Hepatocellular carcinoma (HCC)

by Ipshita Kak MD FRCPC
May 17, 2022

What is hepatocellular carcinoma?

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

What are the symptoms of hepatocellular carcinoma?

HCC may produce little or no symptoms at all and as a result, 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 the diagnosis of hepatocellular carcinoma?

The first diagnosis of HCC 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.

How do pathologists grade hepatocellular carcinoma?

Pathologists use the term differentiated to divide HCC into four grades – well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. The grade is based on how much the tumour cells look like normal hepatocytes. A well-differentiated tumour (grade 1) is made up of tumour cells that look almost the same as normal hepatocytes. Additional tests may be required to prove that the cells are cancerous. A moderately differentiated tumour (grade 2) is made up of tumour cells that look similar to normal hepatocytes but are growing in a pattern that is abnormal. A poorly differentiated tumour (grade 3) is made up of tumour cells that look very little like normal hepatocytes. An undifferentiated tumour (grade 4) is made up of tumour cells that look nothing like normal hepatocytes. These cells can look so abnormal that your pathologist may need to order an additional test such as immunohistochemistry to confirm the diagnosis. The grade is important because less differentiated tumours (poorly differentiated and undifferentiated tumours) behave in a more aggressive manner and are more likely to spread to other parts of the body.

What does tumour extension mean?​

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

Tumour extension is important because it 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.

What does vascular invasion mean?

Blood moves around the body through long thin tubes called blood vessels. Pathologists use the term vascular invasion to describe tumour cells that are found inside a blood vessel. Vascular invasion is often divided into venous invasion and small vessel invasion. Venous invasion means that tumour cells were seen in a type of larger blood vessel that brings blood back to the heart. Small vessel invasion means that tumour cells were seen inside a vessel smaller than a vein. These smaller vessels include capillaries, arterioles, and venules. Vascular invasion is important because it is associated with a worse prognosis compared to tumours that do not show vascular invasion.

What is a margin?

​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.

What does treatment effect mean?

​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).

What are lymph nodes?

Lymph nodes are small immune organs located throughout the body. Tumour 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 tumour cells from the tumour to a lymph node is called metastasis.

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

Finding tumour cells in a lymph node is associated with an increased risk that 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).

How do pathologists determine the pathologic stage (pTNM) for hepatocellular carcinoma?

​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 tumour cells in any blood vessels (vascular invasion).
• T2 – There is only one tumour in the liver and it measures more than 2 cm and tumour 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 tumour 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 tumour cells in a lymph node and the number of lymph nodes with tumour 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 tumour 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.