117- tumor (HPB Surg 2011;2011:327192)
● Primary malignant gastrointestinal stromal tumor (J Gastrointest Cancer 2011 Nov 16 [Epub ahead of print])

Micro description
=========================================================================

● Bland spindle cells with hyperchromatic nuclei

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD117, vimentin, variable CD34

Negative stains
=========================================================================

● Smooth muscle actin, desmin, myoglobin, cytokeratin, S100



Malignant gallbladder tumors

Large cell neuroendocrine carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare (<10 cases reported)
● Similar to pulmonary counterpart

Case reports
=========================================================================

● Report of two cases (Am J Surg Pathol 2000;24:1424)

Micro description
=========================================================================

● Organoid growth pattern with rosettes and necrosis
● Large cells, prominent nucleoli, coarse chromatin, high mitotic rate
● May have intestinal metaplasia of tumor cells or adjacent mucosa

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Endocrine markers

Negative stains
=========================================================================

● High molecular weight cytokeratin



Malignant gallbladder tumors

Malignant fibrous histiocytoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 63 year old man with massive tumor adherent to stomach, right colon and gallbladder (Case of the Week #144)

Micro images
=========================================================================





Various images - Case of the week #144



Malignant gallbladder tumors

Metastases to gallbladder


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● 6% of patients dying of carcinoma at any site have metastases to gallbladder
● Most common are melanoma and lung cancer

Gross images
=========================================================================



Metastatic melanoma

Micro images
=========================================================================



Metastatic melanoma: H&E, HMB45



Malignant gallbladder tumors

Mucinous tumors


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Very uncommon

Case reports
=========================================================================

● 83 year old Japanese man with mucinous tumor and separate nodule of anaplastic carcinoma (Arch Pathol Lab Med 1999;123:1280)

Gross images
=========================================================================



Mucinous tumor with separate tumor nodule of anaplastic carcinoma


Poorly differentiated mucinous adenocarcinoma invading liver

Micro images
=========================================================================



Columnar epithelium producing abundant mucin



Malignant gallbladder tumors

Sarcoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Primary gallbladder sarcoma is rare (Am J Surg Pathol 2009;33:826)
● MFH is most common, then leiomyosarcoma, rarely angiosarcoma
● Older female adults who usually present with acute cholecystitis, abdominal pain, weight loss, pruritus, leukocytosis, elevated alkaline phosphatase and bilirubin
● Overall poor prognosis (Dig Dis Sci 2009;54:395), except botryoid embryonal RMS (young children), which may have excellent prognosis

Differential diagnosis
=========================================================================

Carcinosarcoma
Melanoma
Sarcomatoid / spindle cell carcinoma: keratin+ / CK18+



Malignant gallbladder tumors

Sarcomatoid carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called spindle cell carcinoma, carcinosarcoma
● < 50 cases reported in gallbladder
● Usually elderly women
● Both components (spindled and epithelial) appear to be derived from single clone (Hum Pathol 2004;35:418)
● Usually death within 6 months of diagnosis

Case reports
=========================================================================

● 59 year old woman (BMJ Case Rep 2011 Apr 1;2011)
● 61 year old woman with tumor containing rhabdoid component (Arch Pathol Lab Med 2003;127:e406)

Gross description
=========================================================================

● Polypoid, firm, solid, yellow-gray, granular with necrosis

Gross images
=========================================================================



Courtesy of Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina

Micro description
=========================================================================

● Malignant epithelial and sarcomatous components
● Neoplastic glands contain mucin or rarely include squamous cell carcinoma
● Sarcomatous component consists of pleomorphic or spindle cells, sometimes with heterologous osteosarcoma, chondrosarcoma or rhabdomyosarcoma

Micro images
=========================================================================



Tumor with rhabdoid component, CK+, vimentin+






Courtesy of Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina

Positive stains
=========================================================================

● Cytokeratin and EMA in both components
● CEA in epithelial component



Malignant gallbladder tumors

Small cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare high grade neuroendocrine carcinoma resembling tumor of lung
● Mean age 69 years, slight female predominance
● 75% had local extension or metastasis at surgery
● 50% had other coexisting neoplasms, usually adenocarcinoma (Am J Surg Pathol 2001;25:595)
● Mean survival 11 months, range 3-25 months, 10 year survival is zero (Ann Diagn Pathol 2009;13:378)
● No systemic endocrine symptoms

Case reports
=========================================================================

● 54 year old woman with a history of HIV/AIDS (Gastrointest Cancer Res 2011;4:135)

Gross description
=========================================================================

