# Mucosal melanoma

Source: https://onco.cc/cancers/mucosal-melanoma/  
OnCo record `mucosal-melanoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Mucosal melanoma grows on the moist linings of the nose, mouth, anus or genital tract rather than on sun-exposed skin, so it is found late and carries fewer of the mutations that make skin melanoma visible to the immune system. Immunotherapy helps less often than in skin melanoma; a minority of tumours has a KIT mutation that the pill imatinib can target.

## Summary

Mucosal melanoma arises from melanocytes in the sinonasal tract, oral cavity, anorectum, vulva, vagina and, rarely, the urinary tract, biliary tree and oesophagus. It is not caused by ultraviolet light and its genome differs from cutaneous melanoma: a low mutation burden, frequent structural rearrangements and amplifications, KIT mutations or amplifications in a substantial minority, SF3B1 mutations, and BRAF V600 mutations in only about one in twenty. Presentation is late because the sites are hidden, and most patients have thick, often ulcerated or multifocal primaries; five-year survival is well below that of cutaneous melanoma at any stage.

Surgery is the mainstay for localised disease, but local recurrence is frequent and radical operations at head and neck or anorectal sites carry heavy morbidity, so postoperative radiotherapy is often added to improve local control even though it has not lengthened survival. In China, where the disease is common, a randomised trial found adjuvant temozolomide-cisplatin chemotherapy improved relapse-free and overall survival over high-dose interferon and observation, and it remains an option there. Sentinel node biopsy is less standardised than in cutaneous disease.

Immunotherapy works less well than in cutaneous melanoma: in the pooled analysis of the nivolumab trials the response rate was 23 percent with nivolumab alone and 37 percent with nivolumab plus ipilimumab, and pembrolizumab produced responses in 19 percent in the pooled KEYNOTE analysis. Chinese investigators combined toripalimab with the VEGF receptor inhibitor axitinib and reported responses in nearly half of chemotherapy-naive patients in phase 1b, and the pairing is being tested in randomised trials. Imatinib produces responses in roughly one in four tumours with KIT exon 11 or 13 mutations, and the MEK inhibitor tunlametinib is approved in China for NRAS-mutant melanoma, a group that includes many mucosal tumours.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Melanoma of mucous membranes; Sinonasal melanoma; Oral mucosal melanoma; Anorectal melanoma; Vulvovaginal melanoma
- Tags: subtype-page
- Group: skin
- Burden: Mucosal melanoma is about one in a hundred melanomas in Europe and North America but roughly a fifth of melanomas in China, where it is the second commonest subtype; it arises in the nose and sinuses, mouth, anus and rectum, and vulva and vagina, and is usually found late.
- Subtypes: Sinonasal and oral mucosal melanoma (head and neck); Anorectal mucosal melanoma; Vulvar and vaginal mucosal melanoma; KIT-mutant mucosal melanoma (imatinib candidates); NRAS-mutant mucosal melanoma (MEK inhibitor trials); Mucosal melanoma in East Asian populations (toripalimab-axitinib approach)
- Biomarkers: KIT mutation or amplification (exon 11 and 13 predict imatinib response); NRAS mutation; BRAF V600 mutation (uncommon); SF3B1 mutation; Low tumour mutational burden; PD-L1 expression (weakly predictive)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/mucosal-melanoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/mucosal-melanoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/mucosal-melanoma/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/mucosal-melanoma/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/mucosal-melanoma/#treating-it [5 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/mucosal-melanoma/#evidence [3 trials, 6 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/mucosal-melanoma/#science [6 targets, 1 pathway]
- Countries and centres (own page): 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. https://onco.cc/cancers/mucosal-melanoma/where-you-are/ [10 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/mucosal-melanoma/#living-with-it [19 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/mucosal-melanoma/coming/ [13 medicines, 1 trial, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/mucosal-melanoma/data/ [50 connected records]

