High Mitotic Index for Melanoma
A mitotic rate >6/mm² is considered high for melanoma, with rates >11/mm² conferring particularly poor prognosis, reducing 5-year melanoma-specific survival to 84% in node-negative patients. 1
Prognostic Thresholds by Clinical Context
The definition of "high" mitotic rate varies based on tumor thickness and clinical application:
For Thin Melanomas (T1, ≤1.0 mm)
- Mitotic rate >2/mm² is clinically significant and represents an adverse feature that increases risk of sentinel lymph node (SLN) positivity 1
- This threshold should prompt discussion of sentinel lymph node biopsy even in T1a lesions (Breslow depth <0.8 mm, non-ulcerated) 1
- In non-ulcerated T1 melanomas, mitotic rate ≥2/mm² significantly increases both SLN positivity and recurrence risk compared to lower rates 2
For General Prognostic Stratification
- The NCCN guidelines identify mitotic rate >11/mm² as a critical threshold that substantially worsens melanoma-specific survival across all thickness categories (T1-T4) 1
- Historical AJCC staging categorized mitotic rates as: <1-6, and >6/mm², with >6/mm² emerging as an independent poor prognostic factor in multivariate analysis 1
For Intermediate Thickness Melanomas
- Mitotic rate ≥4/mm² for T2 tumors (1.01-2.0 mm) represents elevated proliferative activity associated with higher recurrence risk 2
- Mitotic rate ≥6/mm² for T3 tumors (2.01-4.0 mm) indicates aggressive biology 2
Clinical Implications of High Mitotic Rate
High mitotic rate melanomas demonstrate distinct clinical and pathologic characteristics:
- More common in elderly men (≥70 years) with cumulative solar damage history 3
- Predilection for head and neck location 3
- Frequently present as amelanotic (non-pigmented) lesions 3
- Associated with rapid growth rate (≥2 mm/month) 3
- Strongly correlated with nodular melanoma subtype, greater tumor thickness, and ulceration 3
Measurement Technique
Mitotic rate must be measured using the "hot spot" technique:
- Count mitoses in the area of highest mitotic activity 1
- Report as number of mitoses per mm² (1 mm² ≈ 3-4 high-power fields at 40× magnification, calibrated for individual microscope) 1
- Record as a whole number per mm² for all T1-T4 melanomas 1
Critical Pitfalls to Avoid
Do not dismiss mitotic rate in thin melanomas: Even in T1a lesions <0.8 mm without ulceration, mitotic rate >2/mm² independently predicts SLN positivity and recurrence, warranting consideration of sentinel lymph node biopsy 1, 2
Do not rely solely on ulceration for risk stratification: In non-ulcerated thin melanomas (T1-T2), elevated mitotic rate is a more reliable predictor of adverse outcomes than ulceration status alone 2, 4
Recognize age-specific considerations: In children and adolescents with melanoma, mitotic rate remains the strongest independent predictor of recurrence-free survival, even more so than Breslow thickness 5