NET disease classification and stages
NETs, like any tumor, are ‘graded’ based on the European Neuroendocrine Tumour Society (ENETS) and World Health Organisation (WHO) systems: low (Grade 1/G1), intermediate (Grade 2/G2) or high (Grade 3/G3). The grades represent the speed at which the tumor grows – the higher the grade, the faster the tumor grows. Grading the tumor helps doctors establish the best plan for managing a NET2.
A pathologist determines a given tumor’s grade after carefully examining a biopsy (sample of the tumor tissue) under a microscope. The grading is based on several criteria, including the Ki-67 index, which is a measure of how quickly the tumor cells are dividing. Suppose a high percentage of cells (>20%) are positive for Ki-67 in a particular area of a tumor tissue sample; in that case, the cells are dividing (also known as proliferating) quickly, and therefore the tumor is growing rapidly.

Another criterion for tumor grading is the state of differentiation of the tumor cells, which indicates how abnormal cancer cells look compared to the surrounding healthy cells. Well-differentiated tumor cells look like nearby healthy cells and tissue organization is normal. Poorly-differentiated tumors have abnormal-looking cells and may lack typical tissue structures. Poorly-differentiated tumors tend to grow and spread quicker than well-differentiated tumor cells.

Cancer stage refers to the extent of cancer, depending on how large the tumor is, as well as whether it has spread to other areas of the body (metastasized). Staging varies for different types of tumors, but most guidelines recommend a system of four stages, with stage 4 indicating metastasis or spreading to distant areas of the body3.
