Acral melanoma
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.
Overview
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.
State of the art
- Treatment is extrapolated from cutaneous melanoma trials in which acral tumours were a small minority.
- Response rates to PD-1 blockade are lower and the subtype's amplification-driven biology has no approved drug yet.
- Chinese and Japanese cohorts, where the subtype is common, now supply most of the evidence.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowFainting or palpitations (ribociclib)
Fainting, dizziness or an irregular heartbeat; QT prolongation is a labelled warning and ECGs are checked in the first cycles.
- Check before combiningFood and drink: Dabrafenib + trametinib
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
- Check before combiningFood and drink: Imatinib
Take with a meal and a large glass of water.
- Check before combiningFood and drink: Palbociclib
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
Anatomy and lymph node drainage
- Epidermis (in situ)
- Basal layer (melanocytes, basal cells)
- Keratinocytes (squamous)
- Dermis (invasive; Breslow depth)
- Merkel cells (dermal-epidermal)
- Dermal vessels (Kaposi)
- Acral and mucosal sites
- Nodes: sentinel node in the draining basin
- Nodes: regional basin (axilla, groin, neck)
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.
- Epidermis (in situ)
- Basal layer (melanocytes, basal cells)BRAF V600-mutant acral melanoma (targeted therapy eligible)
- Keratinocytes (squamous)
- Dermis (invasive; Breslow depth)
- Merkel cells (dermal-epidermal)
- Dermal vessels (Kaposi)
- Acral and mucosal sitesAcral lentiginous melanoma of the sole (commonest site) · KIT-mutant acral melanoma (imatinib candidates) · BRAF V600-mutant acral melanoma (targeted therapy eligible) · CDK4 pathway-amplified acral melanoma (CDK4/6 inhibitor trials)
- sentinel node in the draining basin
- regional basin (axilla, groin, neck)
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, Dermatofibrosarcoma protuberans
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.
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
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.
Subtypes & biomarkers
top- Acral lentiginous melanoma of the sole (commonest site)
- Subungual melanoma (nail apparatus, often with Hutchinson sign)
- Palmar melanoma
- KIT-mutant acral melanoma (imatinib candidates)
- BRAF V600-mutant acral melanoma (targeted therapy eligible)
- CDK4 pathway-amplified acral melanoma (CDK4/6 inhibitor trials)
How often this target appears
- 1976Reed describes acral lentiginous melanoma as a distinct subtype
- 2005Curtin and Bastian: distinct genetic pattern with few mutations and many amplifications in acral melanoma
- 2011Imatinib phase 2 trials in KIT-mutant melanoma, many of them acral
- 2020Japanese multicentre series: 17 percent response to anti-PD-1 in acral melanoma
- 2024Tunlametinib approved in China for NRAS-mutant melanoma
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 7 changes by month →- 2026-09-17This recordAcral melanomaFacts on this page last checked
When this page itself was last checked or edited.
- 2024Trial resultNADINANADINA reported
12-month EFS 83.
- 2024MilestoneTunlametinibTunlametinib approved in China for NRAS-mutant melanoma
A milestone in how this cancer is treated.
- 2020MilestoneNivolumabJapanese multicentre series: 17 percent response to anti-PD-1 in acral melanoma
A milestone in how this cancer is treated.
- 2011MilestoneImatinibImatinib phase 2 trials in KIT-mutant melanoma, many of them acral
A milestone in how this cancer is treated.
- 2005MilestoneKITCurtin and Bastian: distinct genetic pattern with few mutations and many amplifications in acral melanoma
A milestone in how this cancer is treated.
What is in development for Acral melanoma, drawn from the whole corpus: 3 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Technologies being tested · 1
Trials under way · 2
- Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma · phase 3 · Shanghai Kechow Pharma, Inc.
- A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2) · phase 3 · Erasca
Open problems and what is being done
Late diagnosis remains the main cause of poor outcomes and awareness in people with darker skin is low.
and how the field plans to fix it →What is being done about thisFinding cancer earlierAvailable nowNothing recorded yet.
In trialsIdeas and roadmapsNothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
No trial has been designed for acral melanoma alone outside East Asia.
The amplification-driven genome offers targets (CDK4, CCND1) without a proven drug.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Milan · cancer center | Italy | none recorded | 0 | 1,246 | 21,746 | #11 | |
Amsterdam · cancer center | Netherlands | none recorded | 1 | 1,451 | 25,873 | #45 | |
Tampa, FL · cancer center | United States | 0 | 2,580 | 31,111 | - | ||
Los Angeles · cancer center | United States | 0 | 2,019 | 32,934 | - | ||
Vienna · cancer center | Austria | none recorded | 0 | 1,266 | 17,145 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - | |
Brussels · cancer center | Belgium | none recorded | 0 | 489 | 8,689 | - | |
Seoul · hospital | South Korea | none recorded | 0 | 448 | 2,611 | - | |
Kyoto · hospital | Japan | none recorded | 0 | 251 | 1,942 | - | |
Navi Mumbai · research institute | India | none recorded | 0 | 175 | 1,127 | - | |
Philadelphia, PA · consortium | United States | none recorded | 0 | 165 | 1,237 | - | |
Tokyo · hospital | Japan | none recorded | 0 | 139 | 708 | - | |
Lebanon, NH · cancer center | United States | 0 | 112 | 687 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Acral melanoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Acral melanoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Breslow thickness and ulceration, BRAF V600 mutation, NRAS mutation, KIT mutation or amplification, CCND1, CDK4 and TERT amplification), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Acral lentiginous melanoma of the sole, Subungual melanoma, Palmar melanoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Why: Guideline options include: 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.
Localised disease
- For my situation (localised disease), which of the standard options do you recommend and why?Why: Guideline options include: Wide local excision with thickness-based margins, distal amputation for subungual disease when needed, sentinel lymph node biopsy for primaries over 0.8 mm.
Resected stage III
- For my situation (resected stage iii), which of the standard options do you recommend and why?Why: Guideline options include: Adjuvant nivolumab or pembrolizumab; dabrafenib-trametinib for BRAF V600-mutant disease; neoadjuvant immunotherapy for macroscopic nodes as in NADINA.
- Am I a candidate for Nivolumab, Pembrolizumab, Dabrafenib + trametinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NADINA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced disease
- For my situation (advanced disease), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Tunlametinib, Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma, Palbociclib, Imatinib?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Late diagnosis remains the main cause of poor outcomes and awareness in people with darker skin is low”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No trial has been designed for acral melanoma alone outside East Asia”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Acral melanoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
7targets
6drugs
8companies
6pathways
1terms
3trials
3Latest papers
topQuery 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.
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