Acral melanoma foot lesions. Part 1: epidemiology, aetiology, and molecular pathology

Abstract

Acral melanoma (AM) is a rare subtype of cutaneous malignant melanoma (MM) found on acral skin, primarily on the soles of the feet. Although rare, it is the most common subtype of MM found in patients of African or East Asian ethnicity and has a poor prognosis, often because of the more advanced stage of presentation at diagnosis. The pathogenesis of AM is unclear, but genetic alterations, including mutations in BRAF, NRAS, and KIT have been implicated. Early diagnosis of AM is important for a better prognosis, but its identification is often challenging, leading to easy misdiagnosis. In the first of this two-part review, we review the history, epidemiology, aetiology and molecular pathology of AM; in part 2 we will review diagnosis and management.

Prognostic features for acral lentiginous melanoma

“…In populations of European origin where melanoma incidence is highest, ALM is one of the least common cutaneous melanoma histological subtypes, accounting for < 10% of cases . However, among people with more heavily pigmented skin, who experience lower melanoma incidence rates, ALM may account for up to 50% of cases of melanoma .…”

“…The actual incidence rates of ALM are similar for all ethnicities, because unlike other types of cutaneous melanoma, the aetiology of ALM is largely unrelated to sun exposure . The pathogenesis of ALM remains largely unknown, although injury to the site or mechanical stress may play a role . Whole‐genome sequencing has shown that the development of ALM is driven by structural changes and mutation signatures of unknown aetiology …”

“…Compared with other histological subtypes of cutaneous melanoma, ALM is typically detected at a relatively late stage and has a poor prognosis . Prognostication for melanoma is based on the American Joint Committee on Cancer (AJCC) stage of disease, which incorporates data on Breslow thickness, ulceration, mitoses, lymph node involvement and metastases.…”

“…2 However, among people with more heavily pigmented skin, who experience lower melanoma incidence rates, ALM may account for up to 50% of cases of melanoma. 2 The actual incidence rates of ALM are similar for all ethnicities, 3 because unlike other types of cutaneous melanoma, the aetiology of ALM is largely unrelated to sun exposure. 4 The pathogenesis of ALM remains largely unknown, although injury to the site or mechanical stress may play a role.…”

“…4 The pathogenesis of ALM remains largely unknown, although injury to the site or mechanical stress may play a role. 2,5,6 Whole-genome sequencing has shown that the development of ALM is driven by structural changes and mutation signatures of unknown aetiology. 4 Compared with other histological subtypes of cutaneous melanoma, ALM is typically detected at a relatively late stage and has a poor prognosis.…”