Bile Duct Tumors Workup
- Author: Todd A Nickloes, DO, FACOS; Chief Editor: John Geibel, MD, DSc, MSc, AGAF more...
Results of liver function tests (LFTs) are suggestive of cholestasis in patients with bile duct tumors. Fluctuations in serum levels reflect incomplete obstruction or primary involvement of only one hepatic duct. In complete obstruction, serum bilirubin is markedly elevated. Serum alkaline phosphatase and gamma glutamyl transferase also are markedly elevated because they are markers of bile duct injury. Serum aspartate aminotransferase and alanine aminotransferase, which mark hepatocellular damage, usually are only mildly elevated.
Patients usually are anemic. The leukocyte count may be high normal, with a preponderance of polymorphs. Levels of serum CEA and alpha-fetoprotein (AFP) usually are normal and not elevated. A serum mitochondrial antibody test also produces negative results.
Feces are pale and fatty, with occasional blood.
Ultrasonographic scanning of the liver is the investigation of first choice in patients with obstructive jaundice; these scans usually reveal dilated intrahepatic biliary ducts. The extrahepatic duct may be collapsed if the tumor is high (eg, a Klatskin tumor at the bifurcation). A tumor mass may be observed in 40% of cases as a hyperechoic lesion. The absence of dilatation of intrahepatic bile ducts suggests an alternate diagnosis, such as drug-related jaundice or primary biliary cirrhosis.
Computed tomography (CT) of the abdomen demonstrates intrahepatic biliary dilatation and lobar atrophy, but tumor mass may be difficult to demonstrate. Calcification may be observed. CT is useful in diagnosing the level of obstruction in nearly all patients, and a specific diagnosis is possible in 78% of patients. Spiral (helical) CT allows accurate analysis of the relation between vascular and bile duct anatomy at the hilum.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) of the abdomen may be performed, but it adds little to ultrasonography and CT with respect to establishing the diagnosis of extrahepatic cholangiocarcinoma. MRI cholangiography may be valuable and is increasingly available in specialized centers.[12, 13, 14]
Angiography and cholangiography
Digital subtraction angiography (DSA) is useful in the preoperative assessment of resectability and demonstrates the anatomy of the hepatic artery and portal vein.
Cholangiography is indicated in any patient who is cholestatic with nondilated bile ducts when the diagnosis is in doubt. The choice of cholangiographic investigation depends on the site of the tumor.
In proximal lesions, percutaneous transhepatic cholangiography (PTC) defines the extent of the tumor and allows the preoperative placement of percutaneous catheters.
Endoscopic retrograde cholangiopancreatography (ERCP) is of greater value in the diagnosis of distal tumors and permits the placement of endoprostheses (see the image below).
Presenting patterns of cholangiocarcinoma
Radiologically, cholangiocarcinomas present in three distinct patterns, as follows.
An intrahepatic mass is observed in 20-30% of cases. Calcification may be present. Ultrasonography reveals a hypoechoic, hyperechoic, or mixed echogenicity mass, whereas CT reveals a low-density, heterogeneous, and often peripherally enhancing mass.
A hilar Klatskin tumor is the most common pattern. Ultrasonography and CT of the abdomen show intrahepatic biliary dilatation with a normal-appearing cystic duct and hilar mass. In addition, segmental or lobar atrophy may exist. Portal and retroperitoneal adenopathy also are common. Cholangiography is diagnostic, with a stricture observed straddling the bifurcation and isolated right and left systems.
The distal duct form presents as a stricture and (less commonly) as a polypoid-filling defect. The stricture may be irregular, with overhanging edges suggestive of a malignant stricture, or it may be smooth and indistinguishable from benign strictures.
Tissue diagnosis can be obtained by means of percutaneous fine-needle aspiration (FNA) biopsy, brush-and-scrape biopsy, or cytologic examination of bile.[17, 18] However, these techniques provide a definitive diagnosis in only 30-50% of patients. If surgery is contemplated, preoperative tissue diagnosis is not essential, and surgical exploration is indicated.
A bile duct tumor is typically quite small (see the image below); 95% are adenocarcinomas of varying differentiation. Grossly, the tumor may be nodular or papillary or may present as a stricture (scirrhous variety).
Nodular bile duct tumors form extraductal nodules in addition to intraluminal projections. The papillary variety most commonly is found in the distal bile duct and may fill the duct lumen with friable, vascular neoplastic tissue, which may cause hemobilia. The scirrhous variety usually is confined to the hilar area and forms gray, annular thickenings with clear defined edges. Distinguishing this variant from sclerosing cholangitis occasionally is difficult, even on histologic grounds.
Microscopically, the tumor usually is a mucin-secreting adenocarcinoma with a cuboidal or columnar epithelium, and spread along neural sheaths may be noted. The scirrhous variety is intensely fibrotic and relatively acellular, often with a few well-differentiated ductal cancer cells grouped as acini in a dense connective-tissue stroma. Rare types include squamous cell carcinoma, adenosquamous carcinoma, adenoacanthoma, mucoepidermoid carcinoma, cystadenocarcinoma, granular cell carcinoma, lymphoma, carcinoid tumors, and melanoma. Malignant smooth-muscle tumors of the bile duct and nonsecreting apudomas of the hilar region also have been reported.
Immunohistochemistry and molecular biological studies show that in addition to CEA, many tumors also stain positively for the carbohydrate antigens CA 50 and CA 19-9. Some reports also have identified mutations in K-ras oncogenes in 60-70% of intrahepatic and perihilar bile duct cancers. Further studies have identified abnormalities on chromosomes 5 and 17 and have documented the presence of c-erb oncogenes, epidermal growth factors, and proliferating nuclear antigens.[3, 19]
The diagnosis of bile duct cancers may be supported by positive findings in two of the following three indicators:
Positive reaction to CEA
Nuclear size variation
Formation of distended intracytoplasmic lumina
Neural invasion is another histologic finding that confirms a diagnosis of bile duct cancer.
Bile duct tumors are staged according to the tumor-node-metastasis (TNM) system of classification developed by the American Joint Comittee on Cancer (AJCC). Three different classification schemas are used, depending on the location of the tumor, as follows :
Intrahepatic bile duct tumors
Perihilar bile duct tumors
Distal bile duct tumors
For more information, see Biliary Tract Cancer Staging.
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