Does anatomical subsite matter in acral melanoma?: A cohort study of clinical and molecular features.

Abstract

e21595 Background: Acral melanoma is a rare and biologically distinct melanoma subtype, frequently diagnosed at advanced stages and associated with a low prevalence of actionable molecular alterations. Whether anatomical subsite within acral locations influences tumor aggressiveness and clinical outcomes remains uncertain, particularly in real-world cohorts from Latin America. Methods: We retrospectively analyzed patients with pathologically confirmed acral melanoma treated at a A.C. Camargo Cancer Center, Brazil, between 2020 - 2025. Among 196 patients initially evaluated with a clinical suspicion of acral melanoma, 57 cases were histologically confirmed and included. Primary anatomical location was classified by site and subsite. Survival outcomes were estimated using Kaplan–Meier methods, and associations between anatomical subsite, clinicopathological features and outcomes were explored using log-rank tests and logistic regression analyses. Results: Median age: 59 years (IQR 51–71) and 59% of patients were female. Primary tumors were most frequently located on the plantar surface of the foot (56%), followed by non-ungual digital sites (29%), subungual melanoma (7%), other acral non-plantar/non-digital sites (3.5%) and other locations (3.5%). At diagnosis, 43% of tumors were T3–T4, nodal involvement was present in 14% and distant metastasis in 1.8%. Somatic mutations were detected in 10.5% of cases [ BRAF V600E (8.8%) and KIT (1.8%)]. During follow-up, metastatic progression occurred in 24.6% of patients and local recurrence in 10.5%. The 60-month progression-free survival (PFS) was 73.1% (95% CI, 57.9–92.3) and overall survival (OS) at 60 months was 89.2% (95% CI, 79.7–99.9%). No statistically significant differences in PFS or OS were observed according to primary anatomical location. Exploratory analyses by anatomical subsite demonstrated a trend toward more advanced clinical stage (II–IV) in tumors arising from the plantar heel (global p = 0.062). In multivariable analysis adjusted for ulceration, anatomical subsite was not independently associated with advanced stage, whereas ulceration remained a strong predictor (OR 10.5, 95% CI 2.50–57.7). When stratified by clinical stage, patients diagnosed at advanced stages (II–IV) had significantly worse overall survival compared with those diagnosed at early stages (IS–I) (log-rank p = 0.03). A non-significant trend toward worse progression-free survival was observed in advanced-stage disease (log-rank p = 0.13). Conclusions: Anatomical subsite was not independently associated with survival outcomes in this cohort of acral melanoma. However, plantar heel tumors showed exploratory signals of more advanced presentation, largely mediated by ulceration. Advanced clinical stage was significantly associated with worse overall survival, underscoring the importance of early diagnosis in acral melanoma.