American Melanoma Institute · 5 min read
A rare melanoma unrelated to sun: where it starts, the symptoms that get mistaken for common problems, how its genetics differ, and how doctors treat it.
Pigment cells called melanocytes live in more places than the skin. They are also found in the moist lining, or mucosa, of the nose, sinuses, mouth, anus, rectum, vulva and vagina. Melanoma that starts in these linings is called mucosal melanoma.
About 1 in 100 melanomas is mucosal, according to AIM at Melanoma and Cleveland Clinic. Roughly half begin in the head and neck, and most of the others begin in the anorectal region or the female genital tract. AIM at Melanoma gives a median age at diagnosis of about 70. These melanomas make up a larger share of all melanomas in Asian populations than in white populations.
These surfaces never see sunlight. Ultraviolet light is not a proven risk factor, and researchers have not identified a clear cause or a way to prevent mucosal melanoma. No habit or exposure on the patient's part explains it.
Mucosal melanomas grow out of sight, and their early symptoms mimic conditions that are far more common. That is the main reason diagnosis tends to come late.
Nearly everyone with these symptoms has something benign. The useful rule is persistence. A symptom on 1 side of the nose that lasts more than a few weeks, rectal bleeding that continues despite hemorrhoid treatment, or any new pigmented spot in the mouth or on the genitals merits a direct look by a specialist and, if anything appears abnormal, a biopsy. Some mucosal melanomas have little or no pigment, so a lack of color does not rule melanoma out.
A pathologist makes the diagnosis from a biopsy, using special stains that identify melanocytes. Part of the workup is a full skin and eye exam, because a melanoma in a mucosal site can occasionally be spread from a primary tumor somewhere else.
CT, MRI or PET scans then map how far the tumor extends and whether it has reached lymph nodes or distant organs. Staging differs by location. Head and neck mucosal melanoma has its own staging system, while tumors at other sites are staged with systems adapted to those sites. Skin melanoma rules such as Breslow thickness do not carry over directly.
About half of skin melanomas carry a BRAF mutation. Mucosal melanomas carry BRAF mutations much less often, so BRAF and MEK inhibitor pills help only a small share of patients. Changes in a gene called KIT are more common in mucosal melanoma than in skin melanoma, although published estimates of how common vary widely.
Doctors therefore order molecular testing on mucosal melanomas that are advanced. When a KIT mutation of a sensitive type is present, drugs such as imatinib (Gleevec) or nilotinib (Tasigna) can shrink the tumor. The American Cancer Society lists these drugs as options for melanomas with KIT changes. Responses occur in a minority of patients and often do not last, so these drugs usually come after immunotherapy.
Mucosal melanomas also carry fewer total mutations than sun-damaged skin melanomas. Fewer mutations give the immune system fewer targets, which may explain why immunotherapy works less often here.
Surgery to remove the tumor completely offers the best chance of control when the disease is confined to 1 area. Anatomy makes this hard. A wide margin in the sinuses, the anal canal or the vagina can mean a major operation, and surgeons weigh the benefit against the effect on breathing, continence or sexual function. For anorectal melanoma, many surgeons now prefer a more limited excision when it can clear the tumor.
Radiation after surgery is common in the head and neck to lower the chance of the tumor returning in the same place. For disease that has spread or cannot be removed, checkpoint inhibitor immunotherapy is the main treatment, the same drugs used for skin melanoma. Response rates are lower than in skin melanoma, and some patients still have long-lasting responses.
The large trials of drug treatment after surgery mostly left out mucosal melanoma, so doctors have limited evidence for that decision and discuss it case by case. Because the disease is rare, NCCN and patient organizations encourage treatment at a center with melanoma and site-specific surgical expertise, and clinical trials deserve a look at every stage.
Mucosal melanoma has a less favorable outlook than skin melanoma. Doctors usually find it later, it sits in places where complete removal is difficult, and it tends to return and spread even after successful surgery. Published 5-year survival figures range from under 20% to about 25% across all sites and stages combined, and they vary by location and by how early the tumor was found.
Those figures have limits. They come from small studies that span many years, and many of the patients were treated before current immunotherapy was available. They describe groups and cannot predict what will happen to any single person. Tumors found small and removed completely do much better than the averages suggest. Your own team, with your stage and pathology in hand, can give a more meaningful estimate than any published number.
