Neuroendocrine Tumors: Grades

Approved by the Cancer.Net Editorial Board, 05/2022

ON THIS PAGE: You will learn about how doctors describe how fast the tumor cells are growing and dividing, called the grade or degree of differentiation. Use the menu to see other pages.

Doctors may describe a neuroendocrine tumor (NET) by its World Health Organization (WHO) grade (G). Knowing the grade helps the doctor create a treatment plan for the NET. "Grade" and "stage" may be mentioned at the same time while NETs are being discussed, but they are very different elements in understanding the risk a tumor poses to a person. This section covers grading for NETs. The WHO grades for NETs include:

  • Grade 1 (low-grade tumor): These cells divide at a low rate and therefore grow slowly.

  • Grade 2 (intermediate-grade tumor): These cells divide at an intermediate rate.

  • Grade 3 (high-grade tumor): These cells divide at a fast rate and therefore grow quickly.

Grade is determined by both the mitotic count and Ki-67, which are both markers of how fast the tumor cells grow and divide. To determine the mitotic count, the doctor counts the number of dividing cells seen in a specific amount of space under a microscope (2 mm2). The doctor also measures 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.

Grade

Mitotic Count

Ki-67

Grade 1

Less than 2

Less than 3%

Grade 2

2 to 20

3% to 20%

Grade 3

More than 20

More than 20%

For many types of cancer, the grade also describes how much cancer cells look like healthy cells when viewed under a microscope, called degree of differentiation.

  • Well differentiated: The cells are well differentiated, which means they look more like healthy cells.

  • Poorly differentiated: The cells are poorly differentiated, which means they look less like healthy cells. Poorly differentiated neuroendocrine carcinomas (NECs) are divided into large-cell and small-cell type, which refers to what the cells look like under the microscope. They are treated the same.

The tumor’s grade and degree of differentiation may help the doctor predict how quickly the NET will grow and spread. In general, the lower the tumor’s grade and degree of differentiation, the better a person’s prognosis.

More detailed information about grading for a specific type of NET can be found in each specific NET section. See the Introduction for a list of those NETs by name.

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.