Liver and bile ducts-

Intrahepatic cholangiocarcinoma

This article was last reviewed and updated on April 13, 2019
by Stephanie Reid MD FRCPC

Quick facts:

  • Intrahepatic cholangiocarcinoma is a type of cancer which starts from the bile ducts found inside the liver.

  • The bile ducts are tubes which connect the liver and gallbladder with the intestine.

  • Your pathology report for intrahepatic cholangiocarcinoma will include important information such as the number of tumours seen, their size, and whether cancer cells were seen inside any blood vessels.


Normal bile ducts

The bile duct system, often called the biliary tree, is a group of tubes which connect the liver, and gallbladder to the intestine. They allow bile and other materials produced by the liver to travel into the intestine, where they help with digestion or are removed from the body as stool.


The bile duct system is divided into parts based on location of the duct. The ducts that are found inside the liver are called intrahepatic. The intrahepatic ducts are tiny and are located close to the liver cells that make bile. Before exiting the liver, the tiny intrahepatic ducts join to form larger ducts.


Outside of the liver the larger ducts join to form two much larger ducts that drain the left and right side of the liver. These two ducts are called the left hepatic duct and right hepatic duct. As they travel towards the gallbladder, the left and right hepatic ducts join to form the common hepatic duct.


Like the liver, the gallbladder is also drained by a duct called the cystic duct. Shortly after leaving the gallbladder, the cystic duct joins with the common hepatic duct and together they form the common bile duct. The common bile duct then passes through a portion of the pancreas and empties into the small intestine.

What is cholangiocarcioma?

Cholangiocarcinoma is a type of cancer that starts from cells normally found inside the bile ducts. Cholangiocarcinoma is divided into 3 categories based on where the tumour is located within the bile duct system.


  1. Intrahepatic cholangiocarcinoma – These tumours start in a bile duct located inside the liver.

  2. Perihilar cholangiocarcinoma - These tumours start in a bile duct just outside of the liver. Tumours that start where the left and right hepatic ducts join are given the special name Klatskin tumours.

  3. Distal cholangiocarcinoma – These tumours start in a larger bile duct close to the intestine (often in the common bile duct).


Unfortunately, most patients with cholangiocarcinoma experience very few symptoms until the tumour reaches an advanced stage and blocks the drainage of the bile ducts. At this point, patients may experience pain, weight loss, pale coloured stool, itching, pain in the abdomen or back, and yellowing of the skin.


The diagnosis of cholangiocarcinoma is made after a doctor takes a small sample of tissue from the bile ducts and sends it to a pathologist for examination. The sample can be taken by brushing the inside of the duct or by performing a biopsy with a needle. The diagnosis may also only be made after the entire tumour is removed.

Histologic grade

Grade is a word that pathologists use to describe how abnormal the cancer cells look compared to the normal, healthy cells found in the same location of the body. For cholangiocarcinoma, the tumour cells are compared to the normal epithelial cells that line the inside of the bile ducts.


Because the normal cells connect together to form tubes, the grade also depends on the amount of tube-like structures seen in the tumour. Pathologists call these tube-like structures glands and cholangiocarcinoma is divided into three different grades based on the amount of cancer cells that are forming glands.


  • Grade 1 (well differentiated) – More than 95% of the tumour is made up of glands.

  • Grade 2 (moderately differentiated) - 50 to 95% of the tumour is made up of glands.

  • Grade 3 (poorly differentiated) – Less than 50% of the tumour is made up of glands.

Why is this important? Higher grade (grade 2 and 3) tumours grow faster and are more likely to spread to other parts of the body. 

Number of tumours (tumour focality)

One or more tumours may be found inside the liver. If there is only one tumour, it will be described in your report as solitary. If more than one tumour is found, your report will describe the size and location of each tumour.

Why is this important? More than one tumour increases the tumour stage (see Pathologic stage below) and is associated with worse prognosis.

Tumour size

These tumours are measured in three dimensions but usually the largest dimension is the only one included in the report. For example, if a tumour measures 1.5 cm by 0.9 cm by 0.5 cm, the report will describe the tumour size as 1.5 cm in greatest dimension.


Tumour size will only be described in your report after the entire tumour has been removed. It will not be reported in a biopsy specimen.

Tumour growth pattern

When examined under the microscope, intrahepatic cholangiocarcinoma can show several different patterns of growth. Some tumours grow as a round group of cells and the tumour is relatively easy to see during surgery and radiological tests. This pattern of growth is called mass-forming.


In contrast, some tumours are hard to see because they do not form a single large group. Instead, the cancer cells grow along the inside of the bile ducts. This pattern of growth is called periductal or infiltrating.


Finally, some tumours show both a mass-forming and periductal/infiltrating pattern of growth.

