Mucosal melanoma is a rare and aggressive form of melanoma, the most dangerous type of skin cancer, that develops on mucosal surfaces in the body. Melanomas are tumours arising from melanocytes which are responsible for producing melanin pigment. This determines the colour of eyes, hair and skin. There are two forms of melanoma: mucosal and cutaneous. Cutaneous arises from the pigment-producing cells on the skin, while mucosal melanoma originates in mucosal tissues which are moist surfaces lining cavities of the body. This includes the mucosal surfaces lining the respiratory tract, gastrointestinal tract, genitourinary tract, and other mucosa-covered surfaces. Here we will explore the symptoms and clinical presentation of mucosal melanoma, highlighting its distinct characteristics, diagnostic challenges, and implications for patient management.

Overview of mucosal melanoma

Melanoma is known for its potential to spread to other body parts early and its resistance to treatment once it has spread. Mucosal melanoma accounts for only about 1-2% of all melanoma cases, making it a rare subset of the disease¹. Despite its rarity, mucosal melanoma is clinically significant due to its aggressive nature and poorer prognosis compared to the other, cutaneous, melanoma. Understanding its symptoms and clinical presentation is crucial for early detection and timely intervention.

Anatomical sites and variations

Mucosal melanoma can arise from various mucosal surfaces in the body. The most common sites are the nasal cavity and paranasal sinuses (the many hollow spaces in the bones around the nose), followed by the oral cavity, anorectal region, vulva, vagina, and urinary tract². Each anatomical site may present with different and distinct symptoms with clinical features discussed below. These influence an individual's diagnostic strategies and treatment decisions made by medical professionals.

Symptoms based on anatomical location

Nasal cavity and paranasal sinuses

Mucosal melanoma in the nasal cavity or paranasal sinuses often presents with nonspecific symptoms initially, such as nasal congestion, epistaxis (nosebleeds), and sinus pain or pressure. Patients may also experience changes in their sense of smell or develop a mass in the nasal cavity visible during physical examination.

Oral cavity

In the oral cavity, mucosal melanoma can manifest as a pigmented lesion on the mucosal surfaces of the lips, gums, tongue, or palate. Symptoms may include persistent oral ulcers, difficulty swallowing (dysphagia), or a lump in the mouth that doesn't heal.

Anorectal region

Mucosal melanoma in the anorectal region often presents with symptoms such as rectal bleeding, changes in bowel habits, pain during defecation, or a palpable mass in the rectum or anus. These symptoms can mimic those of more common benign conditions, leading to diagnostic delays.

Genitourinary tract

In the genitourinary tract, mucosal melanoma can occur in the vulva, vagina, or urinary tract. Symptoms may include vaginal bleeding, vaginal discharge, pain or discomfort in the pelvic area, or visible pigmented lesions on the genital mucosa.

Diagnostic challenges

Diagnosing mucosal melanoma poses significant challenges due to its rarity and the variability in clinical presentation. Many early symptoms mimic benign conditions or more common malignancies, leading to delays in diagnosis. In addition, there are no risk factors associated with the disease. In comparison, cutaneous melanoma is linked with a high sun exposure history which does not relate to mucosal. Moreover, mucosal melanoma can lack the typical features seen in cutaneous melanoma, such as changes in pigmented skin lesions, making it harder to recognize and differentiate.

It is usually diagnosed in the same way as skin melanoma, using a physical examination and a biopsy. During a biopsy, a small piece of the legion is surgically removed and examined under the microscope. Doctors may use a scalpel or razor to take a small section of the suspected cancer. Under the microscope, they are looking for cancerous characteristics. Additional testing will be ordered, such as ultrasounds, blood chemistry or lymph node biopsies, to determine the cancerous stage, providing information about the severity of the disease in the individual. It will also form the basis of the treatment plan to follow. Staging is based on: the thickness of the lesion, ulceration/bleeding at the site, and metastasis of the cancer (spreading).

Clinical evaluation and diagnostic tools

The diagnosis of mucosal melanoma often involves a comprehensive clinical evaluation, including a detailed medical history, physical examination, and imaging studies such as MRI or CT scans. Biopsy and histopathological examination remain the gold standard for definitive diagnosis, where characteristic features of melanoma cells (such as nuclear atypia, prominent nucleoli, and melanin pigment) confirm the diagnosis.

What causes mucosal melanoma?

Researchers aren’t completely confident about what causes mucosal melanoma. They are particularly interested in why melanocytes which protect against sun damage are located in the mucous membranes which hardly see sunlight. They have, however, identified two genetic mutations which may be playing a part in causing the cancer. They are somatic mutations which means they are changes in DNA that happen during your lifetime, you aren’t born with it. These mutated genes occur in a small percentage of mucosal membrane cases:³

• Mutated KIT genes: KIT genes are responsible for how fast certain cells, including melanocytes, grow. They do this by making a protein which drives cell growth. When the KIT genes mutate, the protein signals other proteins to give cells instructions to multiply and divide, faster than normal. Mutated KIT genes have been identified in 7-17% of mucosal melanomas, most common in vulvas (30% cases)
• Mutated BRAF genes: These genes manage proteins that oversee the melanocyte cell population. The proteins rely on BRAF genes for their division instructions. If BRAF genes mutate, the instructions change and they begin to multiply uncontrollably, becoming tumours. These mutated BRAF genes are found in around 3-15% of cases

As these mutations are only detected in less than 20% of diagnoses in each case, it is likely there are other reasons, still undiscovered, causing this cancer.

Prognostic factors and staging

Prognostic factors for mucosal melanoma include the tumour's location, size, depth of invasion, presence of ulceration, and lymph node involvement. Unlike cutaneous melanoma, mucosal melanoma tends to travel around the body (metastasize) early to regional lymph nodes and distant organs, contributing to its poorer prognosis and lower survival rates.

Survival studies show that overall 25% of people with mucosal melanoma were alive 5 years after diagnosis¹. Survival rates vary depending on the region of the melanoma. Vagina and rectum rates are the highest, at 36% of people with this condition alive after 5 years. It is important to remember survival rates are estimates and averages. It may not be true for you. A professional healthcare worker will be able to give you a more calculated estimate, based on your individual circumstances.

Treatment approaches

The management of mucosal melanoma typically involves a multidisciplinary approach, including surgical resection of the primary tumour when feasible. Adjuvant therapies such as radiation therapy and systemic treatments (immunotherapy or targeted therapy) may be considered based on the stage of the disease and individual patient factors. Clinical trials exploring novel treatment modalities are ongoing to improve outcomes for patients with advanced or metastatic disease.

Conclusion

In conclusion, mucosal melanoma presents unique challenges in terms of diagnosis, treatment, and prognosis compared to cutaneous melanoma. Recognizing the symptoms and understanding the clinical presentation based on anatomical location are crucial for early detection and timely intervention. It is hard to diagnose due to its similarity of symptoms compared to much more common, harmless illnesses.  Despite its rarity, mucosal melanoma requires vigilance from healthcare providers to improve patient outcomes through prompt diagnosis and appropriate management strategies.

Understanding the symptoms and clinical presentation of mucosal melanoma is essential for healthcare professionals involved in its diagnosis and treatment. Continued research and awareness efforts are needed to improve early detection, treatment options, and overall survival rates for patients affected by this rare and aggressive form of melanoma.

This article provides a comprehensive overview of the symptoms and clinical presentation of mucosal melanoma, emphasising the importance of early recognition and management in improving patient survival outcomes.