Acral melanoma

Uncommon, atypical form of melanoma that arises on the volar and subungunal surfaces.

Sites of involvement include palms,soles and nail beds.

Comprises only 2-10% of all melanomas.

They comprise only 1 to 2% of all melanomas  in Western Caucasian populations.

Most frequent type of melanoma in in those of African, Middle Eastern, and Asian descent.

Acral melanomas predominates and accounts for approximately 40% of cases in Asian populations.

Compared to cutaneous, melanoma, acral melanomas present with more aggressive, biologic behavior, with distinct genetic profiles characterized by a lower tumor mutation burden.

AMs make up a large proportion of melanomas in Blacks, Asians, and Hispanics due to the low incidence of UV mediated melanomas in these ethnic groups.

Acral melanomas comprise 40-45% of cases of melanoma in China and Japan.

Frequently misdiagnosed because of its uncommon location and lack of a changing mole.

Over 2/3 of a AMs are diagnosed at stage II or above compared to 1/3 of cutaneous melanomas.
Early detection is complicated by difficulty in distinguishing early malignant melanomas from benign melanocytic nevus, the rarity of the tumor, often occult sites of origin, pigmentation of the lesions can follow the skin markings of the palms and soles, concealing the lesion and further hindering early diagnosis.
Numerous cases of AM have been misdiagnosed such as fungal infections or nonhealing traumatic wounds.
Dermoscopy has improved the diagnostic accuracy and early detection of AM
Confers a worse overall prognosis compared to cutaneous melanomas; this negative effect is not clear in Asian studies.
The five-year overall survival for AM is inferior to that of cutaneous melanomas overall 80.3% and 91.3%, respectively.
Caucasians with AM have the highest five-year survival rate, followed by blacks, Hispanics, and Asian//Pacific Islanders.

It is molecularly distinct from cutaneous melanoma, harboring higher rates of rearrangements such as copy number gains and losses and lower rate of ultraviolet induced missense mutations and BRAF V600 alterations.

Frequently amelanotic and ulcerated.

Most common location of foot and ankle melanomas is on the plantar aspect of the foot.

Poorer prognosis for foot and ankle melanomas.

KIT mutations occur more commonly than in cutaneous melanomas 15-20% versus 1%.

BRAF mutations arise less often in acral versus cutaneous melanoma, 15% versus 45-50%.

NRAS mutations were found in cutaneous and acral melanoma with the similar incidence of 15-20%.

Standard treatment is wide local excision.
 Because of the location of the lesions, amputation is often needed for subungual melanomas or plastic surgery is involved for lesions of the palms/soles which may lead to prolonged recovery.

Presently the addition of targeted therapies and immunotherapy have altered treatment practice.

Ipilimumab is an active agent in acral melanoma.

Overall responds great to immune checkpoint blockade is 32%, similar or slightly lower than that seem in cutaneous melanoma.

BRAF mutations only occur in 10 to 22% of patients with acral melanomas, and KRAS 9 to 28% limiting the use of targeted agents.

KIT variants are found in mucosal, and a acral melanomas, but have a  low frequency of 10 to 20% and KIT inhibitors only have limited activity.


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