55 Kenosia Avenue
Danbury, CT 06810
Phone: 203.744.0100
Toll Free: 1.800.999.6673
http://rarediseases.org

Melanoma, Malignant

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1989, 1990, 1992, 1995, 1996, 1997, 1998, 1999, 2000, 2002, 2003, 2004

Synonyms of Melanoma, Malignant

Disorder Subdivisions

General Discussion

Malignant Melanoma is a common skin cancer that arises from the melanin cells within the upper layer of the skin (epidermis) or from similar cells that may be found in moles (nevi). This type of skin cancer may send down roots into deeper layers of the skin. Some of these microscopic roots may spread (metastasize) causing new tumor growths in vital organs of the body.

Symptoms

In the early stages, most melanomas do not produce any specific symptoms. Later they may appear as lesions that do not heal or an existing mole that shows changes in size or color. A physician should be consulted when any lesion, pigmented or not, becomes itchy, burns, softens or hardens, forms a scab, bleeds, becomes surrounded by a reddened or inflamed area, changes color, size, or shape.

Disorder Subdivisions:
Acral Lentiginious melanoma is a malignant skin cancer that occurs in areas that are not excessively exposed to sunlight and where hair follicles are absent.

Juvenile Melanoma is a benign, elevated, pink to purplish-red papule, with a slightly scaly surface. It usually appears on the face, especially the cheeks. This type of melanoma most often occurs before puberty and may be mistaken for malignant melanoma.

Malignant Lentigo (Melanoma) is a precancerous area on the skin that resembles a freckle. It may be brown or black in color and irregular in shape; it usually occurs on the face. This type of Melanoma occurs most often in older people.

Causes

The exact cause of Malignant Melanoma is unknown. Excessive exposure to the sun, particularly before puberty, and living in areas that are closer to the sun (i.e., tropical climates), increases the risk of developing skin cancer.

A defective gene known as CDK4 has been identified and may be associated with an increased risk for familial Malignant Melanoma. Approximately ten percent of people with Malignant Melanoma may have the familial form of the disease. This familial tendency may be transmitted through autosomal dominant genes. A genetic predisposition to an illness means that some people may carry the defective gene but never get the disorder unless something in the environment triggers the disease

Human traits including the classic genetic diseases are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Malignant Melanoma affects males and females in equal numbers. The incidence of these types of skin cancers is increasing at a relatively fast rate as compared with other forms of cancer. The risk of melanoma is higher in people of European descent than in other populations. A darker pigmentation to the skin may be associated with a lower risk of Malignant Melanoma. It is also associated with a greater risk for those individuals with blue eyes and a fair complexion.

In 1995, approximately 34,000 Americans were diagnosed with Malignant Melanoma; it is thought to affect approximately 40,300 Americans every year. In addition, each year in the US and Canada, between 1,680 and 2, 240 individuals are diagnosed with ocular melanoma.

Related Disorders

Symptoms of the following disorders can be similar to those of Malignant Melanoma. Comparisons may be useful for a differential diagnosis:

Basal Cell Carcinoma is a common skin cancer. It may appear as small, shiny, firm nodules; ulcerated, crusted lesions; or flat, scar-like hardened patches that may bleed. Without a biopsy, this type of skin cancer is difficult to differentiate from psoriasis or localized dermatitis.

Squamous Cell Carcinomas usually appear on sun-exposed areas of the skin, but may occur anywhere on the body. The lesions begin as small red elevations or patches with a scaly or crusted surface. They may become nodular, sometimes with a warty surface. In some patients, the bulk of the lesion may lie below the level of the surrounding tissue. A biopsy is essential to diagnose this disorder.

Kaposi's Sarcoma (KS) may appear as small, tan-to-purple pigmented papules, plaques, nodules, tumors, or ulcers. This type of skin cancer may infiltrate the body, involving the oropharynx and gastrointestinal tract, disseminating to other organs such as the liver, lung, and bone. Chemotherapy has been helpful in treating Kaposi's Sarcoma. Up until the last decade, KS was reported mostly in older men of Ashkenazi Jewish or Mediterranean descent and those with a compromised immune system. The more recent increased incidence of Kaposi's Sarcoma is due to AIDS (Acquired Immunodeficiency Syndrome); about 30% of those with AIDS will also be diagnosed with Kaposi's Sarcoma.

Standard Therapies

The treatment for malignant melanoma depends on the level, stage, and location of the skin cancer at the time of diagnosis. For stage 1 disease, surgery to remove the affected area involves a wide excision with 5 cm margins around the lesion. In some locations, such as the face, smaller margins must be accepted. In Stage 2 disease, the cancer has progressed to the lymph nodes; additional surgery then involves complete removal of the involved nodes (lymphadenectomy). Regular follow-ups are advisable and typically include an annual chest x-ray.

