Abstract 5083: Distinct clinical and molecular features of acral melanoma in a diverse urban population including very low incidence of brain metastasis: Insights from a Bronx cohort in NYC

Abstract Introduction: Acral melanoma (AM) is a rare melanoma subtype that disproportionately affects minority populations. AM has distinct clinical and molecular features compared with non-acral cutaneous melanomas (NACM). The Bronx has an underserved diverse population anda relatively high incidence of AM and therefore we sought to define key features of AM in this population. Methods: A retrospective chart review was conducted at Montefiore Medical Center (MMC, Bronx, NY) of patients diagnosed with melanoma from 1984-2024, identifying 550 patients; clinical, pathologic, treatment, and outcome data were extracted. Statistical comparisons used the Mann-Whitney U test for continuous/ordinal variables and chi-square for categorical variables or Fisher’s exact test if any value was less than 10. P-values <0.05 were considered statistically significant. Unpublished Data: Compared with TCGA, MMC patients were older (median 68.0 vs. 58.0, p<0.001) and more often female (45.0% vs. 38.3%, p=0.038). There was a higher proportion of Hispanics (19.5% vs. 2.3%) and African Americans (8.3% vs. 0.2%), as well as a greater percentage of AM cases (17.0% vs 0.4%) (all p<0.001). At MMC, patients with AM presented at significantly higher stages compared to those with NACM (p=0.010). Conversely, brain metastases developed in 0% of AM cases as compared with 22.2% (p=0.002) of NACM. BRAF mutations were found in 18.1% of AM cases versus 34.1% of NACM cases for whom data was available. Among patients with >12 months follow-up receiving immune checkpoint blockade (ICB) for stage III-IV disease, AM patients had a lower durable rate of response (>12 months) to ICB (11.1% vs 33.3%). Durable response correlated strongly with overall survival (p=0.005). No difference in overall survival was observed between patients diagnosed with AM and those with NACM. RNA expression profiling using the NanoString platform across Roswell, ECOG, and MMC cohorts demonstrated a statistically significant downregulation of CCL27, a chemokine critical for T-cell recruitment, in AM versus NACM. Tissue analysis revealed AMs had a significantly higher median myeloperoxidase (MPO) proportion (p=0.011) and a trend toward a reduced CD8/MPO ratio (p=0.066), suggesting altered tumor microenvironment. Conclusions: Our dataset highlights key differences in disease presentation, tumor biology, and outcomes of AM, underscoring the need to expand national databases for diverse populations including Hispanics and African Americans because patterns of progression may differ from AM in more homogeneous populations in East Asia or Europe. Presentation at more advanced stages coupled with the absence of brain metastases and a unique tumor micro-environment suggest a need for tailored management of diverse populations with AM in the US. Citation Format: Katherine Kovrizhkin, Tianyun Jiang, Matan Uriel, Emily Nadelmann, Katia Papalezova, Beth N. McLellan, Jee-Young Moon, Yvonne Saenger. Distinct clinical and molecular features of acral melanoma in a diverse urban population including very low incidence of brain metastasis: Insights from a Bronx cohort in NYC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5083.