Neuroendocrine Tumor of the Gastrointestinal Tract: Stages and Grades

Approved by the Cancer.Net Editorial Board, 07/2022

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.

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What is staging?

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

Doctors use diagnostic tests to find out the cancer's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor recommend the best kind of treatment, and it can help predict a patient's prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer.

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TNM staging system

One tool that doctors use to describe the stage is the TNM system. Doctors use the results from diagnostic tests and scans to answer 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 GI tract 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. Staging for a GI tract NET is based on the location of the primary tumor. The TNM system described below covers GI tract NETs found in these locations:

  • Stomach

  • Duodenum and ampulla of Vater (parts of the small intestine)

  • Jejunum and ileum (parts of the small intestine)

  • Appendix

  • Colon and rectum

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Tumor (T) – by organ

Using the TNM system, the "T" plus a letter or number (0 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).

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

Stomach

TX: The tumor cannot be evaluated.

T0 (T zero): There is no evidence of a tumor.

T1: The tumor is 1 cm or smaller and has grown into a deeper layer of cells in the stomach, the lamina propria or submucosa.

T2: The tumor is larger than 1 cm in size, or it has grown into the muscle layer of the stomach, called the muscularis propria.

T3: The tumor has grown through the muscularis propria and into the subserosa layer behind it.

T4: The tumor has grown into the layer of tissue on the outside of the stomach, called the serosa or peritoneum, or it has spread into nearby organs or structures.

Duodenum and ampulla of Vater (small intestine)

The duodenum is the first part of the small intestine after the stomach. The ampulla of Vater is a small bump in the duodenum where liquids from the bile ducts and pancreas enter the small intestine.

TX: The tumor cannot be evaluated.

T1: The tumor is 1 cm or smaller and only involves the top layer of mucus membrane or connective tissue on top of the muscle layer of the duodenum or it only involves the sphincter of Oddi. The sphincter of Oddi is a muscle that controls the flow of digestive fluids into the duodenum through the ampulla of Vater.

T2: The tumor is larger than 1 cm in size. Or it has grown into the muscle layer of the duodenum, called the muscularis propria, or through the sphincter of Oddi and into the duodenum.

T3: The tumor has grown into the pancreas or the tissue surrounding the pancreas.

T4: The tumor has grown into the peritoneum or other organs.

Jejunum and ileum (small intestine)

The jejunum and ileum are the parts of the small intestine that connect the duodenum to the large intestine.

TX: The tumor cannot be evaluated.

T0 (T zero): There is no evidence of a tumor.

T1: The tumor is 1 cm or smaller and only involves the top layers of tissue in the small intestine.

T2: The tumor is larger than 1 cm in size, or it has grown into the muscle layer of the small intestine.

T3: The tumor has grown through the muscle layer and into the tissues beyond, but it has not grown outside of the small intestine.

T4: The tumor has grown past the outside of the small intestine and into the peritoneum or other organs.

Appendix

TX: The tumor cannot be evaluated.

T0 (T zero): There is no evidence of a tumor.

T1: The tumor is 2 cm or smaller.

T2: The tumor is more than 2 cm but less than or equal to 4 cm in size.

T3: The tumor is larger than 4 cm, or it has grown into the layers of tissue on the outside of the appendix.

T4: The tumor has grown through the peritoneum or has invaded nearby organs or structures.

Colon and rectum

TX: The tumor cannot be evaluated.

T0 (T zero): There is no evidence of a tumor.

T1: The tumor is 2 cm or smaller and has grown past the top layer of cells and into the layers beneath, such as the lamina propria or submucosa.

  • T1a: The tumor is less than 1 cm in size.

  • T1b: The tumor is between 1 cm and 2 cm in size.

T2: The tumor has grown into the muscle (muscularis propria). Or it is more than 2 cm in size and has invaded the lamina propria or submucosa.

T3: The tumor has spread through the muscle and into the subserosal tissue behind it.

T4: The tumor has spread to the peritoneum or has invaded nearby organs or structures.

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Node (N) — for all parts of the GI tract

The “N” in the TNM staging 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: The lymph nodes cannot be evaluated.

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

N1: The cancer has spread to the regional lymph nodes. Jejunum and ileum only: The cancer has spread to fewer than 12 lymph nodes.

N2 (jejunum and ileum only): The cancer has spread to 12 or more lymph nodes and/or the masses are larger than 2 cm.

