Prognostic Value of a Novel Nuclear Grading of Cutaneous Melanoma

We developed a nuclear grading system for melanoma, the UNC Chapel Hill Method, akin to McGovern's 1970 classification, to evaluate its correlation with disease progression and adverse histologic features, including thickness, mitotic rate, and ulceration. This retrospective study analyzed 544 melanomas diagnosed from 2020 to 2023, with a median follow-up of 411 days; 89 patients experienced progression, and 22 died of disease. A dermatopathologist assigned nuclear grades based on nuclear size, membrane contour, nucleolar features, and chromatin arrangement. Grade 1 resembled nevus nuclei, Grade 3 exhibited marked nuclear abnormalities, and Grade 2 was intermediate. Kaplan-Meier survival analysis demonstrated significantly worse progression-free survival for Grade 3 lesions compared with grades 1 and 2 (P<0.003). Statistical analyses (Student t test, χ2, and Kruskal-Wallis) revealed that grade 3 melanomas were associated with increased age, Breslow thickness, mitotic rate, ulceration, advanced AJCC stage, and mortality (each P<0.05). In a univariate Cox model, grade 2 (HR: 1.7; 95% CI: 0.7-4.0) and grade 3 (HR: 3.6; 95% CI: 1.5-8.4) lesions had an increased risk of progression relative to grade 1. After adjusting for covariates, hazard ratios were attenuated for grade 2 (HR: 1.2; 95% CI: 0.5-2.9) and grade 3 (HR: 1.7; 95% CI: 0.7-4.2). These findings show nuclear grade is associated with melanoma progression, but increased statistical power with longer follow-up and additional cases are needed to assess its independent prognostic value.