Prognostic significance of histopathologically assessed tumor mitotic rate in T1–T4 cutaneous melanoma in the AJCC 8th edition era (2018–2022)

Abstract Cutaneous melanoma (CM) is a highly metastatic malignancy where accurate risk stratification is vital for prognosis. Although tumor mitotic rate (TMR) was removed from T1 staging in the AJCC 8th edition, it remains a critical marker of proliferation. This study utilizes the SEER database (2018–2022) to evaluate the prognostic significance of a five-tier TMR stratification across T1–T4 categories, providing a contemporary assessment of its impact on disease-specific survival (DSS). Data for 85,450 patients aged ≥20 years with malignant CM were extracted from the SEER 17 database (2018–2022). After excluding cases with missing ulceration, TMR, staging, or survival data, TMR was categorized into five tiers (0, 1, 2–3, 4–10, >10 mitoses/mm²). Statistical analyses, performed via IBM SPSS v31.0, included Pearson chi-square tests for baseline characteristics, Kaplan–Meier curves for survival estimation, and multivariable Cox regression to identify independent prognostic factors for DSS across T1–T4 stages. Mitotic activity (TMR ≥1) and ulceration were present in 41.9% and 13.7% of patients, respectively. TMR significantly associated with all clinicopathological variables (p < 0.001). Multivariable analysis revealed nuanced stage-specific patterns: in T1 tumors, TMR became comparable to ulceration at 2–3 mitoses/mm² and surpassed it at ≥4 mitoses/mm², while in T2 tumors, ulceration remained a more potent marker. Conversely, TMR consistently outperformed ulceration across all T3 and T4 categories. A significant stepwise increase in the risk of DSS was observed across higher TMR categories in all T stages. Our findings demonstrate that TMR is an independent prognostic factor whose impact fluctuates by T stage, often rivaling or exceeding the predictive value of ulceration. These results support the integration of multi-tiered mitotic reporting into clinical practice and suggest that refined TMR stratification could enhance the precision of future melanoma prognostic models.