For individuals with metastatic disease, certain chemotherapeutic agents (drugs) are being used alone or in combination with other drugs. Decarbazine, used in this manner has resulted in a temporary remission for some patients. A course of treatment that includes high-dose alkylating agents, such as cyclophosphamide, cisplatin, and carmustine, may also be effective as a treatment for malignant melanoma.

The FDA has approved the use of the orphan drug Aldesleukin (Proleukin) for metastatic melanoma. The drug is made by:
The Chiron Corporation
4560 Horton Street
Emeryville, CA 94608

The drug Intron A (alpha-interferon) has been recommended for approval for the treatment of people with malignant melanoma who have also had surgery (adjuvant therapy). Intron A is manufactured by Schering-Plough.

Researchers from Yale University recently proposed new guidelines for follow-up of individuals with melanoma. Based upon the potential for recurrences, researchers recommend the following surveillance schedule for the detection of recurrences:

Stage 1 - annually.
Stage 2 - every six months for the first two years and annually thereafter.
Stage 3 - every three months for the first year, every four months for the second year, every six months for years 3 to 5, and annually for year six and beyond.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website. In the spring of 2004, there were more than 90 clinical trials and studies examining malignant melanoma listed on this web site. A majority of these studies were focused on the condition in its more advanced, often metastatic, stages.

For information about clinical trials being conducted at the National Institute of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Information on cancer clinical trials is also available through the Internet on www.cancer.gov or by telephone at (800) 4-CANCER.

The FDA granted orphan status to the drug thymalfasin (Zadaxin) in March 2006 to treat stage IIb through stage IV malignant melanoma. This followed a phase II clinical trial that concluded in 2005. Plans to initiate a phase III trial are currently being drawn up. The drug's manufacturer, SciClone Pharmaceuticals, and that company's European development partner, Sigma-Tau, will sponsor the trial.

Antigenics, Inc., is recruiting approximately 230 patients for an international clinical trial to study the efficacy and safety of Oncophage therapy for Stage IV melanoma. Patients are enrolled into one of two treatment arms: conventional treatment (surgery and/or immunotherapy and/or chemotherapy) or Oncophage. Patients who receive Oncophage therapy undergo surgery to remove all or part of the tumor. A portion of this tissue is sent to the Antigenics laboratory, where tumor-derived vaccines are made. Patients who enroll in the study have a 67 percent chance of receiving treatment with Oncophage. Oncophage injections are given on an outpatient basis to minimize disruption of the patient's everyday life. For additional information, contact an Antigenics Research Study staff member at (866) 805-8993 or send e-mail to clinicalaffairs@antigenics.com.

At the present time, there are several drug studies investigating possible new treatments for malignant melanoma. Researchers are trying to develop drugs to enhance the immune system, including a vaccine. Autologous bone marrow transplants are being preformed experimentally for treatment of malignant melanoma. More research must be conducted to determine long-term safety and effectiveness of these drugs and procedures.

In August 2000, Genasense, an anticancer compound produced by the Genta Corporation, was granted orphan drug status by the U.S. Food and Drug Administration (FDA). The drug is currently in clinical trials. Genasense blocks cells from producing a certain protein called BCL2, which is a factor in a variety of cancers. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of malignant melanoma.

The U.S. Food and Drug Administration has granted orphan drug status to histamine dihydrochloride (Maxamine) for use as an adjunct to cytokine therapy for treatment of metastatic malignant melanoma. The drug is produced by Maxim Pharmaceuticals.

Clinical trials are underway to study Interleukin-2 and Tumor-Infiltrating Lymphocytes in individuals with melanoma.

Several clinical trials are underway to study the use of therapeutic vaccines for the treatment of metastatic melanoma. The studies are evaluating the safety and possible therapeutic roles of various preparations of the melanoma tumor-antigen peptide vaccines.

The drug beta alethine (Betathine) has received an orphan drug designation for its use in the treatment of metastatic melanoma. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of metastatic melanoma. For more information, contact:

Dovetail Technologies, Inc.
10615 Mantz Rd
Silver Spring, MD 20903

A new gene therapy, gp 100 adenoviral, has received an orphan drug designation for its use in the treatment of metastatic melanoma. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of metastatic melanoma. For more information, contact:

Genzyme Molecular Oncology
15 Pleasant Street Connector
Framingham, MA 01701
Tel: (508) 271-2627
Fax: (508) 271-2604
E-mail: sage@genzyme.com

A new gene therapy, MART-1 adenoviral, has received an orphan drug designation for its use in the treatment of metastatic melanoma. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of metastatic melanoma. For more information, contact:

Genzyme Corporation
One Kendall Square
Cambridge, MA 02139

Researchers have recently determined that, in rare cases, some individuals with malignant melanoma have a natural immune system reaction that prevents the skin cancer from recurring. The immune systems of such individuals develop an antibody against a substance (gm2) that is found on the surface of melanoma cells. The antibodies hunt down gm2 and destroy the host cells (melanoma cells). Researchers hope to develop a method to stimulate the immune systems of affected individuals (whose immune systems do not react to gm2) against gm2. More study and research is needed to determine the long-term safety and effectiveness of any such method.