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Metastasis (M) — for all parts of the GI tract

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

M0 (M 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, lymph node, the peritoneum, or bone.

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

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Stage groups for GI tract NETs

Doctors combine the T, N, and M information (see above) to say what stage the cancer is.

Stomach

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

Stage II: The tumor is larger and has grown as far as the subserosa, which is behind the layer of muscle in the stomach. The cancer has not spread to the lymph nodes or elsewhere in the body (T2 or T3, N0, M0).

Stage III: The tumor is any size, and the cancer has spread to regional lymph nodes (any T, N1, M0). Or, the tumor has spread to the outside of the stomach, but the cancer has not spread to the lymph nodes or elsewhere (T4, N0, M0).

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

Duodenum and ampulla of Vater (small intestine)

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

Stage II: The tumor is larger than 1 cm, or it has grown as far as the pancreas. The cancer has not spread to the lymph nodes or elsewhere in the body (T2 or T3, N0, M0).

Stage III: The tumor is any size, and the cancer has spread to regional lymph nodes (any T, N1, M0). Or, the tumor has spread to the peritoneum or other organs, but the cancer has not spread to the lymph nodes or elsewhere (T4, N0, M0).

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

Jejunum and ileum (small intestine)

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

Stage II: The tumor is larger than 1 cm and has grown as far as the subserosa, which is behind the layer of muscle in the small intestine. The cancer has not spread to the lymph nodes or elsewhere in the body (T2 or T3, N0, M0).

Stage III: The tumor is any size, and the cancer has spread to regional lymph nodes (any T, N1 or N2, M0). Or, the tumor has spread to the peritoneum or to other organs or structures, but the cancer has not spread to the lymph nodes or elsewhere (T4, N0, M0).

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

Appendix

Stage I: There is a tumor of 2 cm or less, and it has not spread elsewhere (T1, N0, M0).

Stage II: The tumor is larger than 2 cm and has grown as far as the membrane that connects the appendix to the abdomen wall. The cancer has not spread to the lymph nodes or elsewhere in the body (T2 or T3, N0, M0).

Stage III: The tumor is any size, and the cancer has spread to regional lymph nodes (any T, N1, M0). Or, the tumor has spread to the peritoneum or beyond, but the cancer has not spread to the lymph nodes or elsewhere (T4, N0, M0).

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

Colon and rectum

Stage I: There is a tumor of 2 cm or less, and it has not spread elsewhere (T1, N0, M0).

Stage IIA: The tumor has grown into the muscle. Or it is more than 2 cm in size and has invaded the lamina propria or submucosa. The cancer has not spread (T2, N0, M0).

Stage IIB: The tumor has spread through the muscle and into the subserosal tissue behind it. The cancer has not spread to the lymph nodes or elsewhere in the body (T3, N0, M0).

Stage IIIA: The tumor has spread to the peritoneum or has invaded nearby organs or structures, but the cancer has not spread to the lymph nodes or elsewhere (T4, N0, M0).

Stage IIIB: The tumor is any size, and the cancer has spread to regional lymph nodes (any T, N1, M0).

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

Recurrent: Recurrent cancer is cancer that has come back after treatment. If the cancer 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.

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.

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Grade (G)

Doctors may also describe a GI tract NET by its grade (G), with a number from 1 to 3. For NETs, the grade describes how fast the tumor cells are growing and dividing, a process called mitosis.

To measure mitosis, the doctor counts the number of dividing cells seen in 10 high-power fields under a microscope. This is called the mitotic count. The doctor can also measure the Ki-67 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.

The cancer’s grade may help the doctor predict how quickly the NET will grow and spread. In general, the lower the tumor’s grade, the better the prognosis. The grade scale below applies to all types of GI tract NETs.

GX: Grade cannot be evaluated.

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

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

G3: Mitotic count 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 count or Ki-67) places the tumor in the highest grade category.

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Degree of differentiation

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. Well-differentiated tumors can be grade 1, 2, or 3; the well-differentiated grade 3 category is newly recognized in the World Health Organization pathology system. (Please note this link takes you to a separate website.)

Poorly differentiated cells look less like healthy cells and grow more quickly. Poorly differentiated tumors are always grade 3 and are usually referred to as neuroendocrine carcinomas (NECs) and are divided into large-cell and small-cell types.

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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.