What is differentiation?
Differentiation describes how closely the tumour resembles normal neuroendocrine tissue under the microscope.
- A well-differentiated neuroendocrine tumour, or NET, still has recognisable neuroendocrine structure.
- A poorly differentiated neuroendocrine carcinoma, or NEC, looks more abnormal and is biologically different.
NET and NEC are not simply slower and faster versions of one disease. They can have different behaviour, treatment and evidence. A high-grade well-differentiated NET is therefore not automatically the same as a poorly differentiated NEC.
What does grade describe?
Grade describes how actively the tumour cells are proliferating. For many gastroenteropancreatic NETs, the pathologist uses the mitotic count and Ki-67 index.
The broad categories are grade 1, grade 2 and grade 3. Higher grade generally indicates more active cell division, but the exact cut-offs and terminology depend on the classification for that primary site.
If mitotic count and Ki-67 point to different grades, the pathology team follows the relevant classification rules. The final grade should be taken from the pathology report rather than estimated from symptoms or scan growth alone.
What is Ki-67?
Ki-67 is a protein found in cells that are dividing. A pathologist uses a stain and reports the percentage of tumour cells labelled in the assessed area. This is the Ki-67 index.
For many digestive-system NETs, current classifications use thresholds around 3% and 20% to help separate grades. These numbers should not be applied indiscriminately to every neuroendocrine neoplasm. Lung and thymic tumours, for example, have site-specific criteria in which mitoses and necrosis have established roles and Ki-67 is not used in exactly the same way.
Ki-67 is also a sampled measurement. Different areas of a tumour or different tumour sites can occasionally have different levels of proliferation. The pathologist selects and assesses the most informative tissue available.
What does stage describe?
Stage describes the anatomical extent of the cancer: the primary tumour, nearby lymph nodes and spread to distant sites. The staging system depends on the organ where the NET started.
Grade and stage answer different questions. A low-grade NET can be metastatic, and a higher-grade NET can be localised. Neither number should be read as a substitute for the other. The general distinction is explained in Cancer stage and grade: what is the difference?.
Why do all these features matter?
Treatment planning may consider:
- the primary site;
- differentiation and grade;
- Ki-67 and mitotic rate;
- stage and distribution of disease;
- whether the tumour produces hormones;
- somatostatin-receptor imaging;
- symptoms, growth over time and previous treatment;
- general health and personal priorities.
This is why a single Ki-67 number does not determine the whole plan.
What if the pathology wording is unclear?
It is reasonable to ask whether the diagnosis is a well-differentiated NET or a poorly differentiated NEC, which grading system was used, and whether the sample is adequate. Specialist pathology review can be helpful when the classification is uncertain or treatment depends on a fine distinction.
Questions to ask
- Where did the neuroendocrine tumour start?
- Is it well differentiated or poorly differentiated?
- What are the grade, Ki-67 index and mitotic rate?
- Which site-specific classification has been used?
- What is the stage, and how was it established?
- Which of these features most influences the treatment recommendation?
NET terminology is detailed because these tumours are diverse. Keeping differentiation, grade, Ki-67 and stage separate makes the pathology report easier to understand and avoids treating one number as the whole diagnosis.
