Hepatocellular carcinoma (HCC)

What is hepatocellular carcinoma?

Hepatocellular carcinoma (HCC) is a type of liver cancer. Hepatocellular carcinoma starts from specialized cells called hepatocytes in the liver. Hepatocellular carcinoma is the most common type of liver cancer in adults. People with cirrhosis or long-standing hepatitis B or C infections are at high risk for developing hepatocellular carcinoma.

The liver

The liver is a large organ found in the right upper part of the abdomen, just below the ribs. Most of the liver is made up of special cells called hepatocytes. The liver acts as a factory, producing chemical products such as proteins that our body uses every day. Two of the most important products made by the liver are bile and albumin. Bile is a liquid that the body uses to digest food. Albumin is a protein that helps our blood function normally. The liver also acts like a recycling plant removing waste and toxins from the body.

Symptoms of hepatocellular carcinoma

Hepatocellular carcinoma may produce little or no symptoms at all and as a result, the cancer may not be detected until it is at an advanced stage. This is because the liver is extremely efficient and it is capable of functioning normally even when a large area of the liver is affected by the disease. When symptoms occur, they may include loss of weight and appetite, yellowing of the skin (jaundice), swelling, pain, or lump in the abdomen.

How do pathologists make this diagnosis?

The first diagnosis of hepatocellular carcinoma is usually made by a doctor who takes pictures of your liver using an ultrasound (U/S) or computed tomography scan (CT scan). A small sample of tissue may be removed in a procedure called a biopsy. The tissue will then be sent to a pathologist who will examine it under the microscope.

Histologic grade

Pathologists use the word grade to describe the difference between the cancer cells and the normal, healthy hepatocytes. The grade can only be determined after the tumour has been examined under the microscope by your pathologist.

Hepatocellular carcinoma is usually divided into four levels:​

  1. Well differentiated – The tumour cells in a well differentiated tumour look very similar to normal, healthy hepatocytes. Additional tests may be used to confirm the diagnosis of cancer.
  2. Moderately differentiated – The tumour cells in a moderately differentiated tumour look similar to normal, healthy hepatocytes but are growing in a pattern that is clearly abnormal.
  3. Poorly differentiated – The tumour cells in a poorly differentiated tumour are very abnormal and look very little like normal hepatocytes.
  4. Undifferentiated – The tumour cells in an undifferentiated tumour look nothing like normal hepatocytes. Special tests such as immunohistochemistry may be needed to confirm that the tumour cells are in fact from the liver.

Poorly differentiated and undifferentiated tumours are more likely to spread to other parts of the body or to re-grow after surgery.

Tumour size

This is the size of the tumour measured in centimetres. Your report may only describe the greatest dimension. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in the greatest dimension.

Tumour extension

Tumour extension describes how far the cancer cells have travelled from the main tumour in the liver into adjacent organs such as large vessels, the gallbladder, and the small bowel. All organs or tissues that show evidence of tumour extension will be listed in your report.

In the liver, larger tumours (greater than 5 cm) or multiple tumours are more likely to show vascular invasion than small single tumours.

Tumour extension is used to determine the tumour stage (see Pathologic stage below). Tumours that grow into large blood vessels or other organs are more likely to spread to other parts of the body and are associated with a worse prognosis.

Lymphovascular invasion

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.

lymphovascular invasion

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.


​A margin is any tissue that was cut by the surgeon in order to remove the liver (or part of it) and tumour from your body.


All of these margins will be very closely examined under the microscope by your pathologist to determine the margin status. Margins will only be described in your report after the entire tumour has been removed. Margins will not be described after a biopsy. Tumour at or within 1 millimetre of the margin has a higher chance of re-growing at the same site after surgery.

Treatment effect

​If you received treatment (either localized chemotherapy or local radiation therapy) for your cancer prior to the tumour being removed, your pathologist will examine all of the tissue submitted to see how much of the tumour is still alive (viable).

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Lymph node

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

Finding cancer cells in a lymph node is associated with an increased risk that the cancer will come back at a distant body site such as the lungs in the future. This information is also used to determine the nodal stage (see Pathologic stage below).

Pathologic stage (pTNM)

​The pathologic stage for hepatocellular carcinoma 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 a worse prognosis.

Tumour stage (pT) for hepatocellular carcinoma

Hepatocellular carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and the invasion of adjacent vessels and organs.

  • T1 – There is only one tumour in the liver and it measures less than or equal to 2 cm OR it is greater than 2 cm but there are no cancer cells in any blood vessels (vascular invasion).
  • T2 – There is only one tumour in the liver and it measures more than 2 cm and cancer cells are inside blood vessels (vascular invasion) OR there are multiple tumours in the liver but none are larger than 5 cm.
  • T3 – There is more than one tumour in the liver and at least one of them is larger than 5 cm.
  • T4 – A tumour of any size with cancer cells that have entered a large vein inside the liver OR an organ outside of the liver OR they are on the outer surface of the liver.
Nodal stage (pN) for hepatocellular carcinoma

Hepatocellular carcinoma is given a nodal stage between 0 and 2 based on the presence or absence of cancer cells in a lymph node and the number of lymph nodes with cancer cells.

If no lymph nodes are involved the nodal stage is 0. If no lymph nodes are submitted for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

Metastatic stage (pM) for hepatocellular carcinoma

Hepatocellular carcinoma is assigned a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

by Ipshita Kak MD FRCPC (updated July 11, 2021)
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