Information on the following diseases can be found in the Related Disorders section of this report:

• Basal Cell Carcinoma
• Xeroderma Pigmentosum

Symptoms of atypical mole syndrome usually start during adulthood. The disorder is characterized by the presence of a greater than normal number of moles (often more than 100), unusually large moles (greater than 5 mm in diameter), and moles that are variable in color and may combine more than one color, including tan, brown, black, red and/or pink. These moles have irregular and fuzzy or indistinct borders.

The presence of dust-like melanin (pigments found in the skin), which gives the moles their color, and abnormally large nuclei of skin cells called melanocytes, all visible under the microscope, are characteristic of dysplastic nevus syndrome. The mole-like tumors may spread to adjacent parts of the skin, or through the blood and lymph circulation, to other organs. Certain changes in the melanocyte nuclei indicate when atypical mole syndrome may be changing to malignant melanoma.

Atypical mole syndrome is inherited, but the mode of inheritance is complex and not clearly understood. It is believed to be an autosomal dominant trait in some cases, and it may involve several genes on different chromosomes. Some cases also appear to occur sporadically as the result of random mutations.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Symptoms of atypical mole syndrome usually appear in adulthood. Males and females are affected in equal numbers.

In the United States, the prevalence of this syndrome has been reported as 2-5% of the white population, which is about half the rate reported for Australia and New Zealand. In Sweden, about 18% of white adults are thought to show clinical signs of dysplastic nevus syndrome, but only 8% had confirmed cellular (histological) characteristics of the disorder.

While it is clear that atypical mole syndrome can lead to malignant melanoma, it is not at all clear just what the exact risk is of any single atypical mole changing into a malignant form. The risk rises as the number of moles (nevi) rises. An atypical mole syndrome patient with a family history of malignant melanoma is at greater risk than is a patient without the family history.

The disorder is more common among persons of northern European background than among Afro-Americans or Asians.

Symptoms of the following disorders can be similar to those of atypical mole syndrome. Comparisons may be useful for a differential diagnosis:

Basal cell carcinomas are a common form of skin cancer that may appear as small, shiny, firm nodules; ulcerated, crusted lesions; flat, scar-like hardened plaques; or lesions difficult to differentiate from psoriasis or localized dermatitis.

Xeroderma pigmentosum is a rare autosomal recessive hereditary skin disorder which begins during early childhood. It is characterized by a defect in the ability of certain connective tissue cells (fibroblasts) to repair skin damaged by ultraviolet rays. The skin of people with xeroderma pigmentosum is markedly hypersensitive to sunlight. (For more information, choose "Xeroderma" as your search term in the Rare Disease Data Base.)

Diagnosis
Diagnosis of atypical mole syndrome is reasonably obvious if, on physical examination, an unusually large number of moles are found on the patient’s arms, trunk and/or head. Parts of the body regularly exposed to sunlight are especially vulnerable. The patient’s history will show that some of the moles will be peculiarly colored, or that the color has changed over time. Other moles will have grown in size and/or changed texture.

As soon as possible after one or more moles undergo changes, a biopsy is essential in order to determine if any of the cells that make up the mole have become cancerous.

Treatment
Treatment is primarily a matter of preventive measures, such as staying out of the sun during the hottest time of the day, to lower the risk for malignant melanoma, and of regular self-examination and in-office examination so that any possible malignancies may be detected as early as possible and treated appropriately. It has been well documented that early detection and treatment of malignant melanoma improve the likelihood of successful treatment.

Affected individuals are advised to avoid direct sunlight and use a protective sunscreen. Other preventive measures include wearing a wide-brimmed hat, sunglasses, and protective clothing when in the sun, avoiding tanning machines, and protecting children (and especially infants) from excessive exposure to the sun.

It is not necessary, or even advised, to remove multiple atypical moles beforehand in an attempt to prevent development of malignant melanoma. However, any change in such a mole should be reported to one’s physician immediately.

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 web site.

