Pancreatic Neuroendocrine Tumor (pNET) Stages

How is the stage of a pancreatic neuroendocrine tumor (pNET) determined?

The staging system most often used for pNETs is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:

• The size and extent of the main tumor (T): How large is the tumor? Has it grown into nearby structures or organs?
• The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
• The spread (metastasis) to distant sites (M): Has the cancer spread to distant organs? (The most common site of spread is the liver.)

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage. For more information, see Cancer Staging.

The system described below is the most recent version of the AJCC system, effective as of January 2018. It is used to stage well-differentiated pancreatic NETs, but not high-grade pNETs (known as neuroendocrine carcinomas) or other types of pancreatic cancer, which have their own staging system.

Pancreatic NETs are typically given a clinical stage based on the results of a physical exam, biopsy, and imaging tests (as described in Tests for Pancreatic Neuroendocrine Tumor). If surgery is done, the pathologic stage (also called the surgical stage) is determined by examining tissue removed during the operation. 

Staging for pNETs can be complex. If you have any questions about the stage of your cancer or what it means, ask your doctor to explain it to you in a way you understand.

Stages of pancreatic neuroendocrine tumors

AJCC Stage	Stage grouping	Stage description*
I	T1 N0 M0	The tumor is less than 2 centimeters (cm) across and is still just in the pancreas (T1). The cancer has not spread to nearby lymph nodes (N0) or distant parts of the body (M0).
II	T2 N0 M0	The tumor is at least 2 cm across but no more than 4 cm across, and it is still just in the pancreas (T2). The cancer has not spread to nearby lymph nodes (N0) or distant parts of the body (M0).
	OR
	T3 N0 M0	The tumor is more than 4 cm across and is still just in the pancreas, OR the tumor has grown into the duodenum (the first part of the small intestine) or the common bile duct (T3). The cancer has not spread to nearby lymph nodes (N0) or distant parts of the body (M0).
III	T4 N0 M0	The tumor has grown into nearby organs (such as the stomach, spleen, colon, or adrenal gland) or it has grown into nearby large blood vessels (T4). The cancer has not spread to nearby lymph nodes (N0) or distant parts of the body (M0).
	OR
	Any T N1 M0	The tumor can be any size and might or might not have grown outside the pancreas (any T). It has spread to nearby lymph nodes (N1), but not to distant parts of the body (M0).
IV	Any T Any N M1	The tumor can be any size and might or might not have grown outside the pancreas (any T). It might or might not have spread to nearby lymph nodes (any N). The cancer has spread to distant parts of the body (M1).

* The following additional categories are not listed in the table above: 

• TX: The main tumor cannot be assessed due to lack of information. 
• T0: There is no evidence of a main tumor.
• NX: Nearby lymph nodes cannot be assessed due to lack of information. 

Other prognostic factors for pancreatic neuroendocrine tumors (pNETs)

Although not formally part of the TNM system, other factors can also be important in determining a person’s prognosis (outlook).

Tumor grade

The grade describes how quickly the cancer is likely to grow and spread. For pNETs, an important part of grading is measuring how many of the cells are in the process of dividing into new cells. This is determined by:

• The mitotic count: The number of cells seen under a microscope that are in the process of splitting into two new cells (mitosis). 
• The Ki-67 index: A measure of the portion of cells that are almost ready to start splitting.

Based on these tests, pNETs are divided into 2 main groups:

• Well-differentiated tumors (which include low-grade [G1] and intermediate-grade [G2] tumors) have 20 or fewer mitoses and a Ki-67 index of 20% or lower. Occasionally a tumor will be well differentiated and have a ki-67 index higher than 20%. Those are considered Grade 3 pNETs.
• Poorly differentiated tumors (high-grade tumors; G3) have more than 20 mitoses or a Ki-67 index of more than 20%. These are also called neuroendocrine carcinomas (NECs), and they often grow and spread quickly.

Tumor functionality

The outlook for pNETs can be affected by whether the tumor is functioning (making hormones) or non-functioning. For functioning tumors, the type of hormone can also be important. For example, insulinomas (pNETs that make insulin) tend to have a lower risk of spreading than other types of pNETs.