Tumour extension

Tumour extension describes how far the cancer cells have traveled through the bile ducts and liver. Tumour extension is also used to describe cancer cells that have moved outside the bile ducts and have entered a nearby organ or tissue (for example, the pancreas or small bowel). The movement of cancer cells outside of the bile ducts and into a nearby organ or tissue is called invasion.


Pathologists describe intrahepatic cholangiocarcinoma tumour extension in the following ways:


  • Tumour confined to the intrahepatic bile ducts - The cancer cells are only seen inside the small bile ducts within the liver.

  • Tumour confined to liver parenchyma - The cancer cells have traveled outside of the bile ducts and into the surrounding normal liver cells.

  • Tumour involving the peritoneal surface - The cancer cells have broken through the thin layer of tissue that surrounds the liver and are seen within the abdominal cavity.

  • Tumour directly invades the gallbladder - The cancer cells have traveled outside of the bile ducts and into the gallbladder.

  • Tumour invades nearby organs (other than the gallbladder) - The cancer cells have traveled outside of the bile ducts and into a nearby organ such as the pancreas, small bowel, or colon.


Why is this important? Tumour extension is important because tumours that have grown outside the bile ducts and into other organs or tissues are more likely to regrow in the same area after treatment or to spread to another part of the body.

Lymphatic and vascular invasion

Lymphatic and blood vessels are found throughout your body. These vessels are used for blood cells, immune cells, and other substances to travel from one location to another.


Cancer cells found inside a lymphatic vessel is called lymphatic invasion while cancer cells found inside a blood vessel is called vascular invasion. 


Why is this important? Tumours with vascular invasion are given a higher tumour stage (pT) than tumours without vascular invasion (see Pathologic stage below). Tumours with vascular invasion are also more likely to spread to other parts of the body including the liver.


When a surgery is performed to remove an intrahepatic cholangiocarcinoma, the surgeon will have to cut through normal tissue in order to remove the tumour from your body. A margin is the cut edge of the tissue that was removed. It represents the line that separates the tissue that was removed from the tissue left in your body.


For intrahepatic cholangiocarcinoma, the surgeon will need to cut out a portion of your liver (because the tumour is inside the liver). The surgeon will also need to cut through parts of the bile duct which are outside of the liver. These two margins will be described in your report as the hepatic parenchymal margin (liver margin) and the bile duct margin.


A margin is considered positive when there are cancer cells near the cut edge of the tissue. The margin will be described as negative if no cancer cells are seen at the cut edge of the tissue.


Why is this important? A positive margin is associated with a higher risk that the tumour will re-grow in the same site again after treatment.

Perineural invasion

Nerves are located throughout all parts of your body. When cancer cells come in contact with nerves and wrap around them it is called perineural invasion. When cancer cells invade nerves, they can then travel along the nerve to areas far from the original location of the tumour.


Why is this important? When perineural invasion is seen, there is a higher risk that the tumour will re-grow at the same site or spread (metastasize) to a distant site away from the liver.

Lymph nodes

Lymph nodes are small organs attached to lymphatic vessels. They contain cells from the immune system which help to defend our body from infections. Cancer cells that enter a lymphatic vessel can travel to a nearby lymph node. This process is called lymph node metastasis. Once cancer cells have entered a lymph node there is a higher risk that cancer cells will travel to other areas throughout your body.


All lymph nodes sent to pathology will be carefully examined to see if any contain cancer cells. Your pathology report will describe the total number of lymph nodes seen and if any contained cancer cells.

Pathologic stage (pTNM)
​The pathologic stage for intrahepatic cholangiocarcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.


This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and worse prognosis.


Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.

Tumour stage (pT) for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma is given a tumour stage of either Tis, 1, 2, 3, or 4. The tumour stage is based on the tumour extension, the number of tumours present, and if vascular invasion is identified (see above sections for more details).


  • Tis – Cancer cells are only seen inside the bile ducts

  • T1 – Only a single tumour is seen and there is no vascular invasion. This stage is divided into T1a for tumours that are less than or equal to 5 cm and T1b stage for tumours that are larger than 5 cm.

  • T2 – One tumour is found with vascular invasion within the liver OR multiple tumours are found with or without vascular invasion.

  • T3 – The cancer cells have broken through the capsule on the liver surface (visceral peritoneum)

  • T4 – Cancer cells are seen in organs or tissues outside of the liver.


Nodal stage (pN) for intrahepatic cholangiocarcinoma

Cholangiocarcinoma is given a nodal stage between 0 and 1. If no cancer cells are seen in any of the lymph nodes examined, the stage is pN0. If cancer cells are found in any lymph nodes, the stage is pN1. If no lymph nodes are sent for pathologic examination, the nodal stage cannot be determined and is listed as pNX.


Metastatic stage (pM) for intrahepatic cholangiocarcinoma


Intrahepatic cholangiocarcinoma is given a metastatic stage of 1 if there are cancer cells at a distant site in the body. The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. If no tissue from a distant site has been sent for pathologic examination, the metastatic stage cannot be determined and is listed as pMX.

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