Stroma AReactive Invasion Front Areas (SARIFA) is associated with dissemination-related histopathological features in...

Stroma AReactive Invasion Front Areas (SARIFA) is a histopathological pattern of tumor-adipocyte interaction not previously evaluated in melanoma. We aimed to define melanoma-adapted SARIFA criteria and evaluate their associations with dissemination-related histopathological features in fifty Clark level V cutaneous melanomas. SARIFA was defined as direct contact between adipocytes and a cluster of at least five melanoma cells at the invasive front, without intervening stroma or inflammatory reaction. Associations with clinicopathological variables were assessed using the Mann-Whitney U and Fisher's exact tests, and a multivariable model evaluated the SARIFA-lymphovascular invasion association after adjustment for Breslow thickness and ulceration. Reproducibility was assessed using Cohen's kappa. SARIFA was identified in 24 of 50 cases (48%). SARIFA-positive tumors showed greater Breslow thickness (p = 0.015) and more frequent ulceration (p = 0.035), and were associated with lymphovascular invasion (p < 0.001; OR, 10.37; 95% CI, 2.42-56.39) and microsatellitosis (p = 0.015; OR, 7.39; 95% CI, 1.27-79.81). In the multivariable model, SARIFA remained associated with lymphovascular invasion after adjustment for Breslow thickness and ulceration (OR, 7.22; 95% CI, 1.82-33.50; p = 0.0068). Interobserver and intraobserver agreement were substantial (κ = 0.64; 95% CI, 0.38-0.90) and almost perfect (κ = 0.84; 95% CI, 0.69-0.99), respectively. SARIFA was associated with lymphovascular invasion and microsatellitosis, and the association with lymphovascular invasion was maintained in multivariable analysis. Melanoma-adapted SARIFA may represent a reproducible histopathological pattern linked to dissemination-related tumor behavior, although validation in larger cohorts with clinical outcome data is required.