Decoding Your Pathology: Grading and Staging Your G-NET

Your pathology report is the most important document in your medical record. It is the result of a pathologist looking at your tissue under a microscope to determine exactly what the “personality” of your tumor is. For gastric neuroendocrine tumors (G-NETs), the report must answer three main questions: What kind of cell is it? How fast is it growing? And how far has it gone? ^[1][2]

1. Differentiation: The “Family”

The first thing to look for is differentiation. This describes how much the tumor cells look like healthy, normal cells.

• Well-Differentiated (NET): These tumors look fairly similar to normal hormone-producing cells. They are typically less aggressive and have a better prognosis ^[3][4]. Note: Even well-differentiated tumors can sometimes grow quickly (NET G3), but they are still biologically distinct from poorly differentiated tumors.
• Poorly Differentiated (NEC): These cells look very abnormal and disorganized. By definition, all poorly differentiated tumors are high-grade and aggressive “carcinomas” (NECs) ^[5][6].

2. Grade: The “Speed”

Grading tells you how fast the tumor cells are dividing. This is measured in two ways:

• Ki-67 Index: This is a “proliferation marker.” Pathologists use a special stain to see what percentage of cells are in the process of dividing. A Ki-67 of 2% means 2 out of every 100 cells are dividing ^[7][6].
• Mitotic Rate: This is a manual count of how many cells are caught in the middle of dividing (mitosis) within a specific area of the slide ^[3].

The WHO 2019 Grading Scale for Gastric NETs:

*A well-differentiated tumor with a Ki-67 over 20% is classified as a “Well-Differentiated NET G3.” It is important not to confuse this with a poorly differentiated NEC, as their treatments and underlying biology are different ^[4].

Note: If your report has a Ki-67 that places you in G2 but a mitotic rate that places you in G1, doctors usually use the higher grade to be safe ^[8].

3. Staging: The “Extent” (TNM)

Staging describes how far the tumor has spread. The TNM system is the standard used by doctors:

• T (Tumor): Measures the size of the tumor and how deep it has grown into the layers of the stomach wall. Confining the tumor to the top layers (mucosa or submucosa) is a positive sign ^[9][10].
• N (Node): Indicates if the tumor has spread to nearby lymph nodes.
• M (Metastasis): Indicates if the tumor has spread to distant organs, most commonly the liver ^[11].

Your Pathology Audit Checklist

Every G-NET pathology report should ideally include these data points. If any are missing, you should ask your doctor if they can be added through further testing.

• [ ] Differentiation: (Well-differentiated vs. Poorly-differentiated) ^[1]
• [ ] Ki-67 Index: (The percentage, e.g., 4%) ^[7]
• [ ] Mitotic Rate: (Number of mitoses per 2mm²) ^[3]
• [ ] Tumor Size: (Usually in mm or cm) ^[10]
• [ ] Invasion Depth: (How deep it goes into the stomach wall) ^[9]
• [ ] Margin Status: (Whether the edges of the removed tissue are clear of “cancer”)
• [ ] Lymphovascular Invasion: (Whether the tumor has started to enter local blood or lymph vessels)

If Ki-67 or mitotic rate is missing, it is considered essential for modern care. These markers are indispensable for deciding whether you need simple monitoring or more active treatment ^[7][12].