Ductal adenocarcinoma of the pancreas

What is ductal adenocarcinoma of the pancreas?

Ductal adenocarcinoma is the most common type of pancreatic cancer. Ductal adenocarcinoma starts in the pancreas from specialized cells on the inside small channels called ducts. Ductal adenocarcinoma can start anywhere along the length of the pancreas but it commonly involves the part of the pancreas that is closest to the small bowel (also called the ‘head’). Unfortunately, ductal adenocarcinoma can be challenging to diagnose early because it produces vague symptoms. In addition, it is a highly aggressive cancer that can spread quickly to surrounding organs and the liver.

The pancreas

The pancreas is a long, thin organ that sits in the abdomen just below the stomach. The pancreas makes enzymes that help the body break down food in the stomach. The pancreas also makes hormones that allow the body to use sugar (insulin being the most important).

The enzymes produced in the pancreas are made in small structures called glands before being transported out of the pancreas in channels called ducts. The ducts are lined by specialized cells called epithelial cells that form a barrier called the epithelium.

Pancreatic intraepithelial neoplasia (PanIN)

Ductal adenocarcinoma often starts from a pre-cancerous disease called pancreatic intraepithelial neoplasia (PanIN). When examined under the microscope, the abnormal cells in PanIN look similar to the cancer cells in ductal adenocarcinoma. The most important difference is that the abnormal cells in PanIN are only seen inside the duct. There are no abnormal cells in the tissue surrounding the duct. Once the abnormal cells break out of the duct and enter the surrounding tissue, the diagnosis becomes ductal adenocarcinoma. The movement of abnormal cells into the surrounding tissue is called invasion.

How do pathologists make this diagnosis?

The first diagnosis of ductal adenocarcinoma is usually made after a procedure is performed to remove a small sample of tissue. Depending on the amount of tissue removed, the procedure may be called a fine needle aspiration (FNA) biopsy or a core needle biopsy.  Surgery is then performed to remove the entire tumour. Often the tumour is removed with part of the pancreas and small bowel, and stomach in a procedure called a “Whipple”.

Histologic grade

Grade is a word pathologists use to describe the difference between the cancer cells and the normal, healthy epithelial cells in the pancreas. Because the normal epithelial cells in the pancreas connect together to form glands, adenocarcinoma is usually divided into three grades based on how much of the tumour is made of glands:

1. Well differentiated – More than 95% of the tumour is made up of glands.
2. Moderately differentiated – 50 to 95% of the tumour is made up of glands.
3. Poorly differentiated – Less than 50% of the tumour is made up of glands.

Poorly differentiated tumours are associated with a worse prognosis compared to well differentiated tumours.

What to look for in your report after the tumour is removed

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. The tumour size is important because it is used to determine the tumour stage (see Pathologic stage below). Larger tumours are associated with a worse overall prognosis.

Tumour extension​

The pancreas sits very close to other organs and tissues such as the liver, small bowel, stomach, and blood vessels. Cancer cells that travel outside the pancreas and enter any of these organs are described as tumour extension. All organs or tissues that show evidence of tumour extension will be listed in your report. Tumour extension is used to determine the tumour stage (see Pathologic stage below). Tumours that grow into surrounding organs or tissues are associated with a worse prognosis.

Perineural invasion​

Nerves are like long wires made up of groups of cells called neurons. Nerves send information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion means that cancer cells were seen attached to a nerve.

Cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. This increases the risk that the tumour will come back in the same area of the body (recurrence) after treatment.

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.

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.

Margins

​A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The number of margins described in your report will depend on the type of surgery that was performed. Most reports describe margins in the pancreas and in any surrounding organs that were removed at the same time as the tumour.

The two most important margins in the pancreas are:

• The common bile duct margin – The common bile duct is a channel that connects the liver to the pancreas.
• The pancreatic margin – This is the part of the pancreas that was cut in order to remove the tumour. The amount of pancreas removed will depend on the location of the tumour in the pancreas.

Other margins that may be described in your report include:

• The uncinate process – This is the part of the pancreas which rests against the back of the abdomen. The tissue around this part of the pancreas needs to be cut in order to remove the pancreas from the body.
• The duodenal (or small bowel) margin – Part of the small bowel is commonly removed at the same time as the tumour in the pancreas. The small bowel margin is a place where the surgeon cut the small bowel to remove the tumour.
• The gastric (or stomach) margin – Part of the stomach is commonly removed at the same time as the tumour in the pancreas. The gastric margin is the place where the surgeon cut the stomach to remove the tumour.

All of these margins will be very closely examined under the microscope by your pathologist to determine the margin status.  A margin is considered negative when there are no cancer cells at the edge of the cut tissue. A margin is considered positive when there are cancer cells within 1 millimetre of the edge of the cut tissue. Pancreatic intraepithelial neoplasia (PanIN) at the margin may also be reported as positive. Cancer cells at the cut edge of the tissue (a positive margin) are associated with a higher risk that the tumour will re-grow in the same site after treatment.

Treatment effect

​If you received treatment (either chemotherapy or 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).

There are several different systems used to describe treatment effects. In the most common system, the treatment effect is described on a scale of 0 to 3 with 0 being no residual viable tumour (all the cancer cells are dead) and 3 being no response to therapy (all or most of the cancer cells are alive). Lymph nodes with cancer cells will also be examined for treatment effect (see Lymph nodes below).

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.

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 ductal adenocarcinoma 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 ductal adenocarcinoma

Ductal adenocarcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and the invasion of nearby organs.

• Tis – Abnormal cells are only seen inside the duct. No invasive tumour is seen.
• T1 – The size of the tumour is 2 cm or less.
• T2 – The size of the tumour is greater than 2 cm but no more than 4 cm.
• T3 – The size of the tumour is greater than 4 cm.
• T4 – The tumour has travelled outside of the pancreas and entered one of the large nearby blood vessels (see Tumour extension above).

Nodal stage (pN) for ductal adenocarcinoma

Ductal adenocarcinoma 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.

• N0 – No cancer cells were seen in any of the lymph nodes examined.
• N1 – Cancer cells were seen in at least one lymph node but not more than 3 lymph nodes.
• N2 – Cancer cells were seen in more than 3 lymph nodes.
• NX – No lymph nodes were sent for pathologic examination.

Metastatic stage (pM) for ductal adenocarcinoma

Ductal adenocarcinoma is given 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 sent 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 2, 2021)