Dysplastic Nevi

Introduction

Dysplastic nevi (DN) are a common clinical entity encountered by dermatologists, and have been the source of significant controversy since their initial description over 30 years ago. The clinical relevance of these lesions lies in their well-recognized contribution to an increased risk for melanoma. Studies have demonstrated that DN are reported in up to 34–56% of melanoma cases, and their presence may confer up to a 10-fold increase in melanoma risk.

The biologic nature of DN has yet to be fully elucidated. In the sequential progression model for melanocytic tumors proposed by Clark over 30 years ago, DN represent a point on a continuum that spans from the benign nevus at one end to melanoma at the other. Based on this principle, it has been contended by some that DN are obligate precursor lesions to melanoma. It was at one time proposed that DN and melanoma were pleiotropic effects of a single gene. Genetic studies have since confirmed that this is not the case. Others have refuted the term ‘dysplastic nevus’, stating that all nevi are abnormal, and what Clark referred to as dysplastic nevi are stable, benign lesions that represent the most common melanocytic nevus in man which do not advance along a stepwise neoplastic progression, but instead are characterized by indolence and regression.

DN remain a highly debated issue and controversial subject in dermatology. While there is controversy regarding the malignant potential of DN, the lesions themselves are benign and there is agreement that they serve as a phenotypic discriminator of those individuals at increased risk for melanoma. As such, recognition of DN is important in the management of patients at risk for melanoma.

History

The first reported observation of the dysplastic nevus dates back to 1820 when William Norris described melanoma as a familial syndrome associated with large numbers of moles. In 1952, Edward P. Cawley and colleagues similarly described a family with several cases of cutaneous melanoma and increased numbers of nevi. It was not until 1978, however, that the clinicopathological entity now known as the dysplastic nevus was formally described. W.H. Clark and colleagues examined 58 patients affected by familial melanoma along with spousal controls, and characterized the pigmented lesions in these patients with a distinct set of clinical and histological features. They defined a new disease entity, the B-K mole syndrome, named after two of the patients that contributed to their study. In 1983, Lynch et al. described a family exhibiting a similar phenotype that displayed concordance for malignant melanoma. They termed this syndrome familial atypical multiple mole melanoma (FAMMM) syndrome and noted an inheritance pattern consistent with a simple autosomal dominant factor. In 1980, Elder et al. described 79 melanoma cases that occurred in a non-familial context in patients with multiple abnormal moles, recognizing a sporadic pattern of expression of the phenotype.

Various other names have been applied to the dysplastic nevus, including Clark's nevus and atypical mole, and significant controversy has ensued over the naming of these lesions both clinically and histologically. Due to the lack of a common definition and disagreement over appropriate diagnostic criteria, the National Institutes of Health held a consensus conference in 1992 in order to clarify both the validity and significance of DN, as well as to make recommendations regarding the diagnosis and treatment of DN and early melanoma. It was concluded that the dysplastic nevus is a clinicopathologic entity that the represents an acquired pigmented tumor whose clinical and histologic appearance is different from common moles. The recommendation was to discontinue use of the term ‘dysplastic’ due to the diversity of its intended meaning by different investigators. Instead, the panel suggested that these lesions be refered to as ‘atypical moles’, and that histologically they be described as ‘nevi with architectural disorder’, along with a statement describing the presence and degree of melanocytic cytologic atypia. The committee also proposed that the phenotype observed in members of melanoma-prone families consisting of large numbers of DN be called familial atypical mole and melanoma (FAM-M) syndrome, and that these individuals be screened closely for melanoma. However, this terminology was never fully accepted by the medical community. Over the past 25 years, the term dysplastic nevus has been the most frequently used by clinicians, pathologists and researchers.