View source for Melanoma

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{{Infobox_Disease |
  Name           = Melanoma |
  Image          = Melanoma malignum.jpg|
  Caption        = Melanoma malignum on the left leg of a 60-year-old woman |
  Width          = 225 |
  DiseasesDB     = 7947 |
  ICD10          = {{ICD10|C|43||c|43}} |
  ICD9           = {{ICD9|172}} |
  ICDO           = {{ICDO|8720|3}} |
  OMIM           = 155600 |
  MedlinePlus    = 000850 |
  eMedicineSubj  = derm |
  eMedicineTopic = 257 |
}}
{{CMG}}
{{Editor Join}}
{{Melanoma}}
==[[Melanoma overview|Overview]]==

==[[Melanoma historical perspective|History]]==

==Epidemiology==

The incidence of melanoma has increased in the recent years, but it is not clear to what extent changes in behavior, in the environment, or in early detection are involved.<ref>{{cite journal | author = Berwick M, Wiggins C | title = The current epidemiology of cutaneous malignant melanoma. | journal = Front Biosci | volume = 11 | issue = | pages = 1244-54 | year = | id = PMID 16368510}}</ref>

==[[Melanoma causes|Causes]]==

==[[Melanoma risk factors|Risk factors]]==

==[[Melanoma pathophysiology|Pathophysiology]]==

== Diagnosis == 

:[[Melanoma history and symptoms| History and Symptoms]] | [[Melanoma physical examination | Physical Examination]] | [[Melanoma staging | Staging]] | [[Melanoma laboratory tests | Lab Tests]] | [[Melanoma electrocardiogram|Electrocardiogram]] | [[Melanoma x ray|X Ray]] |  [[Melanoma MRI|MRI]] | [[Melanoma CT|CT]] | [[Melanoma echocardiography|Echocardiography]] | [[Melanoma other imaging findings|Other imaging findings]] | [[Melanoma other diagnostic studies|Other diagnostic studies]]

==Treatment==
Treatment of advanced malignant melanoma is performed from a multidisciplinary approach including [[Dermatology|dermatologists]], medical [[oncologists]], radiation oncologists, surgical oncologists, general surgeons, [[plastic surgery|plastic surgeons]], [[neurologists]], [[neurosurgeons]], [[otorhinolaryngologists]], [[radiologists]], [[pathologists]]/dermatopathologists, research scientists, [[nurse practitioner]]s and [[physician assistant]]s, and [[palliative care]] experts.  Nurse practitioners (NPs) and physician assistants (PAs) are qualified to evaluate and treat patients on behalf of their supervising physicians. Treatment guidelines can be found through many resources available to health care professionals around the world.  Inspired by melanoma’s increasing prevalence, researchers are seeking to understand the pathways that regulate [[melanin]] production.

[[Melanoma medical therapy|Medical therapy]] | [[Melanoma surgery|Surgical options]] | [[Melanoma primary prevention|Primary prevention]]  | [[Melanoma secondary prevention|Secondary prevention]] | [[Melanoma cost-effectiveness of therapy|Financial costs]] | [[Melanoma future or investigational therapies|Future therapies]]



===Adjuvant treatment===
High risk melanomas may require referral to a medical or surgical oncologist for adjuvant treatment. In the United States most patients in otherwise good health will begin up to a year of high-dose [[interferon]] treatment, which has severe side effects, but may improve the patients' prognosis.<ref>{{cite journal | author = Kirkwood J, Strawderman M, Ernstoff M, Smith T, Borden E, Blum R | title = Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. | journal = J Clin Oncol | volume = 14 | issue = 1 | pages = 7-17 | year = 1996 | id = PMID 8558223}}</ref> This claim is not supported by all research at this time and in Europe interferon is usually not used outside the scope of clinical trials.<ref>{{cite journal | author = Kirkwood J, Ibrahim J, Sondak V, Richards J, Flaherty L, Ernstoff M, Smith T, Rao U, Steele M, Blum R | title = High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. | journal = J Clin Oncol | volume = 18 | issue = 12 | pages = 2444-58 | year = 2000 | id = PMID 10856105}}</ref><ref>{{cite journal | author = Kirkwood J, Ibrahim J, Sondak V, Ernstoff M, Ross M | title = Interferon alfa-2a for melanoma metastases. | journal = Lancet | volume = 359 | issue = 9310 | pages = 978-9 | year = 2002 | id = PMID 11918944}}</ref> 

Metastatic melanomas can be detected by X-rays, CT scans, MRIs, PET and PET/CTs, ultrasound, LDH testing and photoacoustic detection.<ref>{{cite journal | author =  Weight RM, Viator JA, Dale PS, Caldwell CW, Lisle AE. | title = Photoacoustic detection of metastatic melanoma cells in the human circulatory system. | journal = Opt Lett.| volume = 31 | issue = 20 | pages = 2998-3000 | year = 2006 | id = PMID 17001379}}</ref>  

