Melanoma is a form of cancer that originates in melanocytes, the pigment-producing cells found primarily in the skin. Mucosal melanoma (MM) is a distinct and aggressive subtype that develops in the moist lining, or mucosa, of various internal body cavities, not the skin. This rare disease accounts for less than 1.4% of all melanoma cases. Because MM often grows in hidden areas, it is typically diagnosed at a more advanced stage than skin melanoma, which contributes to its poorer outlook.
How Mucosal Melanoma Differs from Skin Melanoma
The differences between mucosal melanoma and the more common cutaneous (skin) melanoma are substantial, extending beyond just the location of the tumor. Mucosal melanoma is not associated with exposure to ultraviolet (UV) radiation from the sun, which is the primary cause of most cutaneous melanomas. The underlying causes of MM are not fully understood, but potential factors may include chronic irritation, chemical exposure, or genetic predispositions.
MM is recognized as a biologically more aggressive disease than its cutaneous counterpart. While cutaneous melanoma often features genetic mutations in the BRAF gene, mucosal melanoma displays a more diverse set of genetic alterations, often involving genes like KIT, NRAS, and NF1. The mucosa is a thin, moist layer rich in blood vessels and lymphatic channels, which facilitates the rapid spread of cancer cells to distant sites. This difference in cellular environment and genetic makeup explains why MM often responds differently to treatments originally developed for cutaneous melanoma.
Primary Sites of Occurrence
Mucosal melanomas concentrate in three main anatomical regions. The head and neck area is the most common site, accounting for approximately 50% to 60% of all cases. This region frequently involves the nasal cavity and paranasal sinuses, followed by the oral cavity, particularly the gums, hard palate, and buccal mucosa.
The second most common location is the anorectal and gastrointestinal tract, which accounts for about 20% to 25% of MM diagnoses. Anorectal mucosal melanoma, arising in the anal canal or rectum, is the most frequent presentation here. This site is particularly challenging due to anatomical constraints that complicate surgical removal.
The genitourinary tract represents the third major site of occurrence, comprising approximately 15% to 20% of cases. In women, this includes the vulva and vagina, while in both sexes, the urethra and bladder can be affected.
Recognizing the Symptoms
Symptoms of mucosal melanoma are often vague and depend entirely on the tumor’s location. This lack of specific, early warning signs contributes significantly to the delay in diagnosis. For melanomas in the nasal or sinus cavities, common initial signs include frequent, unilateral nosebleeds (epistaxis) or persistent nasal congestion.
In the oral cavity, the tumor may present as a dark patch—black, brown, or blue—on the gums, palate, or cheek. Patients may notice a non-healing sore, a lump, or bleeding from the mouth tissue.
Lesions in the anorectal area can manifest as a mass, pain, bleeding with bowel movements, or changes in bowel habits that might be mistakenly attributed to hemorrhoids. For genitourinary involvement, symptoms include abnormal bleeding, such as vaginal bleeding between periods or post-menopause, and unusual discharge. A lump or mass in the vulva or vagina, along with persistent itching or pain in the area, should also raise concern. Because these tumors are often painless in their early stages, diagnosis is often delayed until the mass is large or causing functional problems.
Treatment Modalities
The cornerstone of treatment for localized mucosal melanoma is surgical resection, with the goal of achieving complete tumor removal and clear surgical margins. Because MM arises in anatomically complex and delicate locations, obtaining a wide, clean margin can be difficult. Surgical procedures often require complex planning and, in some cases, significant reconstructive surgery to preserve function and appearance.
Radiation therapy is frequently used as an adjuvant treatment following surgery, particularly in cases where achieving clear margins was challenging. While radiation may not improve overall survival, it has been shown to be effective in improving local control and reducing the chance of the cancer returning in the same area. It can also be used as a palliative measure for tumors that are too large or too widespread for surgery.
For advanced or metastatic disease, systemic therapies have become important due to the high rate of distant spread. Immunotherapy, particularly immune checkpoint inhibitors, is a primary systemic approach, although the response rates are generally lower than those seen in cutaneous melanoma. Targeted therapy is also an option for select patients whose tumors show specific genetic mutations, such as those in the KIT gene.