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Grades of neuroendocrine cancer

Grading is a way of classifying cancer cells based on their appearance and behaviour when viewed under a microscope. To find out the grade of a tumour, the biopsy sample is examined under a microscope. A grade is given based on how the cancer cells look and behave compared to normal cells (differentiation). This can give the healthcare team an idea of how quickly the cancer may be growing and how likely it is to spread.

Grading proposals for neuroendocrine cancer at each site are still being finalized and there is no widely accepted international standard.

The grade is generally based on:

  • how different the cancer cells look from normal cells (cell differentiation)
  • how frequently the cancer cells are dividing (mitoticmitoticThe process by which a cell divides to form 2 new cells. Each new cell receives a complete set of chromosomes from the original cell. counts and Ki-67 measurements)
  • the cancer’s tendency to spread to new locations

Most grading systems for neuroendocrine cancers broadly follow the outline below:

Grade I

well-differentiated endocrine tumour, slow growth rate

Grade II

well-differentiated endocrine carcinoma, intermediate growth rate

Grade III

Poorly differentiated endocrine carcinoma, aggressive growth rate

There are varying terms and classifications for neuroendocrine tumours or carcinomas, which sometimes cause confusion. The term carcinoidcarcinoidA tumour that starts in cells of the neuroendocrine system. has been applied to well-differentiated neuroendocrine tumours that are benign or potentially malignant. It has also been used to describe malignant neuroendocrine cancers in the stomach, intestine, appendix, rectum and lungs. For this reason, it is no longer recommended as a diagnostic term to describe a neuroendocrine tumour. It is now used only to describe carcinoid syndrome and some types of lung neuroendocrine tumours.

In 2000, the World Health Organization (WHO) adopted a new classification based on the characteristics of the tumour cells. The WHO’s classification suggested replacing the word "neuroendocrineneuroendocrineReferring to or having to do with the neuroendocrine system or the cells and organs that make up this system." with "endocrineendocrineA type of gland without a duct that releases hormones directly into the blood." for tumours in the lung and pancreas, but this has not been accepted for the GI tract.

The WHO classification of neuroendocrine tumours in the digestive system and pancreatic islet cells has yet to gain uniform acceptance in Canada. Gastrointestinal and pancreatic neuroendocrine tumours are named based on the type of cell the cancer develops in and the type of hormone secreted. The WHO system for neuroendocrine tumours of the digestive system and pancreas does not apply to tumours that develop in the adrenal medulla or paraganglia.

WHO classification of endocrine tumoursDescription

Well-differentiated endocrine tumours

benign endocrine tumours (non-cancerous growths that do not spread to other parts of the body) or potentially malignant endocrine tumours  that have only a small chance of spreading

Well-differentiated endocrine carcinomas

slow-growing tumours that can spread; cancer cells closely resemble normal endocrine cells

Poorly differentiated endocrine carcinomas

aggressive tumours that are likely to spread; cancer cells are different from normal endocrine cells and grow quickly

Mixed exocrine-endocrine tumours

tumours have both endocrine (without ducts) and exocrine (with ducts) gland cells

behaviour varies depending on the type of tumour and how different the cancer cells are from normal exocrine or endocrine gland cells

Along with the type and extent (stage) of the cancer, grading plays an important part in planning neuroendocrine cancer treatment. Grading can also be used to help estimate the prognosis (future outcome).


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