PPGL & PitNET Proliferative Index

Precise mitotic rate and Ki-67 reporting for dynamic risk stratification — no formal WHO grade exists.

Free with an account

Log in to calculate. You can explore the inputs and reference material below; results need a free student account.

This calculator is a pathology decision-support and educational tool for mathematical normalization of mitotic counts and precise reporting of the Ki-67 proliferation index in PPGL and PitNET. It does not assign a grade — none exists for these tumor types — and does not replace the current WHO classification, CAP protocol, institutional protocol, or professional pathologist judgment. Proliferative index is one variable among several used in dynamic risk stratification.

Reference

No formal WHO grade exists for PPGL or PitNET

Unlike epithelial neuroendocrine tumors, there is no G1/G2/G3 system here. Proliferative activity (Ki-67 and mitotic count) is instead an important variable in the dynamic risk stratification of these tumors. The 2022 WHO classification treats proliferation as a continuous variable, not a static threshold — report the precise numeric percentage or count, not a bucketed grade. This calculator deliberately does not output a grade category.

Like epithelial neuroendocrine neoplasms, clinical behavior and prognosis in PPGL are determined in part by growth rate, reflected in Ki-67 labeling and mitotic count. The value of Ki-67 in tumor-related progression and metastasis has also been confirmed in TCGA (The Cancer Genome Atlas) data. However, there is no formal WHO grading system for PPGL — increased proliferative activity is instead an important variable in dynamic risk stratification. The 2022 WHO classification treats proliferation in general as a dynamic variable rather than a static threshold, so a precise numeric percentage or count should be provided for the Ki-67 labeling index or mitotic count of all neuroendocrine neoplasms, PPGL included.

Scope note

The detailed methodology, warnings, and citations in this calculator (Ki-67 hot spot rules, the specific field-diameter table, the CAP document reference) are drawn from the PPGL protocol specifically. PitNET shares the same underlying WHO 2022 principle — proliferation reported as a precise value for dynamic risk stratification rather than a formal grade — so the same calculator is offered for PitNET use. However, PitNET-specific institutional or CAP protocol requirements have not been separately verified here; confirm methodology details (e.g., Ki-67 assessment method, minimum area evaluated) against your own institution's PitNET protocol before relying on this tool for that tumor type.

Ki-67 methodology

Based on the 2022 WHO classification and accuracy studies, Ki-67 assessment from hot spots should be based on a printout of a photo or an automated image analysis algorithm — eyeball estimates are not accurate or acceptable for PPGL. This is a stricter standard than some epithelial NEN sites, where visual estimation is conditionally permitted; do not substitute that more permissive rule here.

PPGLs can show intra-tumoral proliferative heterogeneity. Selecting multiple small hot spots (together totaling at least 500 tumor cells) from different regions of the tumor is often recommended, rather than one larger single-region hot spot.

Mitotic counting methodology

Mitotic rate is reported as mitoses per 2 mm², evaluating at least 10 mm² in the most mitotically active part(s) of the tumor. Only clearly identifiable mitotic figures are counted; hyperchromatic, karyorrhectic, or apoptotic nuclei are excluded.

Hot spot mitotic counting may use contiguous round fields or random fields selected by a randomization method to avoid bias; documenting which method was used is encouraged. Phospho-Histone-H3 (pHH3) immunohistochemistry can also be used to identify mitotic figures.

Field diameter reference table

Generated from A = π(d/2)², not from stored values. Differences of about ±1 HPF from the published CAP table can occur due to rounding conventions in the source document. Calculations always use the unrounded formula result, not the table.

Field diameter (mm)	Area (mm²)	HPF for 10 mm²	HPF for 2 mm²
0.40	0.126	≈80	≈16
0.41	0.132	≈76	≈15
0.42	0.139	≈72	≈14
0.43	0.145	≈69	≈14
0.44	0.152	≈66	≈13
0.45	0.159	≈63	≈13
0.46	0.166	≈60	≈12
0.47	0.173	≈58	≈12
0.48	0.181	≈55	≈11
0.49	0.189	≈53	≈11
0.50	0.196	≈51	≈10
0.51	0.204	≈49	≈10
0.52	0.212	≈47	≈9
0.53	0.221	≈45	≈9
0.54	0.229	≈44	≈9
0.55	0.238	≈42	≈8
0.56	0.246	≈41	≈8
0.57	0.255	≈39	≈8
0.58	0.264	≈38	≈8
0.59	0.273	≈37	≈7
0.60	0.283	≈35	≈7
0.61	0.292	≈34	≈7
0.62	0.302	≈33	≈7
0.63	0.312	≈32	≈6
0.64	0.322	≈31	≈6
0.65	0.332	≈30	≈6
0.66	0.342	≈29	≈6
0.67	0.353	≈28	≈6
0.68	0.363	≈28	≈6
0.69	0.374	≈27	≈5

Sources

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

College of American Pathologists (CAP). Protocol for the Examination of Specimens From Patients With Paraganglioma/Pheochromocytoma (document Paragang_Pheochrom_1.0.0.0.REL_CAPCP).

The source protocol excerpt carries in-text citation markers for specific claims whose full bibliographic entries were not included in the supplied excerpt — consult the complete published protocol for exact references.

Educational and decision-support tool only. Neither PPGL nor PitNET has a formal WHO grade; proliferative index is one input among several used in dynamic risk stratification. PitNET-specific methodology has not been independently verified — confirm against your institution's own protocol.