Melanoma originates in melanocytes, the pigment-producing cells. Mucosal melanoma is a distinct and rare subtype that arises from these same cells, but in the moist lining, or mucous membranes, of internal body cavities. Accounting for approximately 1% to 1.4% of all melanoma cases, this cancer is aggressive and challenging to treat effectively. This article examines its unique characteristics, presentation, diagnosis, and modern management strategies.
How Mucosal Melanoma Differs From Skin Cancer
Mucosal melanoma differs significantly from cutaneous (skin) melanoma, primarily in its etiology. Unlike most skin melanomas, mucosal melanoma is not strongly associated with ultraviolet (UV) radiation exposure. The genetic mutations driving mucosal melanoma are also often different from those found in skin cancers, requiring unique therapeutic approaches. Mucosal melanoma is more aggressive than its cutaneous counterpart and is often diagnosed at a later stage, which contributes to a less favorable prognosis.
Primary sites include the head and neck region (nasal cavity, sinuses, and oral cavity), accounting for about half of all cases. The remaining cases occur mainly in the anorectal region and the female genital tract (vulva and vagina), with a small percentage found in the urinary tract.
Recognizing the Signs and Potential Risk Factors
The signs of mucosal melanoma vary significantly depending on the anatomical location of the tumor. Because the cancer develops in hidden internal areas, symptoms are often non-specific and can mimic those of more common, benign conditions, leading to delayed diagnosis. For tumors in the sinonasal tract, common signs include frequent nosebleeds, chronic nasal obstruction, or the feeling of a persistent mass.
Melanomas in the oral cavity may present as a dark-colored patch, a non-healing ulcer, or a painless mass. If the cancer is located in the anorectal region, a patient might experience rectal bleeding, a mass or lump, or changes in bowel habits. In the vulvovaginal area, symptoms can include abnormal bleeding, discharge, pain, or the presence of a pigmented lesion.
Risk factors for mucosal melanoma are not fully understood, and many cases arise sporadically. The disease is more common in older adults, with the median age of diagnosis around 70 years. Some potential associations have been noted, such as smoking for head and neck mucosal melanomas and chronic irritation or exposure to certain chemicals in industrial settings. Mucosal melanoma is also more prevalent in individuals with darker skin tones compared to cutaneous melanoma.
Confirming the Diagnosis
Once a suspicious lesion or symptom is identified, the diagnostic process begins with a thorough physical examination and imaging studies to determine the extent of the disease. Imaging modalities like computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans are used to assess tumor size and check for spread to nearby lymph nodes or distant organs.
A definitive diagnosis requires a biopsy, where a small tissue sample is surgically removed and examined under a microscope by a specialized pathologist. Pathologists use immunohistochemistry, a technique that employs antibodies to detect specific proteins, to confirm the presence of melanoma cells and distinguish them from other tumor types. Staging mucosal melanoma is complex, often utilizing modified versions of the TNM (Tumor, Node, Metastasis) system, or simplified systems for sites like the anorectal and vaginal areas, since the standard cutaneous melanoma staging does not fully apply.
Modern Treatment Strategies
Treatment for mucosal melanoma is multi-modal, involving a combination of local and systemic therapies. The primary treatment for localized disease remains radical surgical excision, which aims to remove the tumor completely with clear margins of healthy tissue. Due to the complex anatomy of the head, neck, and pelvic regions, achieving wide margins can be difficult.
Radiation therapy is frequently employed after surgery to reduce the risk of the cancer returning in the same area, offering improved local control. For advanced or metastatic disease, systemic therapies are the main intervention and often require molecular profiling of the tumor. Targeted therapy is used if specific genetic alterations are present, such as BRAF mutations, which can be treated with a combination of BRAF and MEK inhibitors. Tumors with KIT mutations may respond to specific tyrosine kinase inhibitors.
Immunotherapy, utilizing drugs known as checkpoint inhibitors, has changed the landscape of melanoma treatment, although its efficacy is more modest in mucosal melanoma compared to cutaneous melanoma. These treatments, which include anti-PD-1 and combination anti-PD-1/anti-CTLA-4 agents, work by helping the patient’s own immune system recognize and attack the cancer cells. The selection of systemic therapy is highly personalized, based on the tumor’s genetic profile and the patient’s overall health.