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Clinical calculator summary

WHO 2019 GEP-NET Grade

Histologic grade based on the higher available proliferation grade from Ki-67 index and mitotic rate.

Evidence-based context for fast calculator use

Purpose:
Reproduce the WHO 2019 grade for well-differentiated gastroenteropancreatic NETs.
Population:
Pathologically confirmed, well-differentiated gastroenteropancreatic neuroendocrine tumors.
Factors:
Ki-67 hotspot index, Mitotic rate per 2 mm², Higher-grade discordance rule, Tumor differentiation and site
Reference:
WHO Classification of Digestive System Tumours, fifth edition, 2019.
HomeNET Grade / WHO 2019
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NET Grade / WHO 2019

Optional
%

Optional when a normalized mitotic rate is available; at least one proliferation measure is required.

Optional
per 2 mm²

Optional when a Ki-67 hotspot index is available; at least one proliferation measure is required.

Clinical Context & Background

This calculator implements the 2019 WHO Classification of Digestive System Tumours grading system for pathologically confirmed, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Ki-67 index and mitotic rate are graded independently, and the higher available grade is assigned when they differ.
Ki-67 should be assessed in the highest-labeling hotspot, generally by counting at least 500 tumor cells. Mitotic rate should be normalized to 2 mm2; CAP recommends examining at least 10 mm2. A fixed number of high-power fields must not be assumed equivalent to 2 mm2 without microscope field-area correction. Raw, unrounded values determine thresholds.
This is histologic grading, not staging, individualized prognosis, or treatment selection. It does not apply automatically to poorly differentiated small-cell or large-cell neuroendocrine carcinoma (NEC), MiNEN, or pulmonary, thymic, head-and-neck, thyroid, pituitary, adrenal, or paraganglionic tumors. NET G3 remains biologically and diagnostically distinct from poorly differentiated NEC. Limited biopsy material may underestimate the highest proliferative area, and differentiation should be reported separately from grade.
Primary Source EvidenceWHO Classification of Tumours Editorial Board. Digestive System Tumours. 5th ed. IARC; 2019. Nagtegaal ID, et al. Histopathology. 2020;76:182-188. College of American Pathologists neuroendocrine tumor protocols.
Formula Logic
Grade Ki-67 and mitotic rate independently using WHO 2019 digestive-system NET thresholds, then assign the higher available grade: Ki-67 <3% = G1, 3-20% = G2, >20% = G3; mitoses <2/2 mm2 = G1, 2-20/2 mm2 = G2, >20/2 mm2 = G3.

Reference Data

GradeMitotic rate (per 2 mm²)Ki-67 index
G1<2<3%
G22-203-20%
G3>20>20%

Clinical Workflow

Use, Interpret, And Continue The Patient Pathway

Expand for workflow guidance, limitations, examples, and related next steps.

When To Use

  • For pathologically confirmed, well-differentiated gastroenteropancreatic NET.
  • Use at least one adequately assessed proliferation measure; report both when available.

How To Interpret

  • Ki-67 <3% or mitoses <2/2 mm² is G1; 3-20% or 2-20/2 mm² is G2; values >20 are G3.
  • When measures are discordant, assign the higher grade and retain both measurements in the pathology report.

What To Do Next

  • Confirm Ki-67 hotspot counting and mitotic-area normalization.
  • Integrate grade with differentiation, primary site, stage, specimen adequacy, and multidisciplinary assessment.

Limitations

  • Not validated here for NEC, MiNEN, or non-digestive neuroendocrine neoplasms.
  • Limited biopsy may miss the highest proliferative area.
  • Histologic grade does not independently select treatment or provide individualized prognosis.

Validated Population

Well-differentiated gastroenteropancreatic NETs within the WHO 2019 digestive-system classification.

Discordant proliferation measures

Ki-67 10% is G2 and mitotic rate 25/2 mm² is G3, so the final grade is G3.

Calculation verification history

Verified

  1. : Production browser revalidation

    • Five source-backed WHO 2019 GEP-NET grade cases were exercised on the public production route through visible controls; 5/5 expected grades matched across both Ki-67 thresholds and a discordant-marker branch.
    • No unexpected N/A, literal undefined value, stale control, or browser-console error was observed.
    Download latest production check (Excel)

    Case-level evidence is retained in validation/browser-revalidation/neuroendocrine-tumor-grade-who-2019-2026-08-03.json.

  2. : Local browser remediation verified; production retest pending

    • Ten source-backed cases were exercised through visible controls on the corrected local route; 10/10 passed across 11 submissions.
    • Single-measure submissions now work when the other optional control is absent from form state. Exact Ki-67 and mitotic boundaries, higher-grade discordance, invalid blank submission, and reset/repeat behavior all matched the WHO 2019 oracle.
    • The original production failure remains retained and open until this commit is deployed and the public route is revalidated.

    Case-level local remediation evidence is retained in validation/browser-production/neuroendocrine-tumor-grade-who-2019.local-remediation.json.

  3. : Production browser validation

    • Ten source-backed cases were exercised on the public production route through visible browser controls; 1/10 case records passed their expected-versus-observed assertions across 11 visible submissions.
    • Overall browser status: failed-calculation-ui-and-console. critical: Production marks both proliferation measures required and blocks every source-supported Ki-67-only or mitotic-rate-only submission, although the verified model permits either adequately assessed measure alone. | high: The valid two-measure discordant case returned Grade 3 but displayed literal `undefined` after both the Ki-67 and mitotic-rate trace rows. | medium: Production emitted minified React error #418 during route loads/reloads used by this run.
    • Case-level inputs, expected and observed results, reset/repeat behavior, failure reproductions, and console evidence are retained in the production-browser evidence record.

    Case-level production evidence is retained in validation/browser-production/neuroendocrine-tumor-grade-who-2019.json.

  4. : Full validation test

    • 256/256 source, independent-oracle, boundary, discordance, invalid-input, UI, trace, scope, registry, and report checks passed.
    • This verifies implementation of the selected WHO 2019 grade, not independent clinical validation, staging, individualized prognosis, or treatment selection.

  5. : Calculation, input, and scope correction

    • Enforced raw WHO thresholds, exact-20 G2 boundaries, decimal mitotic rates per 2 mm2, and the higher-grade discordance rule without blank-to-zero coercion.
    • Restricted use to well-differentiated gastroenteropancreatic NET and added NEC, MiNEN, non-digestive-site, specimen, hotspot, and microscope-area cautions.

Verification confirms the calculator implementation against the cited model; it is not independent clinical validation, regulatory approval, or medical advice.

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Frequently Asked Questions

What happens when Ki-67 and mitotic grades differ?

The higher available grade is assigned. The detailed result shows both component grades.

Is a mitotic count per 10 HPF interchangeable with per 2 mm²?

Not automatically. Microscope high-power fields vary in area, so the rate must be normalized using the measured field area.

Is NET G3 the same as poorly differentiated NEC?

No. A well-differentiated NET G3 is distinct from poorly differentiated small-cell or large-cell neuroendocrine carcinoma.

Evidence-based oncology decision support. Verify with clinical guidelines.