Cholangiocarcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Catherine Forse MD FRCPC
April 22, 2026

Cholangiocarcinoma is a cancer that starts in the bile ducts — the network of small tubes that carries bile from the liver and gallbladder to the small intestine, where bile helps digest fats. It is sometimes called bile duct cancer. Cholangiocarcinoma can begin anywhere along this network, and where the cancer starts has an important effect on the symptoms it causes, how it is treated, and the outlook.

This article provides an overview of cholangiocarcinoma as a group of cancers. It explains the different types based on location, the most common causes and symptoms, how the diagnosis is made, and what to expect after diagnosis. Because the details vary significantly by location, each type has its own, more detailed article linked below.

Types of cholangiocarcinoma

Cholangiocarcinoma is divided into three main types based on where in the bile duct system the tumor starts. This distinction matters because each type tends to behave and be treated differently and may have distinct molecular features.

Intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma starts in the small bile ducts within the liver. It accounts for approximately 20% of cholangiocarcinomas and often grows silently as a mass within the liver before causing symptoms. Because it usually forms a tumor rather than blocking a duct, it is often discovered only once it has become relatively large. Treatment decisions depend heavily on whether the tumor can be removed surgically and on the results of molecular testing, which frequently identifies targetable changes such as FGFR2 fusions or IDH1 mutations. For a detailed discussion, see our article on intrahepatic cholangiocarcinoma.

Perihilar cholangiocarcinoma

Perihilar cholangiocarcinoma — sometimes called a Klatskin tumor — starts at the junction where the right and left hepatic ducts meet as they leave the liver. It is the most common type, accounting for roughly half of all cholangiocarcinomas. Because it develops at a critical junction point, it often causes blockage of bile flow and jaundice relatively early, which can make it easier to detect than intrahepatic tumors. Perihilar cholangiocarcinoma is one of the two forms of extrahepatic cholangiocarcinoma and is covered in our article on extrahepatic cholangiocarcinoma.

Distal cholangiocarcinoma

Distal cholangiocarcinoma starts in the lower part of the common bile duct, near where it enters the small intestine. It accounts for about 30% of cholangiocarcinomas and, like perihilar tumors, tends to cause jaundice early because of its location. Because the tumor sits near the head of the pancreas, it can closely resemble pancreatic cancer on imaging and is often treated with the same type of surgery (the Whipple operation). Distal cholangiocarcinoma is the second form of extrahepatic cholangiocarcinoma and is also covered in our article on extrahepatic cholangiocarcinoma.

What causes cholangiocarcinoma?

Cholangiocarcinoma is strongly linked to long-standing inflammation or damage to the bile ducts. Years of repeated injury, inflammation, and repair cause genetic changes to accumulate in the cells that line the ducts, and over time a small number of these cells can begin to grow in an uncontrolled way.

Known risk factors include:

• Primary sclerosing cholangitis — A chronic disease that causes scarring and narrowing of the bile ducts and is the strongest known risk factor in North America and Europe.
• Chronic viral hepatitis — Hepatitis B and hepatitis C, particularly as risk factors for intrahepatic cholangiocarcinoma.
• Cirrhosis — Long-standing liver scarring from any cause, which also increases the risk of intrahepatic cholangiocarcinoma.
• Bile duct cysts and congenital abnormalities — Structural differences in the bile ducts present from birth, such as choledochal cysts.
• Chronic bile duct blockage or infection — Long-standing obstruction from gallstones or recurrent bacterial cholangitis.
• Liver fluke infections — Parasitic infections with Opisthorchis viverrini or Clonorchis sinensis, common in parts of Southeast Asia, that chronically injure the bile ducts.
• Other factors — Smoking, chronic pancreatitis, certain metabolic conditions (including obesity and type 2 diabetes), and rare occupational chemical exposures.

In many people, no clear cause is identified. Cholangiocarcinoma is most often diagnosed in people in their 60s or 70s and affects men and women at roughly equal rates.

What are the symptoms of cholangiocarcinoma?

Symptoms depend on where the tumor starts. Perihilar and distal cholangiocarcinomas tend to block bile flow early and therefore cause noticeable symptoms while the tumor is still relatively small. The most common of these is jaundice — yellowing of the skin and the whites of the eyes — which may worsen quickly or come and go. Other symptoms linked to bile duct blockage include itching, dark urine, pale or greasy stools, and cholangitis, an infection of the blocked ducts that causes fever and chills.

Intrahepatic cholangiocarcinomas grow within the liver and often do not block bile flow until late, so they may grow silently for a long time. When symptoms do occur, they tend to be non-specific — pain or discomfort in the right upper abdomen, unintentional weight loss, loss of appetite, and fatigue.

How is the diagnosis made?

The diagnosis of cholangiocarcinoma is usually made using a combination of imaging, procedures to obtain tissue or cell samples, and examination of the samples under the microscope by a pathologist. Imaging studies such as MRI with MRCP, CT, ultrasound, and PET scans are used to locate the tumor, measure its size, assess spread, and determine whether it can be removed with surgery. Blood tests are often abnormal, showing elevated liver enzymes and bilirubin, and the tumor marker CA 19-9 is frequently elevated.

How tissue is obtained depends on where the tumor is located. For intrahepatic tumors, a sample is usually obtained by a needle biopsy through the skin under ultrasound or CT guidance. For perihilar and distal tumors, samples are usually collected during endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound (EUS), often using a small brush advanced into the bile duct to scrape cells. These endoscopic procedures also allow the placement of a stent to relieve bile duct blockage at the same time.

