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Atypical Mole (Clark Nevus or Dysplastic Nevus)


Clark nevus (also known as dysplastic nevus) was initially described in melanoma-prone families, implying that it was a premalignant condition.

In 1820, Norris proposed an association between nevi and melanoma. He described a family in which two members developed melanoma, while other members had “many moles on various parts of their bodies.”

In 1974, Munro
described an association of lesions and a family history of melanoma. These nevi had the clinical and microscopic appearance of what are now called atypical moles. In 1978 and 1981, Clark et al
described these lesions as dysplastic nevi when they were observed in a series of family members of whom 36% had melanomas. The dysplastic nevi were characterized clinically by showing variability in size, border, and colors. Histologically, they described mesenchymal changes in the papillary dermis with a lymphocytic infiltrate. Clark described these families as having a “B-K mole syndrome.”
Also during 1981, Elder introduced the phrase “dysplastic nevus syndrome” (DNS), describing the presentation of sporadic dysplastic nevi. He divided dysplastic nevi into those showing epithelioid and lentiginous cell dysplasia. He defined cytological features found in dysplastic nevi, including nuclear pleomorphism, hyperchromatism, dusty cytoplasm, prominent nucleoli, and hyperchromasia.
Similarly during this time, Lynch et al described a similar nevus phenotype in a melanoma-prone family, coining the phrase, “familial atypical multiple-mole melanoma (FAMMM) syndrome.”

In 1984, Clark introduced five histological criteria for the characterization of a dysplastic nevus. The following features were included in the proposed criteria

Lentiginous melanocytic hyperplasia

Melanocytic nuclear atypia

Lamellar fibroplasia

Concentric eosinophilic fibroplasia

Patchy lymphocytic infiltrates

Also in 1984, Reed introduced the concept of grading the dysplasia as mild, moderate, or severe.
In the late 1980s, Mihm et al expanded Reed’s concept by describing criteria for the three different grades of dysplasia based on nuclear size, chromatin changes, and cytoplasmic attributes.
During the 1980s, Ackerman extensively debated the concept of dysplastic nevi and challenged the hypothesis of this being a precursor to melanoma, emphasizing architectural changes over nuclear atypia for the assessment of melanocytic lesions.

Numerous definitions and criteria have been proposed, including the use of the term atypical moles for clinically suspicious nevi and Clark nevi for those that histologically present with the architectural changes described by Clark. Unfortunately, when clinically abnormal nevi are evaluated histologically, some studies have shown a lack of concordance, with some clinically abnormal nevi having no dysplastic features and some normal-appearing nevi having features of Clark nevi.

The terms atypical mole and Clark nevus continue to be used interchangeably, regardless of clinical or histologic appearance. Modern molecular methods, including genetic markers, cytokines, proliferation indexes, and cyclins, are all undergoing study to help determine which atypical moles may progress to melanoma, although no single marker has been determined.

Atypical moles differ from common acquired melanocytic nevi in several respects, including diameter and lack of pigment uniformity. Confusion exists because some atypical moles cannot be clinically distinguished from melanoma. The clinical and histologic appearances of atypical moles occurring in a familial setting appear to overlap with sporadically occurring atypical moles.

The US National Institutes of Health Consensus Conference on the diagnosis and treatment of early melanoma recommended “dysplastic nevus” be replaced with “atypical nevus” and that histologically, lesions be diagnosed as “nevi with architectural disorder with a statement as to the presence and degree of melanocytic atypia.” The panel also created criteria for FAMMM syndrome, which are as follows

The occurrence of malignant melanoma in one or more first- or second-degree relative

The presence of numerous (often >50) melanocytic nevi, some of which are clinically atypical

Many of the associated nevi showing certain histologic features (see Histologic Findings)

See the images below.

Atypical nevus. The central portion of this mole i

Atypical nevus. The central portion of this mole is a complex papule. The periphery of the lesion is macular, indistinct, slightly pink. Courtesy of the National Cancer Institute, via Wikimedia Commons.

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Atypical nevus. The delicate, hazy, tan, macular r

Atypical nevus. The delicate, hazy, tan, macular rim of this lesion, although not clinically dramatic, represents persistent melanocytic proliferation beyond the lateral limits of the common mole at its center. Courtesy of the National Cancer Institute, via Wikimedia Commons.

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This mole has a characteristic “fried-egg” appeara

This mole has a characteristic “fried-egg” appearance. The eccentric papule is an ordinary nevus. The diagnostic histologic features are found in the macular portion of the mole, particularly at the shoulder (ie, where the papule meets the macule). Courtesy of the National Cancer Institute, via Wikimedia Commons.

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See Mole or Melanoma? Test Yourself With These Suspicious Lesions, a Critical Images slideshow, to help identify various skin lesions.

For additional information on malignant melanoma, see Malignant Melanoma. Additionally, the Medscape Skin Cancer Resource Center and Melanoma Resource Center may be helpful.

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