====Chemotherapy and immunotherapy====
Various [[chemotherapy]] agents are used, including [[dacarbazine]] (also termed DTIC), [[Cancer immunotherapy|immunotherapy]] (with [[interleukin-2]] (IL-2) or [[interferon]] (IFN)) as well as local perfusion are used by different centers. They can occasionally show dramatic success, but the overall success in metastatic melanoma is quite limited.<ref>{{cite journal | author = Bajetta E, Del Vecchio M, Bernard-Marty C, Vitali M, Buzzoni R, Rixe O, Nova P, Aglione S, Taillibert S, Khayat D | title = Metastatic melanoma: chemotherapy. | journal = Semin Oncol | volume = 29 | issue = 5 | pages = 427-45 | year = 2002 | id = PMID 12407508}}</ref> IL-2 (Proleukin®) is the first new therapy approved for the treatment of metastatic melanoma in 20 years. Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in this disease, although only in a small percentage of patients.<ref>{{cite journal | author = Buzaid A | title = Management of metastatic cutaneous melanoma. | journal = Oncology (Williston Park) | volume = 18 | issue = 11 | pages = 1443-50; discussion 1457-9 | year = 2004 | id = PMID 15609471}}</ref> A number of new agents and novel approaches are under evaluation and show
promise.<ref>{{cite journal | author = Danson S, Lorigan P | title = Improving outcomes in advanced malignant melanoma: update on systemic therapy. | journal = Drugs | volume = 65 | issue = 6 | pages = 733-43 | year = 2005 | id = PMID 15819587}}</ref>

===Lentigo maligna treatment===
Some superficial melanomas (lentigo maligna) have resolved with an experimental treatment,  [[imiquimod]] (Aldara®) topical cream, an immune enhancing agent.  Application of this cream has been shown to decrease tumor size prior to surgery, reducing the invasiveness of the procedure.  This treatment is used especially for smaller melanoma in situ lesions located in cosmetically sensitive regions.  Several published studies demonstrate a 70% cure rate with this topical treatment.  With lentigo maligna, surgical cure rates are no higher. Some dermasurgeons are combining the 2 methods: surgically excise the cancer, then treat the area with Aldara® cream post-operatively for 3 months.

===Radiation and other therapies===
[[Radiation therapy]] is often used after surgical resection for patients with locally or regionally advanced melanoma or for patients with unresectable distant metastases. It may reduce the rate of local recurrence but does not prolong survival.<ref>{{cite journal | author = Bastiaannet E, Beukema J, Hoekstra H | title = Radiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications. | journal = Cancer Treat Rev | volume = 31 | issue = 1 | pages = 18-26 | year = 2005 | id = PMID 15707701}}</ref>

In research setting other therapies, such as [[gene therapy]], may be tested.<ref>{{cite journal | author = Sotomayor M, Yu H, Antonia S, Sotomayor E, Pardoll D | title = Advances in gene therapy for malignant melanoma. | journal = Cancer Control | volume = 9 | issue = 1 | pages = 39-48 | year = | id = PMID 11907465}}''[https://www.moffitt.usf.edu/pubs/ccj/v9n1/pdf/39.pdf Full text (PDF)]''</ref> [[Radioimmunotherapy]] of metastatic melanoma is currently under investigation. 
<p>Experimental treatment developed at the National Cancer Institute (NCI), part of the National Institutes of Health in the US was used in advanced (metastatic) melanoma with moderate success.
The treatment, adoptive transfer of genetically altered autologous lymphocytes, 
depends on delivering genes that encode so called T cell receptors (TCRs), into patient's lymphocytes. After that manipulation lymphocytes recognize and bind to certain molecules found on the surface of melanoma cells and kill them.<ref name="nih">[http://www.nih.gov/news/pr/aug2006/nci-31b.htm Press release from the NIH]</ref>

==Equine melanoma==
Melanomas are also not uncommon in horses, being largely confined to grey (or white) animals - 80% of such pale horses will develop melanomata by 15 years of age<ref name=CeCO>Centre for Comparitive Oncology [http://www.vetmed.vt.edu/ceco/melanoma.html], accessed at 2220 on 12th July</ref>; of these, 66% are slow growing but all may be classified as malignant<ref name=CeCO/>. [[Surgical]] excision may be attempted in some cases, if the tumours are limited in extent and number. However, they are often multiple (especially in older animals) and [[perineal]] tumours are notoriously difficult to excise. Often, a position of "benign neglect" is assumed, especially if the tumours are not causing any [[clinical]] problems. [[Medical]] therapy with [[cimetidine]] (2.5-4.0mg/kg three times daily for 2 months or more)<ref>Warnick, LD, Graham, ME, and Valentine, BA (1995) "Evaluation of cimetidine treatment for melanomas in seven horses" ''Equine Practice'', 17(7): 16-22, 1995</ref> is also an option, although it has a lower success rate than [[surgery]] and [[cryosurgery]]<ref> RJ Rose & DR Hodson, ''Manual of Equine Practice'' (p. 498) 2000</ref>.

