Types of Cancers

More than 80% of all cancers of the gallbladder and bile ducts are carcinomas: tumors that arise in the epithelium (or surface lining).

Because most of the carcinomas produce small spaces (called glands), they are more specifically classified as "adenocarcinomas." Another term specifically used for these carcinomas is "cholangiocarcinoma" because of their origin from the biliary tract. Most biliary tract adenocarcinomas are highly invasive cancers that penetrate deeply into the walls of the bile duct or gallbladder. A smaller proportion of these adenocarcinomas tends to grow superficially into the open spaces (lumen) of the biliary tract as frond-like, "papillary" tumors. These papillary tumors are less likely to invade deeply, and therefore tend to have a better prognosis. Other more rare carcinomas of the biliary tree include small cell (neuroendocrine) carcinoma, and adenosquamous carcinoma.

Other tumor types rarely affect the biliary tract. Rare cases of malignant melanoma, a tumor that usually arises from the skin, and malignant lymphoma, that usually arises in the lymph nodes, can originate from the biliary tract or its surrounding tissues. It is important to distinguish these cancers from usual biliary carcinomas, since their treatment is different. Children almost never develop carcinomas of the biliary tree. The most common malignant tumor of the biliary tree in children is rhabdomyosarcoma, a tumor of the wall of the extrahepatic bile ducts (not its lining) which forms primitive skeletal muscle.

Biliary tract carcinomas are also often separated by location into carcinoma of the gallbladder and carcinoma of the extrahepatic (outside the liver) and intrahepatic (inside the liver) bile ducts.

Gallbladder carcinoma is twice as common as carcinoma of the extrahepatic bile ducts (5000 cases per year versus 2500 per year in the USA). Patients are usually in their 60's when they first show signs of disease, and there is a slight female predominance. This likely relates to the fact that the main risk factor for gallbladder carcinoma is gallstones (cholelithiasis), and these are more common in females. Gallstones are present in over 80% of gallbladders containing gallbladder carcinoma. The risk of developing carcinoma is increased if the stones are large and symptomatic, so these gallstones are generally removed prophylactically (for the purpose of preventing subsequent cancer) by surgery. The risk to each individual patient with asymptomatic gallstones is small; therefore, not all patients with gallstones necessarily need to have them removed.

Other risk factors for gallbladder cancer include:

• Calcification of the gallbladder wall, which is often associated with gallstones and creates a "porcelain gallbladder" when severe

• Benign polyps (noncancerous growths of the surface epithelium) of the gallbladder

• Chronic bacterial infections of the biliary tract, which can predispose to gallbladder carcinoma, particularly in Asia, where gallstones are infrequent

1. History of Primary Sclerosing Cholangitis (PSC) -- this is thought to be an autoimmune disorder, one in which the body's own inflammatory cells attack the bile ducts. PSC causes progressive scarring and narrowing of the bile ducts, which block bile from reaching the intestines. Many patients eventually develop liver failure, necessitating liver transplant. 10-20% of patients with PSC will develop bile duct carcinoma. Walter Payton, the Chicago Bears Hall of Fame football player, appears to have died from a bile duct cancer which developed after he was diagnosed with PSC. It is thought that the progressive epithelial injury and subsequent regeneration predisposes patients with PSC to carcinoma. More than half of patients with PSC have a history of another autoimmune disorder, idiopathic inflammatory bowel disease. This is most often ulcerative colitis.
   
   
2. Congenital abnormalities (abnormalities one is born with) of the bile ducts -- these include choledochal cysts (dilation of the common bile duct) and Caroli's disease (dilation of the intrahepatic bile ducts). It is thought that prolonged sludging of bile in these dilated spaces and subsequent infection predispose patients to carcinoma, again through progressive epithelial injury and repair. The overall lifetime risk of cholangiocarcinoma in these patients is 10%.
   
   
3. Benign tumors of the bile ducts -- A major risk factor is biliary papillomatosis, which refers to multiple papillary tumors diffusely involving the bile ducts. These may progress to invasive carcinoma.
   
   
4. Hepatobiliary parasitic infection -- these cases are most often seen in the Far East and include Clonorchis sinensis (most prevalent in Japan, Korea, Vietnam) and Opisthorchis viverrini (most prevalent in Thailand, Laos, Malaysia). Clonorchis is acquired when humans eat fresh water fish that harbor the Clonorchis cyst. The cysts develop into flukes (flatworms) in the friendly confines of the human intestine, and ascend from the duodenum (the first part of the intestine) into the common bile duct where they mature. The worms grow to be approximately 1 cm in length, and have a sucker that allows them to attach to the bile duct epithelium. Constant irritation of the biliary tract epithelium leads to epithelial damage, denudation (loss of the epithelial lining) and regeneration with fibrosis (production of collagen, or scar tissue). Carriage of this worm imparts a 25-50-fold risk of developing biliary tract carcinoma.
   
   
5. Toxic exposures -- thorium dioxide (Thorotrast), used as a contrast dye in radiologic procedures between 1930-1950, has been shown to promote cancers in the liver and bile ducts.