Mitotic rate
Dermal mitoses per mm²; mitotic count; mitotic index
Mitotic rate (mitoses per mm² of the dermal invasive component) is an established independent prognostic factor in melanoma. Although it was removed as a T1 sub-classifier in AJCC 8 (replaced by the 0.8 mm Breslow threshold for T1a vs T1b), it remains clinically relevant: NICE NG14 uses mitotic index ≥ 2 as one factor supporting SLNB discussion for melanomas 0.8–1.0 mm thick, alongside ulceration and LVI. It remains a reported component of the RCPath melanoma dataset. Counting is performed in the dermal invasive component, in a 1 mm² area centred on the hotspot.
Counting methodology
- Identify the area of the dermal invasive melanoma with the highest density of mitoses ("hot spot").
- Count mitotic figures in a 1 mm² area (or measured equivalent — typically 5 high-power fields at 40×, depending on microscope field-of-view calibration; field diameter must be calibrated).
- Report as mitoses per mm² (e.g. 2/mm², 5/mm²).
- Count only definitive mitoses; exclude apoptotic figures and pyknotic nuclei.
- For very small lesions where 1 mm² of dermal component is not present, report mitoses in the entire dermal component and note the limitation.
Role in AJCC 8 and NG14
- AJCC 8 — mitotic rate is not part of the T1 sub-classification (which uses Breslow alone: T1a < 0.8 mm, T1b 0.8–1.0 mm or < 0.8 mm with ulceration).
- NICE NG14 §1.4.3–1.4.4 — consider SLNB for Breslow 0.8–1.0 mm melanoma if ulceration, LVI or mitotic index ≥ 2 is present, and for Breslow > 1.0 mm after discussion of benefits and risks.
- Mitotic rate ≥ 1 / mm² remains an independent prognostic factor in multivariate models even in thin melanoma.
- RCPath melanoma dataset — mitotic rate per mm² is a required reporting item.
Clinical implications
- SLNB discussion — mitotic index ≥ 2 is one of the NG14 adverse features, alongside ulceration and LVI, that supports SLNB discussion for 0.8–1.0 mm melanoma.
- Adjuvant therapy discussions — high mitotic rate alongside other adverse features (ulceration, LVI, PNI) may influence MDT discussion in stage IIA / IIB.
- Follow-up cadence — high-mitotic-rate stage II melanoma may be discussed at MDT for more intensive surveillance.
- Inter-observer variability is modest but not negligible — specialist dermatopathology review for borderline cases.
Pitfalls
- Field-size calibration — older "high-power field" reporting is unreliable across microscopes; the field-area-based mm² reporting is now standard.
- Confusing mitoses with apoptotic figures or pyknotic nuclei — count only convincing mitotic figures (metaphase, anaphase, telophase).
- Single-section sampling may miss localised hotspots in heterogeneous lesions.
- Mitotic rate is part of a multivariable prognostic picture — interpret with Breslow, ulceration, LVI, PNI, microsatellites, lymphocyte infiltrate, regression.
References
- Thompson JF et al. Prognostic significance of mitotic rate in localized primary cutaneous melanoma — pooled analysis. J Clin Oncol; 2011.
- Gershenwald JE et al. Melanoma staging — AJCC 8th edition. CA Cancer J Clin; 2017.
- NICE NG14. Melanoma: assessment and management. London: NICE; 2015 (updated 27 July 2022), recommendations 1.4.3-1.4.4.
- Royal College of Pathologists. Dataset for histopathological reporting of primary cutaneous malignant melanoma and regional lymph nodes (G125). London: RCPath; February 2019.
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