Gastrointestinal Melanoma

Gastrointestinal melanoma is a serious condition where melanoma cancer cells are found in the digestive system, most commonly through spread from skin melanoma, though rare cases begin in the digestive tract itself.

Table of contents

• What is Gastrointestinal Melanoma?
• How Common is This Condition?
• Signs and Symptoms
• How is it Diagnosed?
• Treatment Options
• Outlook and Survival

What is Gastrointestinal Melanoma?

Gastrointestinal melanoma occurs when melanoma (a type of cancer that starts in cells that give skin its color) is found in the digestive tract. The digestive tract includes the stomach, small intestine, large intestine (colon), and rectum.^[1]

Most melanomas found in the gastrointestinal tract are metastases, which means they spread from melanoma that originally developed in the skin or, rarely, in other areas like the eye.^[3] Malignant melanoma is the most common cancer to spread to the gastrointestinal tract.^[1]

In very rare cases, melanoma can start directly in the gastrointestinal tract as a primary gastrointestinal melanoma. This type is extremely uncommon and difficult to diagnose.^[3] Most melanomas found in the stomach are metastases from skin sources rather than starting in the stomach itself.^[3]

• Small bowel (most common site, 35-58% of cases)
• Stomach
• Large intestine (colon)
• Rectum and anus
• Liver

How Common is This Condition?

Malignant melanoma has become the fifth most frequent cancer in the UK.^[1] When melanoma spreads to the gastrointestinal tract, it shows a particular preference for certain areas. The small bowel is the most common site where melanoma spreads in the digestive system, followed by the stomach and large intestine.^[1]

Mucosal melanomas (melanomas that develop in the moist tissues lining body openings) that occur primarily in the gastrointestinal tract are very rare, making up approximately 1% of all melanomas.^[4] Among gastrointestinal mucosal melanomas, anorectal melanomas are the most common and most studied type.^[4]

Melanoma is the most common solid tumor that spreads to the gastrointestinal tract.^[2] An autopsy study of 216 patients with advanced malignant melanoma showed that 22.7% had stomach metastases.^[7]

Signs and Symptoms

The diagnosis of melanoma metastases in the gastrointestinal tract can be difficult because they may not cause any symptoms for some time and may occur years after the initial melanoma diagnosis.^[2] Patients with metastatic melanoma to the gastrointestinal tract can present with nonspecific, generalized symptoms.^[14]

Common symptoms include:

• Abdominal pain
• Nausea and vomiting
• Gastrointestinal bleeding (which may appear as black, tarry stools called melena, or blood in the stool)
• Weight loss
• Fatigue and weakness
• Decreased appetite
• Anemia (low red blood cell count)
• Constipation

In one case, a patient with a history of eye melanoma presented with bleeding from the gastrointestinal tract, fatigue, dizziness, and abdominal pain.^[7] Another case involved a middle-aged man who initially presented with upper gastrointestinal bleeding and had a 9-month history of worsening stomach pain and significant weight loss.^[3]

How is it Diagnosed?

Early diagnosis of gastrointestinal metastases is critical to avoid emergency hospitalizations, and surgical intervention can be curative in some cases.^[2] Excellent diagnostic options are available for identifying gastrointestinal involvement by metastatic melanoma.^[1]

Imaging tests are the primary way to detect gastrointestinal melanoma. CT imaging (a type of scan that uses X-rays and computer technology to create detailed pictures) remains the standard way to stage and monitor melanoma patients, and in most cases, it will be the first imaging test to identify gastrointestinal lesions.^[2] However, interpreting CT studies in patients with melanoma can be challenging because lesions may be subtle and random in location, and sometimes they mimic other conditions.^[2]

Endoscopic procedures allow doctors to look directly inside the digestive tract. These include:

• Upper endoscopy (also called EGD or esophagogastroduodenoscopy) to examine the esophagus, stomach, and upper small intestine
• Colonoscopy to examine the large intestine and rectum
• Video capsule endoscopy, where the patient swallows a small camera that takes pictures as it moves through the digestive tract
• Enteroscopy to examine the small intestine

During these procedures, doctors can take tissue samples called biopsies. The biopsy samples are then examined under a microscope to confirm the diagnosis.^[7] Special staining techniques must be used on the tissue to confirm melanoma. These include immunohistochemistry tests that look for specific proteins found in melanoma cells, such as S-100, HMB-45, MART-1, and Melan A.^[3][7]

It’s important to note that up to 40% of melanoma lesions in the gastrointestinal tract could be amelanotic, meaning they lack the dark pigment typically associated with melanoma, which can make diagnosis even more challenging.^[4]

Treatment Options

Treatment for gastrointestinal melanoma depends on several factors including the extent of disease, the patient’s overall health, and whether the melanoma started in the gastrointestinal tract or spread there from another location.

Surgical treatment plays an important role in managing gastrointestinal melanoma. Complete surgical removal of gastrointestinal metastatic melanoma in carefully selected patients not only provides symptom control but has also been associated with an increase in overall survival.^[1] The role of surgery for patients with metastatic melanoma in the gastrointestinal tract is evolving in the era of effective systemic treatments.^[1]

Surgical removal seeking a negative margin (removing the tumor with a border of healthy tissue around it) is recommended to achieve the best outcome.^[4] Although much of the survival improvement in patients treated for metastatic melanoma is now due to modern drug therapies, surgical removal of oligometastatic disease (typically defined as up to 3 disease sites) remains a key intervention for relieving symptoms and improving survival, even in patients responding to systemic therapy.^[2]

In a large study of 1,105 confirmed cases of primary gastrointestinal melanoma, treatment approaches included chemotherapy (17.3% of patients), radiotherapy (18.3%), both chemotherapy and radiotherapy (5.7%), and surgery alone or combined with chemotherapy and/or radiotherapy (61.9%).^[4] Statistically significant improvement in survival was noted in all treatment strategies that included surgery.^[4]

Systemic therapies have transformed treatment approaches for patients with metastatic melanoma over the past decade. These include:

• Immunotherapy with immune checkpoint inhibitors, which help the body’s immune system recognize and fight cancer cells
• BRAF-targeted therapies and MEK inhibitors for patients whose melanoma has specific genetic mutations

The approval of these therapies has dramatically changed outcomes for patients with advanced melanoma.^[1]

Outlook and Survival

Gastrointestinal mucosal melanomas are usually diagnosed late and have a more aggressive course due to rapid spread through blood vessels and lymph vessels, which leads to poorer outcomes.^[4] The median survival time for melanoma patients presenting with gastrointestinal involvement is less than 1 year.^[7]

Despite gastrointestinal metastases suggesting overall poorer outlook and survival, some patients achieve long-term remission following surgical removal of the tumors.^[2] Early diagnosis and rapid intervention for melanoma in the gastrointestinal tract are important to maximize both length and quality of life.^[2]

There has been significant progress in treating advanced melanoma. Currently, the overall survival of patients with advanced metastatic melanoma who have been treated with a combination of immunotherapy drugs reaches 52% at five years.^[1] The 5-year survival rate of metastatic melanoma has increased from less than 5% in 2010 to around 30% more recently, largely due to earlier diagnosis, surgical intervention, and active drug therapies.^[2]