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Extrahepatic bile ducts

Tumors

Carcinoma of extrahepatic bile ducts


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
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● Rare (1 per 100,000 in US); 90-95% of extrahepatic bile duct malignancies are adenocarcinomas (bile duct carcinoma, cholangiocarcinoma)
● Present in 0.5% of autopsies
● 2-3 times less common than gallbladder carcinoma

Clinical features
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● More common in Native Americans, Mexicans, Israelis, Japanese
● Present with painless, progressive jaundice; 1/3 have gallstones (10% in bile ducts themselves), 20% had prior biliary tract surgery
● Usually age 60+; rare before age 40 unless have risk factors below
● Small at diagnosis because even small tumors cause obstruction and jaundice

Risk factors:
Clonorchis sinensis and Opisthorchis viverrini infestations, primary sclerosing cholangitis, chronic ulcerative colitis, choledochal cysts, Caroliís disease, congenital hepatic fibrosis
● Also cystic fibrosis, familial polyposis coli, chronic typhoid carriers, biliary giardiasis, Thorotrast exposure, pancreaticobiliary maljunction (PBM) with bile duct dilatation (J Hepatobiliary Pancreat Surg 2008;15:15)

Spread and metastases:
● Local extension to ampulla of Vater, colon, duodenum, gallbladder, liver, omentum, pancreas, stomach
● Tumors from right or left hepatic duct usually extend proximally into liver or distally to common hepatic duct
● Tumors from cystic duct extend to gallbladder or common bile duct
● Tumors from distal common bile duct extend to pancreas, duodenum, stomach, colon, omentum
● Metastases to regional lymph nodes, liver, lungs, peritoneum

Klatskin (hilar) tumors
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● 70% of tumors
● Arise at confluence of right and left hepatic ducts at liver hilus
● Slow growing with infrequent distant metastases, have marked sclerosing characteristics
● Poorer prognosis since difficult to resect
● 28-89% have positive margins

Diagnosis
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● Tissue diagnosis is optimal because clinical diagnosis is often incorrect
● Also brushings, bile drainage cytology

Laboratory
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● Elevated alkaline phosphatase but normal serum bilirubin suggests location above hepatic duct bifurcation or incomplete common bile obstruction

Prognostic factors
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● Presence of intraepithelial spread is not an indicator of a poor prognosis, but carcinoma in situ at the bile duct stump can cause recurrence (Mod Pathol 2008;21:807)
● Mean survival 6-18 months, 2 years if resectable
● 5 year survival is only 5%, but is 60% for T1 tumors (which are rare)

Favorable:
● Low stage, papillary histology, lack of metallothionein expression (Hum Pathol 2009;40:1706), distal tumors, CDX2 and MUC2 (Am J Clin Pathol 2005;124:361)

Unfavorable:
● High grade or high stage tumors, positive surgical margins, hilar tumors, decreased expression of focal adhesion kinase (Hum Pathol 2010;41:859), IMP3 expression (Hum Pathol 2009;40:1377), nuclear KIT expression (Mod Pathol 2007;20:562)
● Presence of tumor necrosis in the nodal tumors, severe nuclear atypia of the tumor cells in lymph vessels (Hum Pathol 2005;36:655)

Case reports
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● 42 year old Japanese woman with obstructive jaundice (Acta Med Okayama 2010;64:63)

Treatment
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● Klatskin tumors require resection of hepatic duct bifurcation
● Distal tumors may require Whipple procedure

Gross description
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● Either firm, gray nodules within bile duct wall or diffusely infiltrative (2%)
● Often extends into adjacent structures
● Limits of tumor often difficult to detect due to desmoplasia
● Tumors may be papillary, multifocal and friable

Gross images
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Bile duct carcinoma

Micro description
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● Nodular or diffusely infiltrative tumors with marked desmoplastic response
● Sclerosing, nodular, polypoid-papillary or mixed types
● Resembles gallbladder carcinoma
● Most are well or moderately differentiated with conspicuous glands, but have extensive perineural invasion
● Even well differentiated tumors may have poorly differentiated foci deep within wall
● Mucin always present within tumor cells and glandular lumina
● Tumor cells cuboidal or columnar, with vesicular nuclei and prominent nucleoli
● Usually angiolymphatic invasion, necrosis and chronic inflammatory infiltrate
● Often adjacent intestinal and pylori metaplasia
● Dysplasia usually present
● Variants include adenosquamous, clear cell, colloid, mucoepidermoid, small cell, squamous cell, undifferentiated (pleomorphic, sarcomatoid, giant cell) carcinomas
● Pyloric gland phenotype involves younger patients, usually well differentiated tumors with characteristic stellar pattern, extensive perineural invasion, MUC6+ and MUC5AC+ (Hum Pathol 2012;43:2292)
● Diagnostically difficult cases are extremely well differentiated, but still have thickened duct wall with prominent desmoplastic response and perineural invasion

Micro images
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Choledochal duct adenocarcinoma


Adenocarcinoma of the gallbladder

Virtual slides
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Moderately differentiated adenocarcinoma

Positive stains
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● Mucin, CEA, CK7 (Am J Surg Pathol 2000;24:870, Arch Pathol Lab Med 2000;124:1196), P-cadherin and CD24 (Hum Pathol 2010;41:1558), EGFR (Hum Pathol 2010;41:485)

Negative stains
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● CK20, CD10 (Am J Surg Pathol 2012;36:101, Histopathology 2009;55:423)

Molecular
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● Promoter hypermethylation is important mechanism in inactivation of p16 gene (Arch Pathol Lab Med 2006;130:33)
● Telomere shortening has been observed in dysplastic epithelium and invasive adenocarcinomas of biliary tract (Mod Pathol 2006;19:772)

Differential diagnosis
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● Intraductal spread of hepatocellular carcinoma, cholangiocarcinoma, metastatic carcinoma
● Metastatic carcinoma: breast, colon, ovary, kidney
● Spread from adjacent tumors of ampulla, colon, duodenum, gallbladder, liver, pancreas, stomach
Sclerosing cholangitis: no perineural invasion, no random glandular infiltration

End of Extrahepatic bile ducts > Tumors > Carcinoma of extrahepatic bile ducts


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