Jason Wasserman MD PhD FRCPC
January 28, 2025
Ductal adenocarcinoma, also called ductal carcinoma, is the most common type of pancreatic cancer. It starts in the pancreas from specialized cells lining small channels called ducts. These ducts help transport digestive enzymes produced by the pancreas. Ductal adenocarcinoma can develop in any part of the pancreas but is most often found in the part closest to the small intestine, known as the “head” of the pancreas. This aggressive type of cancer can spread quickly to nearby organs and the liver.
Symptoms of ductal adenocarcinoma are often non-specific, meaning many conditions can cause them. Most people do not experience noticeable symptoms until the tumour has spread outside the pancreas. Possible symptoms include:
There is no single known cause of ductal adenocarcinoma, but several factors increase the risk of developing this cancer. Smoking is the most important risk factor, which can increase the risk by two to three times.
Other risk factors include:
The diagnosis of ductal adenocarcinoma usually starts with a biopsy, where a small tissue sample is removed for testing. This may involve a fine needle aspiration biopsy (FNAB) or a core needle biopsy. If the biopsy confirms the diagnosis, surgery is often performed to remove the tumour. This surgery typically involves removing part of the pancreas along with nearby structures like the small bowel and stomach in a procedure called a “Whipple operation.”
Grade is a term used to describe how different the tumour cells in ductal adenocarcinoma look and behave compared to normal cells in the pancreas. The pathologist evaluates several features to assign a grade, including:
When a tumour shows variation in these features (called intratumoral heterogeneity), the highest grade is assigned, even if only a small part of the tumour appears more aggressive. For example, if most of the tumour is well differentiated but a small area is poorly differentiated, the overall grade will be based on the poorly differentiated area.
Using the above criteria, pathologists group ductal adenocarcinoma of the pancreas into one of the three following grades:
Doctors use the grade to help predict how the tumour will behave and to guide treatment decisions. Studies show that higher-grade tumours are associated with worse survival outcomes, making the grade an independent factor in understanding a person’s prognosis.
Mismatch repair proteins (MMR) are a system inside normal, healthy cells that fix mistakes in our genetic material (DNA). The system comprises different proteins, the four most common being MSH2, MSH6, MLH1, and PMS2. The four MMR proteins work in pairs to fix damaged DNA. Specifically, MSH2 works with MSH6, and MLH1 works with PMS2. If one protein is lost, the pair cannot function normally, and the risk of developing cancer increases.
The most common way to test for mismatch repair proteins is immunohistochemistry. This test allows pathologists to see if the tumour cells produce all four mismatch repair proteins. The results of this test are typically reported as follows:
Mismatch repair testing is important because it can help predict how well specific treatments may work. For instance, cancers with a loss of mismatch repair protein expression are more likely to respond to immunotherapy treatments like PD-1 or PD-L1 inhibitors. This is because the many mutations often found in deficient tumours can produce new antigens that make the tumour more visible and vulnerable to the immune system.
Mismatch repair testing is also performed to identify patients who may have Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). Lynch syndrome is a genetic disorder that increases the risk of developing various types of cancer, including esophageal cancer, colon cancer, endometrial cancer, ovarian cancer, and stomach cancer.
When pathologists examine ductal adenocarcinoma of the pancreas under the microscope, they see cancer cells forming gland-like structures that look similar to the normal ducts in the pancreas. However, these cancerous glands grow in a disorganized way, spreading into the surrounding pancreas and causing a reaction in the nearby tissue. This reaction, called desmoplasia, appears as dense, fibrous tissue around the cancerous glands and is a hallmark of this type of cancer.
In well differentiated tumours, the cancer cells form glands that closely resemble normal pancreatic ducts. These glands may look fairly regular but often have features that suggest cancer, such as:
In moderately differentiated tumours, the cancer cells still form glands, but these are more abnormal. Pathologists may see a mix of different gland shapes and patterns, such as cribriform (gland openings that resemble a sieve) or papillary (finger-like projections). At the edges of the tumour, the glands may become smaller and more irregular, and some cancer cells may appear individually.
Poorly differentiated tumours look very different from normal pancreas tissue. These tumours often consist of solid sheets of cancer cells without any recognizable gland structure. The cells may be pleomorphic (vary in size and shape) and may not produce much mucin. Areas of dead tissue (necrosis) and bleeding are common. These tumours tend to grow and spread more aggressively.
The tumour will be measured after it is removed. The size is important because it helps determine the tumour stage (pT). Larger tumours are often associated with a worse prognosis.
The pancreas is located near many vital organs and tissues, including the liver, stomach, small intestine, and large blood vessels. Tumour extension refers to cancer cells spreading beyond the pancreas into these nearby structures. This information is included in your pathology report because it affects the tumour stage (pT) and is linked to the prognosis.
Ductal adenocarcinoma often begins as a pre-cancerous condition called pancreatic intraepithelial neoplasia (PanIN). In PanIN, abnormal cells are found inside the ducts but do not invade surrounding tissues. When these abnormal cells move into the surrounding tissue, the condition becomes ductal adenocarcinoma. This process is called invasion.
Perineural invasion occurs when cancer cells are found inside or around nerves. Nerves transmit signals, such as pain or temperature, between the body and the brain. Cancer cells can use nerves to spread to surrounding tissues, increasing the risk of tumour recurrence after surgery.
Lymphovascular invasion means cancer cells are found inside blood vessels or lymphatic vessels. Blood vessels carry blood throughout the body, while lymphatic vessels carry a fluid called lymph to small immune organs called lymph nodes. Cancer cells can use these vessels to spread to other body parts, such as lymph nodes or distant organs.
Margins refer to the edges of tissue removed during surgery. A negative margin means no cancer cells are found at the edge, while a positive margin means cancer cells are at the cut edge. Positive margins suggest that some cancer may have been left behind, and additional treatment, such as surgery or radiation therapy, may be needed.
Key margins in the pancreas include:
If you had chemotherapy or radiation therapy before surgery, your pathology report will describe how much of the tumour is still alive. This is called the treatment effect and is usually graded on a scale of 0 to 3, with 0 meaning no remaining cancer cells and 3 meaning little or no response to treatment.
Lymph nodes are small immune organs that cancer cells can spread to through lymphatic vessels. During surgery, nearby lymph nodes are often removed and examined. Your report will describe the total number of lymph nodes examined and how many contained cancer cells.
The number of lymph nodes with cancer is important for determining the nodal stage (pN) and prognosis.
The pathologic stage for ductal adenocarcinoma of the pancreas is determined using the TNM system, which stands for Tumour (T), Nodes (N), and Metastases (M). Each category is assigned a number:
Tumour stage (pT):
Nodal stage (pN):
The prognosis for ductal adenocarcinoma of the pancreas is generally poor, making it one of the most challenging cancers to treat. Without treatment, the average survival time is only 3 to 5 months. Even with surgery, which is the most effective treatment, the average survival time increases to 10 to 20 months. Unfortunately, only 10 to 20% of patients are eligible for surgery at the time of diagnosis because most tumours are discovered too late.
The overall 5-year survival rate for all patients with ductal adenocarcinoma is about 8%. This improves slightly to 15–25% for those who undergo successful surgery. However, even after surgery, 70–90% of tumours return (recur) within two years, often in the pancreas, liver, peritoneal cavity, or nearby lymph nodes.
While chemotherapy and radiation therapy may help prolong survival, the improvement is often modest. These treatments are typically used before surgery (neoadjuvant therapy) to shrink the tumour or after surgery (adjuvant therapy) to reduce the risk of recurrence.