What Is the Difference Between Gallbladder Cancer and Cholangiocarcinoma?

Gallbladder cancer and cholangiocarcinoma are two different forms of biliary tract cancer. They affect the same bodily system and cause similar symptoms but may require different treatments.

Depending on where a tumor develops in the biliary tract, it may be gallbladder cancer or bile duct cancer, also known as cholangiocarcinoma.

The biliary tract is a network of tubes, or bile ducts, extending from the liver to the gallbladder and then the intestines. Its components produce, store and release bile into the intestine to aid fat digestion.

What Is Gallbladder Cancer?

Gallbladder cancer is a rare cancer in which malignant cells grow in the pear-shaped organ that stores and releases bile. The gallbladder has four layers:

• An inner layer containing moist mucosal tissue
• A muscle layer
• A connective tissue layer
• An outer layer

It usually begins in the inner layer and grows outward. According to the American Cancer Society (ACS), gallbladder cancer accounts for approximately 4 in every 10 biliary tract cancers.

A 2019 report identifies gallbladder cancer as the most common biliary tract cancer. It accounts for approximately 1.2% of cancer cases and 1.7% of cancer-related deaths worldwide. Almost all cases are adenocarcinomas, affecting fluid-secreting cells.

What Is Cholangiocarcinoma?

Cholangiocarcinoma is bile duct cancer. This network of tubes carries bile from the liver to the gallbladder and intestine, supporting its role in fat digestion.

Three types can develop:

• Extrahepatic cholangiocarcinoma: Occurs where the liver and gallbladder ducts join to form the common bile duct. It is also called distal cholangiocarcinoma. 
• Perihilar cholangiocarcinoma: Develops outside the liver where the right and left bile ducts leave it.
• Intrahepatic cholangiocarcinoma: A rare form occurring in bile ducts within the liver.

According to the ACS, approximately 8000 people are diagnosed annually in the United States.

What Are the Symptoms of Gallbladder and Bile Duct Cancers?

The United Kingdom's National Health Service (NHS) notes that symptoms of both cancers may be difficult to recognize or absent. 

Symptoms more often result from other health problems and may not immediately cause concern. However, persistent or worsening symptoms should prompt specialist assessment for possible cancer.

Gallbladder cancer generally causes no symptoms until advanced stages. According to the ACS, only one in 5 cases is detected before spread beyond the gallbladder.

Symptoms of gallbladder and bile duct cancer include:

• Jaundice, or yellowing of the eyes and skin, which may be less noticeable in people with darker skin
• Itchy skin
• Dark urine
• Pale stools
• Fever
• Weakness
• Chills
• An abdominal lump
• Digestive symptoms, including nausea and vomiting
• Loss of appetite
• Unintentional or unexpected weight loss
• Sharp or cramping abdominal pain
• Abdominal swelling unrelated to mealtimes

The NHS states that cholangiocarcinoma can cause the same symptoms as bile duct cancer.

What Causes These Two Cancers?

Cancer results from DNA errors that cause cells to multiply excessively. The direct causes of both cancers remain unclear. Many gallbladder cancer risk factors relate to chronic inflammation, which can arise from duct problems or gallstones.

Gallbladder Cancer Risk Factors

Major risk factors may include:

• Gallstones: Approximately 4 in 5 people with gallbladder cancer have gallstones at diagnosis.
• Porcelain gallbladder: A condition in which calcium deposits coat the gallbladder wall.
• Sex: In the United States, gallbladder cancer is 3–4 times more common in women than men.
• Obesity: Gallbladder cancer is more common in people with overweight or obesity.
• Age: It is more common in older people; the average age at diagnosis is 72.

Most people with gallstones never develop gallbladder cancer.

Cholangiocarcinoma Risk Factors

Bile duct cancers generally have no direct cause. However, certain conditions or environmental factors may increase risk. Factors include:

• Being older than 65
• Primary sclerosing cholangitis (PSC)
• Choledochal cysts, or rare enlargements of the bile ducts
• A liver parasite called a liver fluke that attacks the bile ducts, more common in Asia.
• Bile duct stones
• Past exposure to a medical contrast dye called Thorotrast
• Physical problems that may cause bile duct inflammation
• Gallbladder polyps
• Having typhoid

What Are the Treatment Options?

Surgery, radiation therapy and chemotherapy are the main treatments. Choices vary according to the extent of spread, cancer type and location.

Gallbladder Cancer Treatments

Options may include:

• Surgery to remove the gallbladder, surrounding tissue or nearby lymph nodes
• Radiation therapy
• Chemotherapy

However, gallbladder cancer is rarely detected early. For spread disease, specialists may use various operations to relieve obstruction, improve symptoms, clear blockages and drain accumulated fluid.

Cholangiocarcinoma Treatments

Depending on location, surgery may remove:

• The bile duct
• Part of the liver
• The bile duct, pancreatic head, gallbladder and parts of the stomach and small intestine through a Whipple procedure

After a Whipple operation, enough pancreas remains to continue producing insulin. People with perihilar cholangiocarcinoma may need liver transplantation. Radiation therapy or chemotherapy may be recommended afterward to destroy remaining cancer cells. 

Summary: Differences Between Gallbladder Cancer and Cholangiocarcinoma

These are rare biliary tract cancers that cause similar symptoms, including jaundice, abdominal pain, nausea and fever.

Gallstones are a common risk factor for gallbladder cancer. Other factors, including age over 65, choledochal cysts and primary sclerosing cholangitis, may increase the risk of both cancers.

Both may be treated with surgery, radiation therapy and chemotherapy. Procedures including liver or gallbladder stents and biliary bypass may help relieve symptoms. Surgery is more commonly used for cholangiocarcinoma, while treatment for advanced gallbladder cancer may begin with radiotherapy or chemotherapy.