For information about clinical trials being conducted at the 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

Further information on clinical trials, especially those sponsored by pharmaceutical companies, is available at: www.centerwatch.com

TEXTBOOKS
Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:839.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:989-90.

Champion RH, Burton JL, Ebling FJG, eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992:1543-45.

Habif TP. ed. Clinical Dermatology. 2nd ed. The C.V. Mosby Company. St. Louis, MO; 1990:561-63.

REVIEW ARTICLES
Roesch A, Landthaler M, Vogt T. [The dysplastic nevus. Separate entity, melanoma precursor or diagnostic dilemma? Hautarzt. 2003;54:871-83.

Bauer J, Garbe C. Acquired melanocytic nevi as a risk factor for melanoma development. A comprehensive review of the epidemiological data. Pigment Cell Res. 2003;16:297-306.

Hussein MR, Wood GS. Molecular aspects of melanocytic dysplastic nevi. Recent Results Cancer Res. 2002;160:71-80.

Salopek TG. The dilemma of the dysplastic nevus. Dermatol Clin. 2002;20:617-28.

JOURNAL ARTICLES
Oliveria SA, ChauD, Christos PJ, et al. Diagnostic accuracy in performing skin self-examination and the impact of photography. Arch Dermatol. 2004;140:57-62.

Czajkowski R, Placek W, Drewa G, et al. FAMMM syndrome: pathogenesis and management. Dermatol Surg. 2004;30(2 Pt 2):291-96.

Robinson JK, Nickoloff BJ. Digital epiluminescence microscopy monitoring of high-risk patients. Arch Dermatol. 2004;140:49-56.

Branstrom R, Hedblad MA, Krakau I, et al. Reasons to seek medical attention for a skin check-up: the layman’s perspective. Eur J Public Helath. 2003;13:294-98.

Jamora MJ, Wainwright BD, Meehan SA, et al. Improved identification of potentially dangerous pigmented skin lesions by computerized image analysis. Arch Dermatol. 2003;139:195-98.

Masci P, Borden EC. Malignant melanoma: treatments emerging, but early detection is still key. Cleve Clin J Med. 2002;69:529, 533-34, 536-38.

Zaludek I, Hafmann-Wellenhof R, Cerroni L, et al. White dysplastic melanocytic naevi. Lancet. 2002;359:1999-2000.

Tripp JM, Kopf AW, Marghoob AA, et al. Management of dysplastic nevi: a survey of fellows of the American Academy of Dermatology. J Am Acad Dermatol. 2002;46:674-82.

Salopek TG, Kopf AW, Stefanato CM, et al. Differentiation of atypical moles (dysplastic nevi) from early melanomas by dermoscopy. Dermatol Clin. 2001;19:337-45.

Hussein MR, Sun M, Tuthill RJ, et al. Comprehensive analysis of 112 melanocytic skin lesions demonstrates microsatellite instability in melanomas and dysplastic nevi, but not in benign nevi. J Cutan Pathol. 2001;28:343-50.

FROM THE INTERNET
Dysplastic (Atypical) Nevus. BC Cancer Agency. ©2004. 2pp.
www.bccancer.bc.ca/HPI/CME/SkinCancer/CMESkinCancer/Readings/EarlyDiagnosis/DysplasticNevus.htm

Leavitt SA, Salasche S. Dysplastic Nevi. University of Arizona Health Science Center. nd. 3pp.
www.ahsc.arizona.edu/opa/crnap/nevi.html

Weber PJ. Atypical Mole = Dysplastic Nevus. ©2003. 15pp.
www.skincancerinfo.com/sectionf/atypicalmole.html

The Dermatology Network. Dysplastic Nevi & Malignant Melanoma. nd. 2pp.
www.dermnetwork.org/nevi&melanoma-1.htm

Marghoob AA. The dangers of atypical mole (dysplastic nevus) syndrome. 1999. 11pp
www.postgradmed.com/issues/1999/06_99/marghoob.htm