Pancreatic NET (PanNET) Grading

About this calculator

Grades well-differentiated pancreatic neuroendocrine tumors using mitotic rate per 2 mm² and Ki-67 index, per the CAP Pancreatic Endocrine Tumor protocol. The higher of the two grades determines the final result.

Site scope. This calculator is specific to pancreatic NETs. Duodenal/ampullary, jejunal/ileal, gastric, and colorectal NETs are addressed by their own separate CAP protocols, which may carry site-specific notes not included here.

Necrosis — reported separately, not part of this grading formula. High mitotic rate, high Ki-67 index, and tumor necrosis have all been shown to correlate strongly with aggressive behavior. However, the WHO grading table used by this calculator (Section below) is defined using only mitotic rate and Ki-67 index. Necrosis should still be documented in the pathology report as a relevant adverse feature, but it does not factor into the G1/G2/G3 calculation here.

Grading thresholds

Exact boundaries, never rounded before comparison. 1.99 → G1; 2.00 → G2; 20.00 → G2; 20.01 → G3. Same convention for Ki-67 at 3% and 20%. Final grade = higher of the two — never averaged. Necrosis is not part of this table (see the necrosis note on the Calculator tab).

Mitotic rate

Only clearly identifiable mitotic figures are counted; hyperchromatic, karyorrhectic, or apoptotic nuclei are excluded. Assess the most mitotically active area, evaluating at least 10 mm².

Ki-67 proliferation index

Reported as percent positive tumor cells in the area of highest nuclear labeling (the hot spot).

Methodology is not standardized. Automated counting and manual "eyeballing" are both used. Eyeballing can be used for most tumors. For a Ki-67 index close to a grade cutoff (near 3% or near 20%), a manual count on a print of a camera-captured image of the hot spot is recommended rather than eyeballing alone. A minimum of 500 tumor cells is recommended; note if fewer were available.

Field diameter reference table

Generated dynamically from A = π(d/2)², not from stored values. Your current diameter is highlighted. This protocol's own source table uniquely also lists HPF required for 2 mm² directly — reproduced here as a dynamically computed column.

Values are computed from the formula; differences of about ±1 HPF from the published CAP table can occur due to rounding conventions in the source document. Calculations in this app always use the unrounded formula result, not the table.

Well-differentiated NET-G3 vs. poorly differentiated NEC

There is a recognized subgroup of well-differentiated neuroendocrine tumors with a Ki-67 index >20% — and a mitotic rate usually <20 per 10 HPF — that nonetheless retain typical well-differentiated morphology rather than the morphology of a poorly differentiated neuroendocrine carcinoma (NEC).

Under WHO-2010, these tumors were classified as G3 poorly differentiated neuroendocrine carcinomas. Studies specifically on pancreatic neuroendocrine tumors demonstrated that these tumors have a worse prognosis than grade 2 (Ki-67 3–20%, mitosis <20/10 HPF) NETs, but are not as aggressive as poorly differentiated NEC. Under the WHO-2022 Blue Book of Endocrine Tumours and AJCC 9th edition, tumors with typical well-differentiated morphology are instead classified as well-differentiated neuroendocrine tumor, G3 — a biologically distinct entity from NEC:

• Worse prognosis than G2 NET, but better prognosis than NEC

• Distinct underlying genetics from NEC

• Reduced responsiveness to platinum-based chemotherapy compared with NEC

This calculator determines the numeric grade (G1/G2/G3) from mitotic rate and Ki-67 only. It cannot and does not distinguish well-differentiated NET-G3 from poorly differentiated NEC. That distinction is based on tumor morphology — architecture and nuclear features — and requires direct pathologist evaluation. A numeric G3 result must be paired with morphologic assessment before rendering a final diagnostic category.

The "<20 per 10 HPF" figure above is a descriptive characterization from the literature, not a separate formal grading input — the only mitotic input in this calculator is the field-diameter-based mitoses-per-2-mm² measurement on the Calculator tab. No input field, checkbox, or toggle in this calculator attempts to make the NET-G3-vs-NEC determination algorithmically — it is intentionally out of scope.

Sources

1. WHO Classification of Tumours Editorial Board. Endocrine Tumours. 5th ed. Lyon, France: IARC; 2022.

2. AJCC Cancer Staging Manual, 9th edition. American College of Surgeons.

3. College of American Pathologists (CAP). Protocol for the Examination of Specimens From Patients With Tumors of the Endocrine Pancreas (document Panc.Endo_5.0.1.0.REL_CAPCP).

The source protocol excerpt carries in-text citation markers (numbered up to at least 11) for specific claims — including the correlation of mitotic rate, Ki-67, and necrosis with aggressive behavior; Ki-67 counting methodology comparisons; prognosis of the NET-G3 subgroup; its genetic distinction from NEC; and reduced platinum-chemotherapy responsiveness — whose full bibliographic entries were not available when this app was built (the excerpt ended at the "References" heading without the list itself). Those specific citations are not fabricated here — consult the complete published protocol for exact references. The historical WHO-2010 classification is mentioned for context only and is superseded by the current edition cited above.

Educational and decision-support tool only. Does not replace the current WHO classification, AJCC staging, CAP protocol, institutional protocol, or professional pathologist judgment — particularly for distinguishing well-differentiated NET-G3 from poorly differentiated NEC, which requires direct morphologic evaluation.