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Histology of bile duct/gallbladder cancer

The gall bladder is a hollow organ that is covered by a single cell cubical epithelium, which is the origin of the majority of malignant tumors in this organ (adenocarcinoma).

Precursor lesions

Similar to many other carcinomas, the tumors in these organs often originate from precursor lesions. The nomenclature of precursor lesions has varied, though an international consensus conference has decided on the following terms; Extrahepatic and intrahepatic hilar bile ducts = biliary intraepithelial neoplasia grade I, II and III (BIL-IN I-III). This terminology is not well spread and not consistently used by pathologists. The terminology is used in the biliary ducts, not in the gallbladder. The precursor lesions are flat and not recognizable by radiological techniques. Brush cytology is a useful method to evaluate the precursor lesions in patients with primary sclerosing cholangitis.

In addition to flat intraepithelial precursor lesions there are also polyps. They represent papillary or tubular adenomas that can appear in all parts of extrahepatic ducts, but are predominately seen in the gall bladder. Transition into adenocarcinoma can be seen, but the risk is probably very low. On rare occasions, multicentric papillomatosis in the biliary ducts can be seen. The risk for developing adenocarcinomas is much higher in these instances. Cystadenomas similar to those in pancreas and liver can also appear in the biliary ducts. The risk of carcinoma is present and these lesions should be removed surgically.


Malignant tumors in the gall bladder and biliary ducts are almost exclusively adenocarcinomas. More specifically, they are classified as extrahepatic cholangiocarcinoma when the tumors originate from the extrahepatic ducts close to the hilum. Adenocarinomas originating from the distal part of ductus choledochus/ampulla Vateri can sometimes be difficult to separate from adenocarcinomas arising in the pancreas. The adenocarcinomas originating from extrahepatic biliary ducts are generally immunohistochemically positive for CK7 and negative for CK20.

However, there are variants of adenocarcinoma, including papillary adenocarcinoma (especially in the gall bladder), adenocarcinoma of intestinal type, mucinous adenocarcinoma (adenocarcinomas with > 50% mucin), clear cell adenocarcinoma and signet cell carcinoma (can give a linitis plastica appearance such as in the stomach).

Squamous cell carcinoma can appear, especially in the gall bladder with chronic cholecystitis with squamous cell metaplasia. Small cell carcinoma (poorly differentiated endocrine carcinoma) and undifferentiated carcinoma (in the gall bladder) can in rare cases appear.

Other malignant tumor

  • Endocrine tumors
  • Mesenchymal tumors
  • Lymphomas

These are very rare tumors in this localization.

Operation specimen handling

Cancer in the gall bladder is sometimes an accidental finding in cholecystectomy specimens from patients with cholecystitis. Cancer in the distal part of ductus choledochus is usually seen in a pancreaticoduodenectomy specimen (Whipple). In a few occasions with proximally located tumor, an exclusive resection of extrahepatic ducts with the gall bladder can be performed. The surgeon should mark the different resection borders using sutures in order for the pathologist to be able to orient the specimen correctly. The specimen must be well fixed in neutral buffered formalin as for all operation specimens.

Pathology report

Reports on operation specimens as for cholecystectomy and resection of extrahepatic biliary ducts should include the following information:

  • Tumor localization
  • Tumor size (largest diameter)
  • Histological type (WHO)
  • Grading
  • Infiltration depth
  • Resection borders
  • Blood vessel invasion
  • Perinneural infiltration
  • Lymph node metastasis
  • pTNM

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