Gallbladder & extrahepatic bile ducts
Extrahepatic bile duct nonneoplastic and tumors
Carcinoma of extrahepatic bile ducts
Author: Hanni Gulwani, M.B.B.S.
Last author update: 1 September 2012
Last staff update: 21 November 2023 (update in progress)
Copyright: 2003-2023, PathologyOutlines.com, Inc.
PubMed Search: Carcinoma extrahepatic bile ducts
Table of Contents
Definition / general | Clinical features | Klatskin (hilar) tumors | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosisCite this page: Gulwani H. Carcinoma of extrahepatic bile ducts. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/gallbladdercarcinomaextrahepatic.html. Accessed November 29th, 2023.
Definition / general
- Rare (1 per 100,000 in U.S.); 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
- 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, Caroli 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
- 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
- Tissue diagnosis is optimal because clinical diagnosis is often incorrect
- Also brushings, bile drainage cytology
Laboratory
- Elevated alkaline phosphatase but normal serum bilirubin suggests location above hepatic duct bifurcation or incomplete common bile obstruction
Prognostic factors
- 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
- 42 year old Japanese woman with obstructive jaundice (Acta Med Okayama 2010;64:63)
Treatment
- Klatskin tumors require resection of hepatic duct bifurcation
- Distal tumors may require Whipple procedure
Gross description
- 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
Images hosted on other servers:
Bile duct carcinoma
Microscopic (histologic) description
- 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
Microscopic (histologic) images
Contributed by Andrey Bychkov, M.D., Ph.D.
Adenocarcinoma
Images hosted on other servers:
Choledochal duct adenocarcinoma
Positive stains
- 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
Molecular / cytogenetics description
- 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
- 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
