Atypical Mole (Dysplastic Nevus) Syndrome

Familial melanoma and melanoma precursors.
Cutaneous melanoma may occur as isolated, so-called sporadic cases; in association with multiple atypical nevi; or in familial clusters, in which case it is referred to as the atypical-mole syndrome (AMS), formerly known as dysplastic nevus syndrome. In the late 1970s, the dysplastic nevus (DN) or atypical mole (AM) was identified in melanoma-prone families. It was then determined that AMs are cutaneous markers that identify specific family members who are at increased risk for melanoma. The AM may also be the single most important precursor lesion of melanoma. These nevi may occur in persons from melanoma-prone families and in persons who lack both a family history and a personal history of melanoma.

Atypical-mole syndrome and familial melanoma.
Numerous families with multiple melanoma patients have been reported. These patients usually develop melanoma at a young age, have a predisposition to multiple primary melanomas, and have the tendency to develop thin, superficial-spreading melanomas. Large, unusual-looking moles were initially recognized as a precursor to melanoma in patients with familial cutaneous melanoma. This syndrome was named B-K mole syndrome from two of the probands, and the precursor nevi were designated as B-K moles and later referred to as dysplastic nevi. The syndrome is now called the atypical-mole syndrome. Recent estimates suggest that approximately 32,000 persons in the United States have familial atypical-mole syndrome with familial melanoma, accounting for approximately 5.5% of all melanomas diagnosed. Hereditary malignant melanoma and atypical moles represent pleiotropic effects of a mendelian autosomal dominant gene with high penetrance.
One study showed that the hereditary cutaneous malignant melanoma/atypical-mole syndrome does not predispose to other cancers.

Definition.
The National Institutes of Health (NIH) Consensus Conference on Diagnosis and Treatment of Early Melanoma has defined the familial atypical mole and melanoma syndrome as (1) the occurrence of malignant melanoma in one or more first- or second-degree relatives; (2) a large number of melanocytic nevi (MN), often more than 50, some of which are atypical and often variable in size; and (3) melanocytic nevi that demonstrate certain histologic features. AMS probably represents a spectrum. At one end all members of a kindred have AMs and some have malignant melanoma (MM). At the other end are persons with one AM without a personal and/or family history of MM.

Association with melanoma.
Patients with AMS, familial or sporadic, are at significant risk for developing melanoma. Atypical moles have been observed in 8% of patients with nonfamilial (sporadic) melanoma, and the transformation into superficial-spreading melanoma has been photographically documented. Family members without atypical moles do not show any apparent increase in melanoma risk. The frequency of sporadic AMs in the general population is unknown.
Atypical moles are found on the skin of 90% of patients with hereditary melanomas, and more than 50% of melanomas in this group are associated histologically with and probably evolve from atypical moles. The lifetime risk of developing cutaneous melanoma among the white population in the United States is approximately 0.8%, or 1 in 125. Persons who have AMs and no family members with the disease have a 6% risk of developing melanoma. Persons who have AMs and a history of melanoma have a 10% risk of getting a second melanoma; persons who have AMs and have a family member with melanoma have a 15% risk. The lifetime risk of melanoma approaches 100% for those people with AMs from families with two or more first-degree relatives who have cutaneous melanoma.
Among atypical-mole-bearing family members, those patients with melanoma have very large numbers of nevi more frequently than patients with AMs without melanoma. Family members with AMs have more nevi than do patients who have only common acquired nevi.

Clinical features of atypical moles

Morphology.
These unusual nevi differ in a number of important ways from typical acquired pigmented nevi or moles. Atypical moles are larger than common moles. They have a mixture of colors, including tan, brown, pink, and black. The border is irregular and indistinct and often fades into the surrounding skin. The surface is complex and variable, with both macular and papular components. A characteristic presentation is a pigmented papule surrounded by a macular collar of pigmentation ("fried-egg lesion"). In one study, the total number of nevi and macular components were the only useful features to predict histologic melanocytic dysplasia. However, "fried-egg lesions" often do not display histologic melanocytic dysplasia. In contrast, the absence of a macular component in melanocytic nevi in a person with fewer than 13 total body nevi accurately predicts the absence of melanocytic dysplasia on histologic examination.

Development and distribution.
Atypical moles are not present at birth, but begin to appear in the mid-childhood years as typical common moles. The appearance changes at puberty, and newer lesions continue to appear well after the age of 40. Common moles occur most often on sun-exposed areas. AMs occur in those locations and at unusual sites such as the scalp, buttocks, and breast. The predilection sites for melanoma in familial AMS patients of both sexes correspond with the distribution of nevi; in males nevi and melanoma counts are higher on the back, in females both the back and the lower extremities are affected. These findings strongly suggest an association between nevus distribution and melanoma occurrence and site in familial AMS.

Histology.
The NIH Consensus Conference listed the histologic criteria as follows: architectural disorder with asymmetry, subepidermal (concentric eosinophilic and/or lamellar) fibroplasia, and lentiginous melanocytic hyperplasia with spindle or epithelioid melanocytes aggregating in nests of variable size and forming bridges between
adjacent rete ridges. Melanocytic atypia may be present to a variable degree. In addition, there may be dermal infiltration with lymphocytes, as well as the "shoulder" phenomenon (intraepidermal melanocytes extending singly or in nests beyond the main dermal component).