Under the microscope, most cholangiocarcinomas are adenocarcinomas, meaning they form abnormal gland-like structures. The glands are typically irregular and surrounded by dense scar tissue called desmoplastic stroma. The tumor cells often invade surrounding tissues, grow along nerves, and enter blood vessels and lymphatic channels. Pathologists also look for precancerous changes in the nearby bile duct lining, including biliary intraepithelial neoplasia, which supports the idea that the cancer developed gradually over time. In some cases, immunohistochemistry or molecular testing is needed to distinguish cholangiocarcinoma from other cancers that can look similar, such as hepatocellular carcinoma or adenocarcinomas that have spread to the liver from another site.

Biomarker and molecular testing

Molecular testing has become an important part of the evaluation of cholangiocarcinoma, particularly for advanced or recurrent disease. Current guidelines recommend comprehensive molecular profiling — usually by next-generation sequencing — for anyone with advanced biliary tract cancer, because a growing number of targeted treatments are available when a specific genetic change is found. The relevant biomarkers differ by type:

• FGFR2 fusions — Most common in intrahepatic cholangiocarcinoma. Treated with FGFR inhibitors such as pemigatinib or futibatinib.
• IDH1 mutations — Most common in intrahepatic cholangiocarcinoma. Treated with ivosidenib.
• HER2 amplification or overexpression — More common in extrahepatic (perihilar and distal) and gallbladder cancers. Treated with HER2-directed therapies such as zanidatamab, trastuzumab plus pertuzumab, or tucatinib plus trastuzumab.
• BRAF V600E — Uncommon, but when present, can be treated with dabrafenib plus trametinib under a tumor-agnostic approval.
• NTRK fusions — Rare, but when present, can be treated with larotrectinib or entrectinib.
• Mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) — Uncommon, but when present, makes the tumor eligible for pembrolizumab. It may also indicate Lynch syndrome and should prompt genetic counseling.

For more information about these and other biomarkers, visit the Biomarkers section.

What is the prognosis?

The outlook for cholangiocarcinoma depends mainly on where the tumor started, whether it can be completely removed by surgery, the stage at diagnosis, and the microscopic features of the tumor. Perihilar and distal tumors tend to be detected earlier because they cause symptoms sooner, but they occur in anatomically complex areas where complete surgical removal can be difficult. Intrahepatic tumors are often larger at diagnosis but can sometimes be removed with a partial liver resection or treated with local therapies such as ablation or radiation.

For patients whose tumors can be completely removed by surgery, five-year survival ranges from approximately 20 to 40%, depending on the type. Survival is substantially lower when the tumor cannot be removed or has already spread. Modern chemotherapy combined with immunotherapy has extended average survival for advanced disease to approximately 12 to 15 months, and targeted therapies can provide meaningful benefit for patients whose tumors carry specific genetic changes.

Detailed prognostic information for each type is covered in the subtype-specific articles.

What happens after the diagnosis?

Care for cholangiocarcinoma is usually coordinated by a multidisciplinary team that includes a hepatobiliary surgeon, a medical oncologist, a radiation oncologist, an interventional radiologist, and a gastroenterologist. Treatment decisions depend on where the tumor is located, how far it has spread, the patient’s overall health, and the results of molecular testing.

When the tumor can be surgically removed, the type of operation depends on location — partial liver resection for intrahepatic tumors, resection of the affected bile duct along with part of the liver for perihilar tumors, or a pancreaticoduodenectomy (Whipple operation) for distal tumors. Chemotherapy with capecitabine is often given after surgery to reduce the risk of recurrence. When surgery is not possible, first-line treatment for advanced disease is typically a combination of chemotherapy (gemcitabine and cisplatin) with immunotherapy (durvalumab or pembrolizumab). Patients whose tumors carry targetable genetic changes may be eligible for specific targeted therapies either upfront or after initial treatment. Relief of bile duct blockage with a stent is often needed to treat jaundice and prevent infection.

Follow-up after treatment usually includes regular imaging and blood tests, including the tumor marker CA 19-9. Treatment of any underlying liver or bile duct condition — such as primary sclerosing cholangitis, viral hepatitis, or metabolic liver disease — continues to be important throughout, because ongoing injury to the bile ducts can increase the risk of new tumors.

Questions to ask your doctor

• Where exactly did my cancer start — in the bile ducts inside the liver (intrahepatic), at the junction of the hepatic ducts (perihilar), or in the lower common bile duct (distal)?
• Which subtype-specific article should I read to learn more about my diagnosis?
• Can the tumor be completely removed by surgery?
• What is the pathologic stage of my cancer?
• Has my tumor been tested for FGFR2 fusions, IDH1 mutations, HER2, BRAF, NTRK fusions, and mismatch repair status?
• Are any of my molecular test results actionable with a targeted treatment?
• What role will chemotherapy, immunotherapy, or radiation therapy play in my treatment?
• Am I a candidate for a clinical trial?
• Do I need a stent to relieve bile duct blockage?
• Do I have an underlying liver or bile duct condition — such as primary sclerosing cholangitis, viral hepatitis, or cirrhosis — that should be managed at the same time?
• What is the plan for follow-up imaging and CA 19-9 testing?
• Should any of my family members be screened, particularly if Lynch syndrome is a possibility?