## Standard of care

- Localised disease: Wide surgical excision with the least morbid operation that clears margins; postoperative radiotherapy for head and neck and anorectal primaries to improve local control. ([Wide local excision](https://onco.cc/terms/wide-local-excision/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Adjuvant: Anti-PD-1 antibody as for cutaneous stage III disease by extrapolation; temozolomide-cisplatin chemotherapy is an option in China on a randomised trial. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Cisplatin](https://onco.cc/drugs/cisplatin/))
- Advanced, first line: Nivolumab plus ipilimumab (higher response than nivolumab alone in the pooled analysis) or anti-PD-1 monotherapy; toripalimab with axitinib in China. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Toripalimab](https://onco.cc/drugs/toripalimab/), [Axitinib](https://onco.cc/drugs/axitinib/))
- KIT-mutant disease: Imatinib for exon 11 or 13 mutations after or alongside immunotherapy; nilotinib is an alternative. ([Imatinib](https://onco.cc/drugs/imatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [KIT](https://onco.cc/targets/kit/))
- NRAS-mutant disease: Tunlametinib (approved in China) or MEK inhibitor trials; naporafenib with trametinib in the SEACRAFT-2 trial. ([Tunlametinib](https://onco.cc/drugs/tunlametinib/), [Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma](https://onco.cc/trials/nct06008106/), [A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)](https://onco.cc/trials/seacraft-2/), [Naporafenib](https://onco.cc/drugs/naporafenib/))

## State of the art

- Immunotherapy doublets produce responses in about a third of patients, roughly half the rate seen in cutaneous melanoma.
- KIT is the one recurrent drug target and imatinib the one approved kinase inhibitor that works in a subset.
- China, where the disease is common, leads the trials of immunotherapy combined with anti-angiogenic drugs.

## Open problems

- No phase 3 trial has been run specifically in mucosal melanoma outside China.
- Local control at head and neck and anorectal sites is poor without mutilating surgery.
- The low mutation burden limits immunotherapy and there is no approved drug for the common structural alterations.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Mucosal_melanoma
- Pooled nivolumab analysis in mucosal melanoma (JCO 2017): https://ascopubs.org/doi/10.1200/JCO.2016.67.9258
- Toripalimab plus axitinib (JCO 2019): https://ascopubs.org/doi/10.1200/JCO.19.00210
- Wikipedia: https://en.wikipedia.org/wiki/Mucosal_melanoma

## Connected records

- cancers: [Acral melanoma](https://onco.cc/cancers/acral-melanoma/), [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Conjunctival melanoma](https://onco.cc/cancers/conjunctival-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/), [Melanoma of the urethra](https://onco.cc/cancers/urethral-melanoma/), [Uveal melanoma](https://onco.cc/cancers/uveal-melanoma/), [Vaginal melanoma](https://onco.cc/cancers/vaginal-melanoma/), [Vulvar cancer](https://onco.cc/cancers/vulvar/), [Vulvar melanoma](https://onco.cc/cancers/vulvar-melanoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [CTLA-4](https://onco.cc/targets/ctla4/), [KIT](https://onco.cc/targets/kit/), [MEK1/2](https://onco.cc/targets/mek/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Axitinib](https://onco.cc/drugs/axitinib/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Imatinib](https://onco.cc/drugs/imatinib/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Lifileucel](https://onco.cc/drugs/lifileucel/), [Naporafenib](https://onco.cc/drugs/naporafenib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Toripalimab](https://onco.cc/drugs/toripalimab/), [Tunlametinib](https://onco.cc/drugs/tunlametinib/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- key papers: [Adjuvant temozolomide plus cisplatin versus high-dose interferon versus observation in resected mucosal melanoma](https://onco.cc/key-papers/paper-lian-adjuvant-temozolomide-cisplatin-mucosal-melanoma-ccr-2013/), [Distinct sets of genetic alterations in melanoma](https://onco.cc/key-papers/paper-curtin-melanoma-genetic-alterations-nejm-2005/), [Imatinib for melanomas harbouring mutationally activated or amplified KIT arising on mucosal, acral and chronically sun-damaged skin](https://onco.cc/key-papers/paper-hodi-imatinib-kit-melanoma-jco-2013/), [Nivolumab alone or with ipilimumab in mucosal melanoma: pooled analysis](https://onco.cc/key-papers/paper-dangelo-mucosal-melanoma-pooled-jco-2017/), [Somatic activation of KIT in distinct subtypes of melanoma](https://onco.cc/key-papers/paper-curtin-kit-melanoma-jco-2006/), [Whole-genome landscapes of major melanoma subtypes](https://onco.cc/key-papers/paper-hayward-melanoma-whole-genome-nature-2017/)
- trials: [A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)](https://onco.cc/trials/seacraft-2/), [A Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastat](https://onco.cc/trials/nct06797297/), [Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma](https://onco.cc/trials/nct06008106/)
- terms: [SF3B1 mutation](https://onco.cc/terms/sf3b1-mutation/), [Wide local excision](https://onco.cc/terms/wide-local-excision/)

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JSON: https://onco.cc/api/v1/entities/mucosal-melanoma.json