Researchers are studying the use of a nonviral two-gene combination therapy using an IL-2 cytokine gene and a SEB superantigen gene as a treatment for melanoma. More studies are needed to determine the long-term safety and effectiveness of this treatment for melanoma.

Researchers are studying the use of isolation limb perfusion as a treatment for melanoma. More studies are needed to determine the long-term safety and effectiveness of this treatment for melanoma.

The drug Interferon, used alone or in combination with other chemotherapeutic agents, is being tested as a treatment for melanoma. One study found the long-term use of low doses of interferon alpha-2a as a treatment of melanoma is safe and beneficial. More studies are needed to determine the long-term safety and effectiveness of this treatment.

The drug temozolomide (Temodal) has received an orphan drug designation from the Food and Drug Administration (FDA) as a treatment for advanced metastatic melanoma. A recent Phase III study of temozolomide versus dacarbazine for treatment of individuals with advanced metastatic malignant melanoma demonstrated that temozolomide was equally effective. Further studies are needed to determine the long-term safety and effectiveness of temozolomide as a treatment for individuals with advanced metastatic melanoma.

The drug pegylated arginine deiminase (Melanocid) has received an orphan drug designation for its use in the treatment of malignant melanoma. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of malignant melanoma. For more information, contact:

Phoenix Pharmacologics, Inc.
115 John Robert Thomas Dr.
Exton, PA 19341

The drug Allovectin-7, which helps the immune system recognize and attack cancer cells, has received an orphan drug designation for the treatment of invasive and metastatic melanoma. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of melanoma. The product is manufactured by Vical, Inc.

Melanoma, Malignant Resources

Organizations:

References

TEXTBOOKS
Berkow R, Beers M. Eds. The Merck Manual. 17th ed. Merck Research Laboratories, Whitehorse Station, NJ; 1999:843-45.

Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:993-94.

JOURNAL ARTICLES
Middleton MR, et al., Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18:158.

Poo-Hwu WJ, et al., Follow-up recommendations for patients with American Joint Committee on Cancer Stages I-III malignant melanoma. Cancer. 1999;86:2252-8.

Pecherstorfer M, et al., Cutaneous melanoma metastases. New Eng J Med. 1998;338:922-3.

Clurman BE, et al., The CDKN2A tumor-suppressor locus - a tale of two proteins. New Eng J Med. 1998;338:910-2.

Monzon J, et al., CDKN2A mutations in multiple primary melanomas. New Eng J Med. 1998;338:879-7.

Grobb JJ, et al., Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5mm without clinically detectable node metastases. French cooperative group on melanomas. Lancet. 1998;351:1905-0.

Marzolini C, et al., Pharmacokinetics of temozolomide in association with fotemustine in malignant melaoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration. Cancer Chemother Pharmacol. 1998;42:433-40.

Brock Cs, Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res. 1998;58:4363-7.

Dhodapkar M, et al., Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Clin Cancer Res. 1997;3:1093-100.

Pecherstorfer M, et al., Cutaneous melanoma metastases. New Eng J Med. 1998;338:922-3.

Clurman BE, et al., The CDKN2A tumor-suppressor locus - a tale of two proteins. New Eng J Med. 1998;338:910-2.

Monzon J, et al., CDKN2A mutations in multiple primary melanomas. New Eng J Med. 1998;338:879-7.

Grobb JJ, et al., Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5mm without clinically detectable node metastases. French cooperative group on melanomas. Lancet. 1998;351:1905-0.

Marzolini C, et al., Pharmacokinetics of temozolomide in association with fotemustine in malignant melaoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration. Cancer Chemother Pharmacol. 1998;42:433-40.

Brock Cs, Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res. 1998;58:4363-7.

Dhodapkar M, et al., Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Clin Cancer Res. 1997;3:1093-100.

Shea TC, et al., Malignant melanoma. Treatment with high dose combination alkylating agent chemotherapy and autologous bone marrow support. Arch Dermatol. 1988;124:878-4.

Shea TC, et al., Malignant melanoma. Treatment with high dose combination alkylating agent chemotherapy and autologous bone marrow support. Arch Dermatol. 1988;124:878-4.

FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 155600: Last Edit Date; 11/1/2002: Entry Number; 155601: Last Edit Date; 5/8/2001.

Report last updated: 2008/04/20 00:00:00 GMT+0