Acral Lentiginous Melanoma: A Comprehensive Review of Epidemiology, Pathophysiology, Clinical Presentation, and Therapeutic Advances

Acral lentiginous melanoma (ALM) is a distinct and aggressive subtype of melanoma that disproportionately affects individuals with darker skin tones, representing a unique clinical and biological entity within the broader spectrum of cutaneous melanoma. Although ALM accounts for a relatively small percentage of melanomas globally, it is the most common subtype in non-Caucasian populations. The pathogenesis of ALM is characterized by genetic alterations distinct from other melanoma subtypes, often involving mutations in KIT and focal amplifications, rather than BRAF or NRAS mutations. Clinically, ALM frequently arises on acral surfaces, including palms, soles, and subungual regions, often presenting at an advanced stage due to delayed diagnosis. This review aims to provide a detailed examination of the epidemiology, molecular pathophysiology, clinical manifestations, and diagnostic approaches of ALM, while also highlighting emerging therapeutic strategies, including surgical management, targeted therapy, and immunotherapy. Recognizing the unique challenges associated with ALM is critical for improving early detection, tailoring treatment strategies, and ultimately enhancing patient outcomes.