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Acral melanoma grows on the soles, palms or under a nail, places without sun exposure, and it is the commonest melanoma in people with darker skin. It is often mistaken for a wart, bruise or fungal nail and so found late; treatment follows skin melanoma, but immunotherapy works less often because the tumour carries fewer mutations.
Acral melanoma arises on the glabrous skin of the palms, soles and nail apparatus and is not caused by ultraviolet light; its genome has few point mutations but frequent amplifications of CCND1, CDK4 and TERT and other structural changes. BRAF V600 mutations occur in about one in six tumours, NRAS in a similar share and KIT alterations in around one in ten. Delay in diagnosis is the rule, since lesions are mistaken for warts, calluses, haematomas or fungal nail infection, and thick, ulcerated primaries with nodal spread are common at presentation; stage for stage, outcomes are somewhat worse than for other cutaneous melanomas.
Management follows cutaneous melanoma: excision with margins set by thickness, which for digits may mean amputation of the distal phalanx, sentinel node biopsy for primaries over 0.8 millimetres, and adjuvant anti-PD-1 antibody or, for BRAF-mutant disease, dabrafenib-trametinib after resection of stage III disease. Reconstruction of weight-bearing soles is a particular surgical problem. No adjuvant or advanced-disease trial has been run in acral melanoma alone; the evidence is extrapolated from trials in which acral tumours were a small minority.
Response to PD-1 blockade is lower than in melanoma of sun-damaged skin: a Japanese multicentre series of 193 patients found responses in 17 percent, and a United States series found responses in about a third. Combination immunotherapy is preferred where tolerated. Imatinib produces responses in roughly a quarter of KIT-mutant tumours, tunlametinib is approved in China for NRAS-mutant melanoma, and CDK4/6 inhibitors are being tested against the CDK4 pathway amplifications that characterise the subtype.
Acral melanoma arises on the palms, soles and under the nails; its absolute incidence is similar in every population, so it is a small minority of melanomas in people with fair skin but the commonest melanoma subtype in people of African and Asian ancestry, accounting for about four in ten melanomas in China.
Each skin cancer comes from a different cell layer: melanocytes and basal cells at the base of the epidermis, keratinocytes above them, Merkel cells and blood vessels in the dermis; depth of invasion decides the risk.
Same organ: Melanoma, Basal cell carcinoma, Cutaneous squamous cell carcinoma, Merkel cell carcinoma, Kaposi sarcoma, Skin cancer (all types), BRAF V600-mutant melanoma, Stage III melanoma (after surgery), Stage IIB and IIC melanoma, Advanced melanoma (unresectable stage III and stage IV), Mucosal melanoma, Advanced cutaneous squamous cell carcinoma, Locally advanced and metastatic basal cell carcinoma, Bowen's disease (squamous cell carcinoma in situ), Dermatofibrosarcoma protuberans
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
Dermoscopy of the parallel ridge pattern and biopsy of any changing pigmented lesion of the palm, sole or nail; nail matrix biopsy for longitudinal melanonychia with Hutchinson sign.
Wide local excision with thickness-based margins, distal amputation for subungual disease when needed, sentinel lymph node biopsy for primaries over 0.8 mm.
Adjuvant nivolumab or pembrolizumab; dabrafenib-trametinib for BRAF V600-mutant disease; neoadjuvant immunotherapy for macroscopic nodes as in NADINA.
Nivolumab plus ipilimumab or anti-PD-1 monotherapy; BRAF-MEK inhibitors for BRAF-mutant tumours; imatinib for KIT-mutant tumours; tunlametinib for NRAS-mutant disease in China; trials of CDK4/6 inhibitors.
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Patients with melanoma that has spread to palpable lymph nodes should now be offered immunotherapy before rather than only after surgery: two cycles of low-dose ipilimumab with nivolumab, then surgery, with the pathology result deciding whether any more treatment is needed. Most patients respond well and are spared a year of adjuvant therapy. Serious side effects are more common than with nivolumab alone, mostly endocrine, and the approach requires close coordination between oncologists, surgeons and pathologists.
Acral melanoma needs its own treatment evidence: anti-PD-1 monotherapy has limited activity, so combination immunotherapy, KIT-directed therapy and trials of CDK4/6 inhibitors are important options.
The lower response of acral and mucosal melanoma to immunotherapy and the interest in KIT and CDK4/6 inhibitors for these subtypes follow from this genomic picture.
KIT testing is worthwhile in mucosal and acral melanoma, and imatinib is a guideline option for exon 11 or 13 mutations after or alongside immunotherapy.
KIT joined BRAF and NRAS as a melanoma driver and became the rationale for imatinib and nilotinib in mucosal and acral melanoma.
This paper founded the site-based molecular classification of melanoma that underpins separate pages for acral and mucosal disease and their different treatment responses.
Query for this cancer: (TITLE:"Acral melanoma" OR ABSTRACT:"Acral melanoma" OR TITLE:"Acral lentiginous melanoma" OR ABSTRACT:"Acral lentiginous melanoma" OR TITLE:"Melanoma of the palms, soles and nail beds" OR ABSTRACT:"Melanoma of the palms, soles and nail beds" OR TITLE:"Subungual melanoma" OR ABSTRACT:"Subungual melanoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Acral melanoma, not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Fainting, dizziness or an irregular heartbeat; QT prolongation is a labelled warning and ECGs are checked in the first cycles.
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Take with a meal and a large glass of water.
Capsules: take with food (PPIs lower capsule exposure when fasting). Tablets: with or without food. Avoid grapefruit.
See all on the product pages:Dabrafenib + trametinibImatinibIpilimumabNivolumabPalbociclibPembrolizumabTunlametinib·Printable cards in the navigator
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