Revisiting the Definition of Acral Melanoma: Unraveling Histology and Location

Abstract Acral melanoma (AM) is a rare subtype of melanoma associated with poor prognosis. However, inconsistent definitions—based on either anatomic location (e.g., palms, soles, subungual areas) or histopathologic subtype (e.g., acral lentiginous melanoma)—complicate prognostication, hinder treatment decision-making, and pose challenges for both clinical and translational research. This multi-institutional retrospective cohort study aimed to determine whether anatomic location or histologic subtype better predicts outcomes in AM. Distal extremity primary melanomas (n = 469) were matched 1:2 with cutaneous melanomas (CMs; n = 938). Cox proportional hazards models evaluated recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS). Of the distal tumors, 280 (59.7%) were ALMs, including 33 (11.8%) on non-subungual dorsal sites. Compared to CMs, acral surface melanomas had worse outcomes, while dorsal melanomas had similar outcomes, independent of histology. ALMs were associated with worse survival than superficial spreading melanomas (SSMs). In interaction models, ALMs on dorsal surfaces and all histologic subtypes on acral surfaces had worse MSS than non-distal SSMs. A revised definition of AM may better inform clinical management and future research.