Grading neuroendocrine cancer

Grading describes how the cancer cells look compared to normal, healthy cells. Knowing the grade gives your healthcare team an idea of how quickly the cancer may be growing and how likely it is to spread. This helps them plan your treatment. The grade can also help the healthcare team predict future outcomes (prognosis) and how the cancer might respond to treatment.

The grade helps classify neuroendocrine cancer into neuroendocrine tumour (NET) and neuroendocrine carcinoma (NEC). When talking about the grade, doctors may describe neuroendocrine cancer as a neuroendocrine neoplasm (NEN).

To find out the grade of neuroendocrine cancer, a pathologist looks at a tissue sample from the tumour under a microscope. They look at how different the cells are from normal cells (called differentiation), such as the size and shape of the cells and how the cells are arranged. They can usually tell how fast a tumour is growing by looking at how many cells are dividing.

The following factors help grade neuroendocrine cancer:

• how often the cells of the tumour are dividing (measured as mitotic count)
• the amount of Ki-67 (a specific protein) made during division (measured as a percentage)
• the number of dead cells or tissues that are in the tissue sample (called necrosis)

A neuroendocrine tumour (NET) is well differentiated. This means the cancer cells are abnormal but look a lot like normal cells and are arranged a lot like normal cells. The pathologist gives a NET a grade from 1 to 3. A lower number means the tumour is a lower grade. NETs with a higher mitotic count and a higher Ki-67 percentage are given a higher grade. But the exact cut-off values between the grades may differ depending on where the NET started in the body.

Low-grade (grade 1, or G1) NETs have cancer cells that tend to grow slowly and are less likely to spread.

Intermediate-grade (grade 2, or G2) NETs have cancer cells that tend to grow and divide more quickly than normal cells.

High-grade (grade 3, or G3) NETs have cancer cells that tend to grow quickly and are more likely to spread than G1 or G2 NETs. The cells also look more abnormal compared with G1 or G2 NETs.

A neuroendocrine carcinoma (NEC) is poorly differentiated. This means the cancer cells don’t look like normal cells and are arranged very differently. NECs with small and round cells are called small cell neuroendocrine carcinomas. NECs with large cells are called large cell neuroendocrine carcinomas.

NECs are always high grade (grade 3, or G3). They tend to grow more quickly and spread faster than G3 NETs.