Grade, stage, and Ki-67

Differentiation describes appearance

Differentiation refers to how tumor cells look and are organized. For digestive neuroendocrine cancers, well-differentiated NET and poorly differentiated NEC are distinct categories. A well-differentiated tumor can still be high grade. Classification requires the pathologist's assessment, rather than a Ki-67 result alone. NANETS: High-grade neuroendocrine neoplasm consensus recommendations

Grade describes proliferative activity

For well-differentiated gastroenteropancreatic NETs, grade uses measurements of tumor-cell proliferation:

• Ki-67 index: the percentage of sampled tumor cells staining for a protein associated with cell proliferation.
• Mitotic rate: the number of visibly dividing cells within a defined tissue area.

The Ki-67 ranges used for these NETs are below 3% for grade 1, 3% through 20% for grade 2, and above 20% for grade 3. Mitotic rate also matters. When both measurements are available and differ, the higher grade generally determines classification. This is a gastroenteropancreatic NET grading framework; ask your team which framework applies to your tumor site. CAP: Pancreatic neuroendocrine tumor reporting protocol

Stage describes location and spread

Stage describes the extent of cancer, including the primary tumor, nearby lymph nodes, and distant spread. The TNM system records these features separately. Stage IV generally means the cancer has spread to distant parts of the body.

Stage IV does not automatically mean grade 3. A tumor can have a low grade and still have spread. Conversely, a high-grade tumor need not have distant metastases when diagnosed. This distinction follows from what stage and grade measure. NCI: Cancer staging

Put the results back into context

Ask how the tissue findings, including differentiation and Ki-67, fit with imaging. Your care team can explain the full picture. Ki-67 alone is not a survival estimate. NCI: Pancreatic NET diagnosis and staging