WILLIAMSBURG, VA. Although large numbers of neviespecially dysplastic neviare clearly associated with an increased melanoma risk, the lesions themselves do not appear to become cancerous, Dr. Terry L. Barrett said at the annual meeting of the American Society for Mohs Surgery.
"I remain unconvinced that either the common acquired nevus or the dysplastic nevus develops into melanoma," said Dr. Barrett, professor of pathology and dermatology at the University of Texas, Dallas. "I think they are both benign lesions the majority of the time. Usually, melanomas in these patients arise on normal-appearing skin and not the site of the nevus. When that happens, I think it's coincidental, not a nevus gone bad."
Few studies have actually investigated this point, although Dr. Barrett did mention a 2007 in vitro study that looked at levels of polycomb group protein EZH2, a cell regulatory protein markedly elevated in malignant skin lesions (J. Cutan. Pathol. 2007;34:597-600). The level in both in situ and invasive melanoma was almost three times that seen in acquired and dysplastic nevia finding that seems to support Dr. Barrett's opinion.
Regardless of the source, however, patients with large numbers of nevi are at a significantly increased risk of melanoma and other malignancies. The two commonly recognized nevi syndromes carry different risks, Dr. Barrett said.
Familial atypical mole/melanoma syndrome is an autosomal dominant disorder that increases the lifetime risk of melanoma by almost 100%. Sporadic dysplastic nevus syndrome is a spontaneous mutation that increases the relative risk of malignancy up to 46 times that of the general population, he said.
For patients with the sporadic syndrome, sun exposure seems to play a key role in the development of melanoma. "It's been suggested that intermittent sun exposure manifests the phenotype of the dysplastic nevi [and its attendant increased melanoma risk], while patients without sun exposure manifest the common acquired nevi," Dr. Barrett noted.
"There is no clear agreement among dermatologists about how these lesions should be handled," he said. "If you think a lesion is premalignant, you'll want to excise it, and if the report comes back 'severely atypical,' you'll probably want to have negative margins. If you think the lesions aren't premalignant, then after you exclude a diagnosis of melanoma, you probably won't do anything. We have people in our practice who do both."
The phase in which a dermatologist "catches" the nevus probably influences treatment decisions. "These lesions are dynamic, change throughout life, and can be acquired at any age. I think what's happening is that if we biopsy them in a quiescent phase, we don't see cytological atypia. And if we catch them in a dynamic phase, they have different cellular characteristics, which we then have to define as mild or severe atypia," Dr. Barrett said.
Since the lesions are so changeable, and patients are at such a significantly increased risk of melanoma, close follow-up at 3- to 11-month intervals is crucial. It's probably a good idea to screen first-degree relatives, too, he suggested.