● Mean 3 cm

Micro description
=========================================================================

● Sheets of small cells with hyperchromatic nuclei, finely stippled chromatin, inconspicuous nucleoli, nuclear molding, Azzopardi phenomenon (basophilic staining of blood vessel walls by DNA deposition), scant cytoplasm
● May have minor component of tumor cells in trabeculae, nests or ribbons
● Frequent mitotic activity, necrosis and apoptosis
● Invasion of muscularis propria and perimuscular connective tissue in 90%

Micro images
=========================================================================



H&E, pRB, p16


High N/C ratio, high mitotic rate, nuclear molding, and negative RB staining in tumor cells compared to intact staining in adjacent endothelial cells

Cytology images
=========================================================================



Small round malignant cells

Positive stains
=========================================================================

● AE1-AE3, CAM5.2, chromogranin, NSE, Leu7/CD57, CEA (25%)

Electron microscopy description
=========================================================================

● Dense core secretory granules

Molecular description
=========================================================================

● p53 (75%), p16 INK4a (33%), K-ras codon 12 abnormalities (17%)
● No DPC4 mutations



Malignant gallbladder tumors

Squamous cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 October 2014, last major update September 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Typically diagnosed late, and have poor prognosis (Cir Esp 2007;81:202)

Gross images
=========================================================================



Tumor encasing gallstones and invading liver

Micro description
=========================================================================

● Cords, islands, sheets of malignant squamous cells separated by dense fibrous stroma
● Anaplastic to well-differentiated, keratinizing tumors

Micro images
=========================================================================



Squamous cell carcinoma



Miscellaneous

TNM staging for Carcinoma of gallbladder and cystic duct


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Classification excludes sarcomas and carcinoid tumors

Primary tumor (T) - carcinoma of gallbladder and cystic duct
=========================================================================

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor invades lamina propria or muscular layer
T1a: Tumor invades lamina propria
T1b: Tumor invades muscular layer
T2: Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver
T3: Tumor perforates the serosa (visceral peritoneum) or directly invades the liver or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum or extrahepatic bile ducts
T4: Tumor invades main portal vein or hepatic artery or invades two or more extrahepatic organs or structures

Regional lymph nodes (N) - carcinoma of gallbladder and cystic duct
=========================================================================

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis to nodes along the cystic duct, common bile duct, hepatic artery or portal vein
N2: Metastases to periaortic, pericaval, superior mesenteric artery or celiac artery lymph nodes

Distant metastasis (M) - carcinoma of gallbladder and cystic duct
=========================================================================

M0: No distant metastasis
M1: Distant metastasis

Stage grouping- carcinoma of gallbladder and cystic duct
=========================================================================

0: Tis N0 M0
I: T1 N0 M0
II: T2 N0 M0
IIIA: T3 N0 M0
IIIB: T1-3 N1 M0
IVA: T4 N0-1 M0
IVB: any T N2 M0 or any T any N M1


Table

Pathologic Staging (pTNM)
=========================================================================

TNM Descriptors (required only if applicable) (select all that apply)
___ m (multiple primary tumors)
___ r (recurrent)
___ y (posttreatment)



Miscellaneous

Frozen section


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Optimally should have clinical data and serum AFP levels available
● Should know if specimen is from a mass
● Indication: presence of a polypoid mucosal lesion or a suspicious thickening of the gallbladder wall (Arch Pathol Lab Med 2005;129:1610)

Gross images
=========================================================================



Carcinoma



Miscellaneous

Grossing


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Sample tumor thoroughly, margins, normal bile duct

Larger masses/carcinoma:
● Submit several full thickness sections, including areas of deepest penetration
● Cystic duct margin, hepatic margin, extent of penetration into liver (if applicable)



Miscellaneous

Features to report


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Tumor size and location
● Tumor histologic type and pattern
● Depth of invasion
● Number and size of tumor nodules
● Tumor extension to adjacent structures
● Status of resection margins (cystic duct, liver bed, other)
● Cystic duct involvement
● Liver bed involvement
● Regional lymph nodes: number identified, number with tumor
● Angiolymphatic invasion
● Perineural invasion
● Presence of carcinoma in situ or dysplasia

Additional pathologic findings to report:
● Chronic cholecystitis, metaplasia (squamous, pyloric gland, intestinal metaplasia), inflammatory bowel disease, porcelain gall bladder, presence or absence of stones (gallbladder cancer occurring without stones may be caused by anomalous choledocho-pancreatic junction or associated with chronic inflammatory bowel disease, Arch Pathol Lab Med 2000;124:37)

End of Gallbladder > Superpage


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