by Ipshita Kak MD FRCPC
March 9, 2023
Ductal adenocarcinoma (also called ductal carcinoma) is the most common type of pancreatic cancer. It starts in the pancreas from specialized cells on the inside of 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’). Ductal adenocarcinoma is a highly aggressive cancer that can spread quickly to surrounding organs and the liver.
The symptoms of ductal adenocarcinoma of the pancreas are non-specific and most people do not experience any symptoms until that tumour has spread outside of the pancreas. Possible symptoms include loss of appetite, nausea, indigestion, back pain, fatigue, and unexplained weight loss. Jaundice (the yellowing of the skin and eyes) is often a late sign.
No single cause for ductal adenocarcinoma of the pancreas has been identified. However, the most important risk factor is smoking which increases a person’s risk by 2 to 3 times compared to non-smokers. Other risk factors include obesity, lack of physical activity, high intake of saturated fats, and low intake of vegetables and fruits.
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 biopsy FNAB) 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”.
Pathologists use the term differentiated to divide ductal adenocarcinoma of the pancreas into three levels or grades: well differentiated, moderately differentiated, and poorly differentiated. In order to determine the level of differentiation, pathologists look at the percentage of tumour cells that are forming round structures called glands. The level of differentiation is important because poorly differentiated tumours are more aggressive and are more likely to spread outside of the pancreas and into other organs.
After the tumour is removed fully it will be measured and the size will be included in your report. The tumour size is important because it is used to determine the pathologic tumour stage (pT). Larger tumours are associated with a worse overall prognosis.
The pancreas sits very close to other organs and tissues such as the liver, small bowel, stomach, and blood vessels. The term tumour extension is used to describe cancer cells that spread outside the pancreas and into any of these organs. All organs or tissues that show evidence of tumour extension will be listed in your report. Tumour extension is important because it is used to determine the pathologic tumour stage (pT) and because tumour extension into surrounding organs or tissues is associated with a worse prognosis.
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.
Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.
Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.
In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.
Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.
The two most important margins in the pancreas are:
Other margins that may be described in your report include:
Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.
A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved. For example, additional treatment may not be necessary for a benign (non-cancerous) type of tumour but may be strongly advised for a malignant (cancerous) type of tumour.
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 effects.
Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as a lymph node is called a metastasis.
Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.
If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.
The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.
What does it mean if a lymph node is described as positive?
Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.
What does it mean if a lymph node is described as negative?
Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.
The pathologic stage for ductal adenocarcinoma of the pancreas 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.
Ductal adenocarcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and tumour extension into nearby organs.
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.
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.