Neuroendocrine Tumor of the Pancreas: Stages and Grades

Approved by the Cancer.Net Editorial Board, 02/2021

ON THIS PAGE: You will learn about how doctors describe a tumor’s growth or spread. This is called the stage. In addition, you can read about how doctors describe how fast the tumor cells are growing and dividing, called the grade. Use the menu to see other pages.

Staging is a way of describing where the tumor is located, if or where it has spread, and whether it is affecting other parts of the body.

Doctors use diagnostic tests and, sometimes, information obtained from surgery, to find out the tumor's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor recommend what kind of treatment is best, and it can help predict a patient's prognosis, which is the chance of recovery. For example, people with a smaller tumor may not need surgery, while many people with a larger tumor do. This is because a pancreas NET that is smaller than 2 centimeters (cm) has a lower risk of spreading. There are different stage descriptions for different types of cancer.

TNM staging system

One tool that doctors use to describe the stage is the TNM system. TNM staging is usually determined after the tumor is removed by surgery and evaluated by a pathologist. Doctors use the results from diagnostic tests and scans to answers these questions:

  • Tumor (T): How large is the primary tumor? Where is it located?

  • Node (N): Has the tumor spread to the lymph nodes? If so, where and how many?

  • Metastasis (M): Has the cancer spread to other parts of the body? If so, where and how much?

The results are combined to determine the stage of cancer for each person.

For a pancreas NET, there are 4 stages: I through IV (1 through 4). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

Here are more details on each part of the TNM system for a pancreas NET.

Tumor (T)

Using the TNM system, the "T" plus a letter or number (1 to 4) is used to describe the size and location of the tumor. If the T is followed by a number in parentheses or the letter “m,” it indicates the number of tumors found or that multiple tumors are found. For example, a T2(3) would mean that the largest tumor found is T2 size and that there are 3 tumors. Tumor size is measured in centimeters (cm). A centimeter is roughly equal to the width of a standard pen or pencil.

Stages may also be divided into smaller groups that help describe the tumor in even more detail. Specific tumor stage information is listed below.

TX: The tumor cannot be evaluated.

The tumor is limited to the pancreas and is less than 2 cm in size.

T2: The tumor is limited to the pancreas and is 2 cm to 4 cm in size.

T3: The tumor is limited to the pancreas and is larger than 4 cm in size, or the tumor is invading the duodenum or bile duct.

T4: The tumor has grown into the stomach, spleen, colon, or adrenal gland, or the wall of the celiac axis or the superior mesenteric artery, which are large vessels.

Node (N)

The "N" in the TNM system stands for lymph nodes. These small, bean-shaped organs help fight infection. Lymph nodes near where the cancer started are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes.

NX: Regional lymph nodes cannot be evaluated.

N0 (N plus zero): The cancer has not spread to the regional lymph nodes.

N1: The cancer has spread to the regional lymph nodes.

Metastasis (M)

The "M" in the TNM system describes whether the cancer has spread to other parts of the body, called metastasis.

M0 (M plus zero): There is no distant spread.

M1: There is distant metastasis.

  • M1a: The cancer has spread only to the liver.

  • M1b: The cancer has spread to at least 1 area beyond the liver, such as a lung, ovary, a nonregional lymph node, the peritoneum, or a bone.

  • M1c: The cancer has spread to both nearby and distant parts of the body.

Cancer stage grouping

Doctors combine the T, N, and M information to decide what stage the cancer is.

Stage I: There is a small tumor in the pancreas and it has not spread elsewhere in the body (T1, N0, M0).

Stage II: The tumor is larger and has not spread to the regional lymph nodes or elsewhere in the body (T2 or T3, N0, M0).

Stage III: The tumor is any size and has spread to the regional lymph nodes (any T, N1, M0). Or, the tumor has spread to the stomach, spleen, colon, or adrenal gland, or the wall of the celiac axis or the superior mesenteric artery, but the cancer has not spread to the regional lymph nodes or anywhere else (T4, N0, M0).

Stage IV: There is distant metastasis (any T, any N, M1).

Grade (G) and degree of differentiation

Doctors also describe a pancreas NET by its grade (G) and degree of differentiation, both features that are determined when the tumor cells are viewed under the microscope.

For NETs, the grade describes how fast the tumor cells are growing and dividing, measured in 2 ways: mitosis and Ki-67. To measure mitosis, the doctor counts the number of dividing cells seen in 2 millimeters squared under a microscope; this is called the mitotic index. Ki-67 is a protein in cells that increases as they prepare to divide. If there is a high percentage of cells in an area with Ki-67, it means that the cells are dividing rapidly. The Ki-67 index is an indicator of how quickly the tumor cells are multiplying and has a range of 1 to 100. For both mitotic index and Ki-67 index, a low value means that the cells are slowly dividing and indicates that the NET is less aggressive. A higher value means that the cells are rapidly dividing and the NET is more aggressive. This grading system is from the World Health Organization (WHO).

The tumor’s grade may help the doctor predict how quickly the cancer will grow and spread. In general, the lower the tumor’s grade, the better the prognosis.

GX: Grade cannot be evaluated.

G1: Mitotic index is less than 2, or Ki-67 index is less than 3.

G2: Mitotic index is between 2 and 20, or Ki-67 index is 3 to 20.

G3: Mitotic index is more than 20, or Ki-67 index is more than 20.

Grade 1 and grade 2 NETs tend to grow slowly. Grade 3 NETs tend to grow fast and are more aggressive. The final grade is based on whichever index (mitotic index or Ki-67) places the tumor in the highest grade category.

Degree of differentiation is also determined by looking at cells under a microscope. Differentiation refers to how much a cancer cell looks like a healthy cell. Well-differentiated tumors look more like healthy cells and grow more slowly. Poorly differentiated cells look less like healthy cells and grow more quickly. Poorly differentiated tumors are usually referred to as neuroendocrine carcinomas (NECs) and are divided into large-cell and small-cell types.

In the latest version of the WHO guidelines, both grade and degree of differentiation are used to place NETs into categories. There is a new category of well-differentiated, grade 3 pancreatic NET, which shows that sometimes a cancer cell can look more like a healthy cell but still multiply quickly.

Recurrent NETs

Recurrent cancer is cancer that has come back after treatment. If the NET does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.

TNM system information used with permission of the American College of Surgeons, Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017), published by Springer International Publishing.

Information about the tumor’s stage and grade will help the doctor recommend a specific treatment plan. The next section in this guide is Types of Treatment. Use the menu to choose a different section to read in this guide.