Your pathology report for cholangiocarcinoma

by Jason Wasserman MD PhD FRCPC and Catherine Forse MD FRCPC
January 3, 2026

Cholangiocarcinoma is a type of cancer that starts in the bile ducts. Bile ducts are small tubes that carry bile from the liver to the intestine, where bile helps digest fats. This article focuses on extrahepatic cholangiocarcinoma, which means the cancer arises in the bile ducts outside the liver (for information on intrahepatic cholangiocarcinoma, see this article).

Extrahepatic cholangiocarcinoma is a serious condition, but it is often detected earlier than some other bile duct cancers because it commonly causes blockage of bile flow, leading to noticeable symptoms.

Where does extrahepatic cholangiocarcinoma develop?

Extrahepatic cholangiocarcinoma develops in the bile ducts outside the liver, including the common bile duct, and the hepatic ducts near where they exit the liver.

Tumours that arise at the junction of the right and left hepatic ducts are often called perihilar cholangiocarcinomas.

What are the symptoms of cholangiocarcinoma?

Most people are diagnosed in their 60s or 70s. Unlike gallbladder cancer, this disease affects men and women at similar rates.

Because these tumours block bile flow early, symptoms often appear while the tumour is still relatively small. The most common symptom is jaundice, which causes yellowing of the skin and eyes. Jaundice may worsen quickly or fluctuate over time.

Other symptoms can include itching, dark urine, pale stools, right upper abdominal pain, fatigue, loss of appetite, weight loss, nausea, and vomiting. If infection develops in the bile ducts (called cholangitis), fever and chills may occur and require urgent treatment.

What causes cholangiocarcinoma?

Cholangiocarcinoma is strongly associated with chronic inflammation of the bile ducts.

Known risk factors for cholangiocarcinoma include:

• Primary sclerosing cholangitis.

• Bile duct cysts and congenital bile duct abnormalities.

• Chronic bile duct blockage or infection.

• Parasitic infections in parts of Asia.

Other risk factors include smoking, certain metabolic conditions, chronic pancreatitis, and rare occupational chemical exposures. In many cases, no clear cause is identified.

How is cholangiocarcinoma diagnosed?

The diagnosis of cholangiocarcinoma usually involves a combination of imaging, endoscopic procedures, and pathology.

Imaging

Imaging tests such as MRI, CT, ultrasound, and PET scans help locate the tumour, determine its size, and assess whether it has spread. Typical imaging findings include:

• Blockage of the bile duct with dilation of the ducts upstream.

• Thickening of the bile duct wall.

• Abnormal enhancement of the duct on contrast imaging.

Imaging is also used to determine whether the tumour can be surgically removed.

Endoscopic procedures

Procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) allow doctors to examine the bile ducts, obtain samples directly, and place stents to relieve bile obstruction.

Microscopic (pathologic) features

When tissue is examined under the microscope, most extrahepatic cholangiocarcinomas are adenocarcinomas, meaning they form abnormal gland-like structures. These glands are often irregular and widely spaced, surrounded by dense scar tissue called desmoplastic stroma.

The tumour cells may invade surrounding tissues and commonly grow along nerves (perineural invasion) or enter blood vessels and lymphatic channels (lymphovascular invasion). These features help explain why the tumour can spread locally and to other parts of the body.

Several microscopic patterns can be seen, including intestinal-type, mucin-producing, signet-ring cell, clear cell, and micropapillary patterns. Rarely, the tumour may show squamous, adenosquamous, or undifferentiated features.

Pathologists also look for a precancerous change called biliary intraepithelial neoplasia. This change involves abnormal cells confined to the surface lining of the bile duct that have not invaded deeper tissues but have the potential to develop into cholangiocarcinoma over time. Finding biliary intraepithelial neoplasia near a tumour supports the idea that the cancer developed gradually from long-standing changes in the bile duct lining.

Cytology (brushings and biopsies)

Because bile ducts are difficult to biopsy surgically, diagnosis is often made using brush cytology obtained during ERCP. In this test, cells are scraped from the bile duct and examined under the microscope.