==Future thought==
<p>One important pathway in [[melanin]] synthesis involves the transcription factor [[MITF]].  The MITF gene is highly conserved and is found in people, mice, birds, and even fish.  MITF production is regulated via a fairly straightforward pathway.  [[UV radiation]] causes increased expression of transcription factor [[p53]] in [[keratinocytes]], and p53 causes these cells to produce melanoctye stimulating hormone ([[MSH]]), which binds to [[MC1R]] receptors on [[melanocytes]].  Ligand-binding at MC1R receptors activates [[adenyl cyclases]], which produce [[cAMP]], which activates [[CREB]], which promotes [[MITF]] expression.  The targets of MITF include [[p16]] (a CDK inhibitor) and [[Bcl2]], a gene essential to [[melanocyte]] survival.  It is often difficult to design drugs that interfere with transcription factors, but perhaps new drugs will be discovered that can impede some reaction in the pathway upstream of MITF. 
<p>Studies of [[chromatin]] structure also promise to shed light on transcriptional regulation in melanoma cells.  It has long been assumed that [[nucleosomes]] are positioned randomly on [[DNA]], but murine studies of genes involved in melanin production now suggest that nucleosomes are stereotypically positioned on DNA.   When a gene is undergoing transcription, its transcription start site is almost always nucleosome-free.  When the gene is silent, however, nucleosomes often block the transcriptional start site, suggesting the nucleosome position may play a role in gene regulation.     
<p>Finally, given the fact that tanning helps protect skin cells from UV-induced damage, new melanoma prevention strategies could involve attempts to induce tanning in individuals who would otherwise get sunburns.  Redheads, for example, do not tan because they have MC1R mutations.  In mice, it has been shown that the melanin-production pathway can be rescued downstream of MC1R.   Perhaps such a strategy will eventually be used to protect humans from melanoma.

==References==
{{Reflist|2}}

==External links==
===Websites===
*[http://www.mmmp.org Melanoma Molecular Map Project]
*[http://www.proleukin.com Proleukin]
*[http://www.melanomaperspectives.com Melanoma Perspectives]
*[http://www.skincancer.org/melanoma/index.php Information on Melanoma from The Skin Cancer Foundation]
* [http://www.cimit.org/ CIMIT Center for Integration of Medicine and Innovative Technology - New Advances and Research in Melanoma]
* [http://www.newsmonster.co.uk/sunlight-prevents-and-cures-cancer-and-a-healthy-tan-makes-you-look-good.html Sunbathing helps prevent cancer: UK newspaper article]
* [http://www.melanomainternational.org/ Melanoma International Foundation]
* [http://www.skincheck.org/ Melanoma Education Foundation]
* [http://www.melanoma.com/ melanoma.com] (commercially supported site)
* [http://www.dermnetnz.org/lesions/melanoma.html DermNet NZ: Melanoma]
* [http://www.startoncology.net/capitoli/interno_capitoli/default.jsp?menu=professional&ID=32&language=eng Professional melanoma information]
* [http://www.rah.sa.gov.au/cancer/melanoma/ Adelaide Melanoma Unit] (free information on diagnosis, prevention, treatment of melanoma; booklet available at cost)
*[http://copublications.greenfacts.org/en/sunbeds/index.htm Assessing health risks of sunbeds and UV exposure] summary by GreenFacts of the European Commission SCCP assessment

===Patient information===
* [http://www.cancer.gov/pdf/WYNTK/WYNTK_moles.pdf What You Need To Know About Moles and Dysplastic Nevi] - patient information booklet from cancer.gov (PDF)
* [http://www.mpip.org/ MPIP: Melanoma patients information page]
* [http://www.MelanomaSupport.org.au/ Melanoma Support Organisation (Victoria, Australia)] - Ran by Melanoma Sufferers with strong links to Cancer Institutes in Victoria, Australia
* [http://www.melanomapatients.org/ Melanoma Patients Australia]
* [http://www.tustison.com/interests1.shtml/ Mikes Page - The Melanoma Resource Center]
* [http://listserv.icors.org/SCRIPTS/WA-ICORS.EXE?SUBED1=mel-l&A=1/ MEL-L - Melanoma e-mail list for patients, caregivers and healthcare professionals] - Supporting the Melanoma Patient since 1996

===Images, photographs===
*[http://www.dermnet.com/thumbnailIndex.cfm?moduleID=14&moduleGroupID=427&groupIndex=0&numcols=0 Melanoma photo library at Dermnet]
* [http://dermatlas.med.jhmi.edu/derm/result.cfm?Diagnosis=53 DermAtlas: Melanoma images]
* [http://www.lumen.luc.edu/lumen/MedEd/medicine/dermatology/melton/melcont.htm Photographs of melanoma]
* [http://melanoma.blogsome.com/ Skin imaging methods for melanoma diagnosis](commercial advertising)
* [http://dermatologie.free.fr/cas21b.htm Pictures of melanomas]
* [http://dermatologie.free.fr/cas183re.htm Pictures of amelanotic melanomas]

===Videos===
* [http://www.healthination.com/skin_cancer.php Health Video: Melanoma and Non-Melanoma Skin Cancers - Overview, Prevention, and Treatment]
* [http://www.healthination.com/skin_self_exam.php Health Video: How to Perform a Skin Self Exam]


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[[Category:Dermatology|Melanoma]]
[[Category:Types of cancer|Melanoma]]
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