Thin Nevus-Associated Melanoma: Beyond MIA Score Risk Stratification

Background: Nevus-associated melanomas (NAM) are frequently diagnosed at an early stage, yet risk heterogeneity within thin tumors remains poorly characterized. Whether classical histopathologic features can refine risk stratification in this subgroup is unclear. Objective: To evaluate the prognostic significance of histopathologic features, particularly mitotic activity and tumor-infiltrating lymphocytes (TILs), in thin nevus-associated melanoma (pTis-pT1a) (<0.8 mm). Methods: Retrospective cohort study of 138 consecutive patients with histologically confirmed NAM diagnosed at a tertiary dermatologic oncology center (October 2006-December 2023). Staging was reassessed as per AJCC 8th edition. A predefined subgroup analysis of 100 patients with thin NAM (pTis-pT1a) evaluated adverse outcomes (distant metastasis or death) within 10 years. Associations were assessed using χ² tests and logistic regression. Results: Median age was 53.5 years (IQR 44.0-63.8); 60.9% were male. Median Breslow thickness was 0.57 mm (IQR 0.4-0.8). Overall survival was 90.9% at 5 years and 86.0% at 10 years. Among thin NAM, eight patients (8%) experienced adverse outcomes. Mitotic activity ≥ 1/mm² was associated with higher adverse event rates (10.9% vs. 2.8%; OR, 4.30; 95% CI, 0.51-36.43; p = 0.18). A gradient was observed across TIL categories: adverse events occurred in 13.8% with absent TILs, 7.3% with non-brisk, and 0% with brisk TILs (p = 0.24). Exploratory multivariable analysis showed consistent effect directions without reaching statistical significance. Conclusions: Thin nevus-associated melanomas are not uniformly low risk. Mitotic activity and absent TILs were associated with higher adverse event rates, suggesting that classical histopathologic features may refine risk stratification in early-stage NAM.