Findings that suggest cancer include abnormal nuclear shape, enlarged nuclei, overlapping cells, prominent nucleoli, and disorganized clusters. In people with conditions such as primary sclerosing cholangitis, inflammation can make diagnosis more challenging.

Additional tests, such as immunohistochemistry or molecular studies, may improve diagnostic accuracy in complex cases.

Are molecular tests performed?

Molecular testing is not required to diagnose cholangiocarcinoma. However, genetic changes are common in tumour cells and may be identified through testing. These changes do not currently guide routine diagnosis but may influence treatment decisions in selected cases.

What does tumour grade mean?

Pathologists use the term grade to describe how closely the cancer cells resemble normal bile duct cells under the microscope. For cholangiocarcinoma, grade is based on how much of the tumour forms round, gland-like structures, which is a feature of more organized and less aggressive growth.

Tumour grade is important because it helps predict how the cancer is likely to behave. Less organized tumours tend to grow faster and are more likely to spread.

• Well-differentiated cholangiocarcinoma
  More than 95% of the tumour is made up of well-formed glands. These tumours tend to grow more slowly and are generally less aggressive.

• Moderately differentiated cholangiocarcinoma
  Between 50% and 95% of the tumour forms glands. This is the most common grade and falls between well- and poorly differentiated tumours.

• Poorly differentiated cholangiocarcinoma
  Less than 50% of the tumour forms glands. These tumours are more disorganized, behave more aggressively, and are more likely to spread to other parts of the body.

What does perineural invasion mean?

Perineural invasion means that cancer cells are found growing around or along nerves. Nerves can act as pathways that allow tumour cells to spread into nearby tissues.

Perineural invasion is common in extrahepatic cholangiocarcinoma and is an important finding in the pathology report. Its presence is associated with a higher risk of local tumour spread and recurrence, and it can be linked to a worse overall prognosis.

What does lymphovascular invasion mean?

Lymphovascular invasion means that cancer cells are found inside small blood vessels or lymphatic channels. These vessels are part of the body’s circulation system and can provide a route for cancer cells to spread to lymph nodes or distant organs.

When lymphovascular invasion is present, it suggests a higher likelihood of tumour spread and is considered an adverse prognostic feature. For this reason, pathologists carefully examine the tissue for lymphovascular invasion and report whether it is present or absent.

What are margins, and why are they important?

Margins describe the edges of the tissue removed during surgery. After the tumour is removed, a pathologist examines the margins to see if any cancer cells are present at the cut edges.

• A negative margin means no cancer cells are seen at the edge of the specimen, suggesting that the tumour was removed entirely.

• A positive margin means cancer cells are present at the edge, indicating that some tumour may remain in the body.

Margin status is one of the most critical factors in cholangiocarcinoma because complete surgical removal offers the best chance for long-term survival. Positive margins are associated with a higher risk of recurrence and may influence decisions about additional treatment, such as chemotherapy or radiation therapy.

How is cholangiocarcinoma staged?

Extrahepatic cholangiocarcinoma is staged using the TNM system, which considers:

• Tumour size and local extent,

• Spread to nearby lymph nodes, and

• Distant metastases.

The staging system differs slightly depending on whether the tumour is perihilar or distal.

What is the prognosis for a person with cholangiocarcinoma?

Prognosis depends mainly on the stage at diagnosis and whether the tumour can be removed entirely by surgery.

When the tumour is resectable, the 5-year survival rate is approximately 20–30%. If the tumour cannot be surgically removed, outcomes are much poorer.

Certain microscopic features, such as poor differentiation, perineural invasion, and lymphovascular invasion, are associated with a worse prognosis. Tumours with a papillary growth pattern tend to have a better outcome.

Questions to ask your doctor

• Where exactly is my tumour located in the bile duct?
• Can the tumour be surgically removed?
• What did the pathology report show about invasion or margins?
• Has the cancer spread to lymph nodes or other organs?
• What treatment options are recommended for my stage of disease?
• What follow-up testing will I need?