Malignant melanoma

What is malignant melanoma?

Cancerous growth of melanocytes results in melanoma. The vast majority of melanomas are from the skin but malignant melanomas have been described in nearly every organ of the body¹ . Non-cutaneous melanomas are rare² .

BRAF is a serine/threonine protein kinase activating the MAP kinase/ERK-signalling pathway. It is encoded on chromosome 7q34. About 50% of melanomas have activating BRAF mutations. BRAF V600 has been implicated in different mechanisms underlying the development of melanomas³ .

Malignant melanoma of skin

See the separate Malignant Melanoma of Skin article.

Choroidal melanoma

See the separate Choroidal Melanoma article.

Melanoma of the central nervous system

• The most common form of melanoma in the central nervous system (CNS) is metastases of cutaneous melanoma. Melanoma has the highest risk of spread to the CNS among all common cancer types. It is rare as a primary malignancy of the CNS⁴ .

• Primary intracranial melanoma can arise from the leptomeninges or dura mater.

• Primary melanomas of the pineal region (see the separate Pineal Tumours article) are very rare and may be difficult to diagnose^{5 6} .

• Spread to the meninges gives a worse prognosis.

• Neurocutaneous melanoma is a congenital disorder in infants with giant hairy melanocytic naevi. The leptomeningeal tissues are invaded, involving the brain or spinal cord. Severe neurological compromise or death results.

Mucosal melanoma

Mucosal melanoma may particularly present in the anorectum, nasal cavity, genitourinary tract, upper gastrointestinal tract and maxillary sinus⁷ .

Head and neck

See the separate Head and Neck Cancers article.

• Primary mucosal melanoma of the head and neck is rare and is associated with a poor outcome.

• Standard therapy is surgical resection, possibly associated with adjuvant radiation and chemotherapy⁸ .

• Melanoma of oral mucosa is very uncommon. Approximately one third of patients have lymph node involvement at presentation⁹ . The outlook is poor with a five-year survival of 10-25% and a median survival of less than two years.

• Sinonasal melanomas have a similar prognosis to oral melanomas¹⁰ .

Gastrointestinal melanomas

• Most gastrointestinal melanomas are metastatic in origin but primary malignant melanomas of the gastrointestinal tract do occur. Malignant melanoma is the most common carcinoma to metastasise to the gastrointestinal tract¹¹ .

• Metastases to the gastrointestinal tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, haematemesis and melaena¹² .

• Small intestine melanomas can be primary tumours or metastases from cutaneous, ocular or anal melanomas. Primary intestinal melanoma is extremely rare, whereas metastatic melanoma of the small bowel is common because of the tendency for cutaneous melanoma to metastasise to the gastrointestinal tract. Patients with primary melanoma of the small intestine have a worse prognosis than that of patients with metastases of cutaneous melanoma¹³ .

• Anorectal melanoma (see also the separate Anal Carcinoma article) is uncommon with a median survival of less than 20 months. Abdominoperineal resection has historically been the treatment of choice but there has been a shift toward less-mutilating wide local excisions¹⁴ .
  

Genitourinary melanomas

• Genitourinary melanoma is rare and classically associated with a poor prognosis¹⁵ .

• Partial penectomy or wide local excision provides effective local control for low-stage penile or urethral melanomas and all scrotal lesions. Prophylactic modified inguinal lymphadenectomy should be considered in patients with penile, scrotal and anterior urethral melanoma¹⁵ .

• Primary melanoma of the female genital system is extremely rare¹⁶ . Surgery remains the initial treatment of choice for localised melanomas of the female genital tract, with less radical, organ function-preserving resections. Radiotherapy may play a role in the treatment of patients with close resection margins, regional nodal metastasis or unresectable tumours. The results of treatment for female genital tract melanomas are poor¹⁷ .

• Melanoma involving the ovary is rare and predominantly seen in women of reproductive age. The tumour is most often metastatic from another site and is unilateral in most cases. Melanoma of the ovary is associated with a poor prognosis¹⁸ .

Melanoma of unknown primary site

See also the separate Malignancy of Unknown Origin article.

• No primary lesion is identified in 10-20% of patients presenting with palpable evidence of regional metastatic melanoma. Metastatic melanoma with an unknown primary site may be found in lymph nodes only.

• Patients with occult primary melanoma may present with a solitary metastasis, lymph node disease or systemic disease.

• All patients should have a thorough examination of the skin.

• Occult primary uveal tract melanoma nearly always causes liver metastases before these are apparent at other sites.

• For patients presenting with inguinal lymphadenopathy, examination of the genital and urinary tracts and anorectum is especially relevant.

• All patients should be staged with CT scans of the head, chest, abdomen and pelvis.

• Immunotherapy and targeted therapy with BRAF inhibitors and/or inhibitors of mitogen-activated extracellular signal-regulated kinase (MEK inhibitors) have significantly improved the overall survival of patients with melanoma of unknown primary¹⁹ .

• Dabrafenib is recommended by the National Institute for Health and Care Excellence (NICE) as an option for treating unresectable or metastatic BRAF V600 mutation-positive melanoma²⁰

• Vemurafenib is recommended as an option for treating BRAF V600 mutation-positive unresectable or metastatic melanoma²¹ .

• Ipilimumab is recommended as an option for treating advanced (unresectable or metastatic) melanoma in people who have received prior therapy²² .

• Some studies have found a significantly better postoperative survival for melanoma of unknown primary (MUP) versus melanoma of known primary (MKP), suggesting a strong endogenous immune response against the primary melanoma^{23 24} . However, other studies have shown similar five-year survival rates for MUP and MKP²⁵ .