Malignant Melanoma

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Skin Cancer - Melanoma written for patients

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 body.[1]

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 melanomas.[2]

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See the separate Malignant Melanoma of Skin article.

See the separate Choroidal Melanoma article.

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  • The most common form of melanoma in the central nervous system (CNS) is metastases of cutaneous melanoma. It is rare as a primary malignancy of the CNS and accounts for about 1% of melanomas.
  • 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.[3, 4]
  • 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.
  • Melanomas that metastasise to the CNS are incurable. Treatment is aimed at reducing the size of the tumour by surgery and/or palliative radiotherapy and supportive palliative care.

Mucosal melanoma may particularly present in the anorectum, nasal cavity, genitourinary tract, upper gastrointestinal tract and maxillary sinus.[5]

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 chemotherapy.[6]
  • Melanoma of oral mucosa is very uncommon. Approximately one third of patients have lymph node involvement at presentation.[7] 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 melanomas.[8]

Gastrointestinal melanomas

  • Most gastrointestinal melanomas are metastatic in origin but primary malignant melanomas of the gastrointestinal tract do occur. Malignant melanoma is one of the most common malignancies to metastasise to the gastrointestinal tract. 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 melaena.[9]
  • 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 melanoma.[10]
  • 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 excisions.[11]

Genitourinary melanomas

  • Genitourinary melanoma is rare and classically associated with a poor prognosis.[12]
  • 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 melanoma.[12]
  • Primary melanoma of the female genital system is extremely rare.[13] 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 poor.[14]
  • 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 prognosis.[15]

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.[16]
  • All patients should have a thorough examination of the skin.[16]
  • Occult primary uveal tract melanoma nearly always causes liver metastases before these are apparent at other sites.[16]
  • For patients presenting with inguinal lymphadenopathy, examination of the genital and urinary tracts and anorectum is especially relevant.[16]
  • All patients should be staged with CT scans of the head, chest, abdomen and pelvis.[16]
  • Dabrafenib, vemurafenib is recommended by the National Institute for Health and Care Excellence (NICE) as an option for treating unresectable or metastatic BRAF V600 mutation-positive melanoma.[17, 18]
  • Ipilimumab is recommended as an option for treating advanced (unresectable or metastatic) melanoma in people who have received prior therapy.[19]
  • 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.[20, 21] However, other studies have shown similar five-year survival rates for MUP and MKP.[22]

Further reading & references

  1. Murphy G, Hussey D, Metser U; Non-cutaneous melanoma: is there a role for (18)F-FDG PET-CT? Br J Radiol. 2014 Aug;87(1040):20140324. doi: 10.1259/bjr.20140324. Epub 2014 Jun 5.
  2. Ascierto PA, Kirkwood JM, Grob JJ, et al; The role of BRAF V600 mutation in melanoma. J Transl Med. 2012 Jul 9;10:85. doi: 10.1186/1479-5876-10-85.
  3. Martin-Blondel G, Rousseau A, Boch AL, et al; Primary pineal melanoma with leptomeningeal spreading: case report and review of and review of the literature. Clin Neuropathol. 2009 Sep-Oct;28(5):387-94.
  4. Bookland M, Anderson WS, Biser-Rohrbaugh A, et al; Primary pineal malignant melanoma. Pediatr Neurosurg. 2007;43(4):303-8.
  5. Kim HS, Kim EK, Jun HJ, et al; Noncutaneous malignant melanoma: a prognostic model from a retrospective BMC Cancer. 2010 Apr 28;10:167.
  6. Mendenhall WM, Amdur RJ, Hinerman RW, et al; Head and neck mucosal melanoma. Am J Clin Oncol. 2005 Dec;28(6):626-30.
  7. Patrick RJ, Fenske NA, Messina JL; Primary mucosal melanoma. J Am Acad Dermatol. 2007 May;56(5):828-34. Epub 2007 Mar 8.
  8. Prasad ML, Busam KJ, Patel SG, et al; Clinicopathologic differences in malignant melanoma arising in oral squamous and Arch Pathol Lab Med. 2003 Aug;127(8):997-1002.
  9. Liang KV, Sanderson SO, Nowakowski GS, et al; Metastatic malignant melanoma of the gastrointestinal tract. Mayo Clin Proc. 2006 Apr;81(4):511-6.
  10. Lens M, Bataille V, Krivokapic Z; Melanoma of the small intestine. Lancet Oncol. 2009 May;10(5):516-21.
  11. Meguerditchian AN, Meterissian SH, Dunn KB; Anorectal melanoma: diagnosis and treatment. Dis Colon Rectum. 2011 May;54(5):638-44.
  12. Sanchez-Ortiz R, Huang SF, Tamboli P, et al; Melanoma of the penis, scrotum and male urethra: a 40-year single institution J Urol. 2005 Jun;173(6):1958-65.
  13. Jahnke A, Makovitzky J, Briese V; Primary melanoma of the female genital system: a report of 10 cases and review of Anticancer Res. 2005 May-Jun;25(3A):1567-74.
  14. Sugiyama VE, Chan JK, Kapp DS; Management of melanomas of the female genital tract. Curr Opin Oncol. 2008 Sep;20(5):565-9.
  15. Gupta D, Deavers MT, Silva EG, et al; Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases. Am J Surg Pathol. 2004 Jun;28(6):771-80.
  16. Revised U.K. guidelines for the management of cutaneous melanoma 2010; British Association of Dermatologists
  17. Dabrafenib for treating unresectable or metastatic BRAF V600 mutation‑positive melanoma; NICE Technology Appraisal Guidance, October 2014
  18. Vemurafenib for treating locally advanced or metastatic BRAF V600 mutation‑positive malignant melanoma; NICE Technology Appraisal Guidance, December 2012
  19. Ipilimumab for previously treated advanced (unresectable or metastatic) melanoma; NICE Technology Appraisal Guidance, December 2012
  20. Lee CC, Faries MB, Wanek LA, et al; Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma. J Clin Oncol. 2008 Feb 1;26(4):535-41.
  21. Lee CC, Faries MB, Wanek LA, et al; Improved survival for stage IV melanoma from an unknown primary site. J Clin Oncol. 2009 Jul 20;27(21):3489-95. Epub 2009 May 18.
  22. Katz KA, Jonasch E, Hodi FS, et al; Melanoma of unknown primary: experience at Massachusetts General Hospital and Dana-Farber Cancer Institute. Melanoma Res. 2005 Feb;15(1):77-82.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but makes no warranty as to its accuracy. Consult a doctor or other healthcare professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Colin Tidy
Current Version:
Peer Reviewer:
Dr John Cox
Document ID:
2420 (v23)
Last Checked:
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