Grading of Atypia in Nevi: Correlation with Melanoma Risk

Abstract

Nevi with architectural disorder and cytologic atypia of melanocytes (NAD), aka "dysplastic nevi," have varying degrees of histologic abnormalities, which can be considered on a spectrum of grades of atypia. Somewhat controversial and subjective criteria have been developed for grading of NAD into three categories "mild," "moderate," and "severe." Grading involves architectural and cytological features, which often correlate with each other. Architectural criteria were intraepidermal junctional extension beyond any dermal component, complex distortion of rete ridges, and dermal fibrosis. Cytological criteria were based on nuclear size, dispersion of chromatin, prominence of nucleoli, hyperchromasia and variation in nuclear staining. Few tests have been made of the relationship between specific grades of atypia and patient risk for melanoma. Retrospective review of pathology reports was performed on 20,275 nevi examined between 1989 and 1996. From the total, 6,275 were diagnosed as NAD, which were in 4,481 patients. These patients were divided into those whose worst NAD was mild (2,504), moderate (1,657), or severe (320). Review of accession data revealed that a personal history of melanoma was present in 5.7% of patients with mild, 8.1% with moderate, and 19.7% with severe atypia. The male/female ratios were similar in each group. In the three groups, the mean ages of men were similar and of women were similar, but the mean age of men tended to be 6 -11 yrs. older than women in each group. Family histories of melanoma were not considered. The odds ratio as a measure of association between NAD and personal history of melanoma, shows an odds ratio of 4.08 (2.91-5.7) for NAD-severe versus NAD mild, odds ratio 2.81 (2-3.95) for NAD-severe versus NADmoderate and odds ratio 1.45 (1.13-1.87) for NAD moderate versus NAD-mild. These data show that the probability of having personal history of melanoma, for any given NAD patient, correlates with the NAD grade. Likewise, the risk of melanoma is greater for persons who tend to make nevi with high grade histological atypia.

Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi

“…Only the superficial dermal expression of CDKN1A differentiated atypical melanocytic nevi-mild from atypical melanocytic nevi-moderate, suggesting that both lesions cannot be reliably distinguished and would favor to group them as low-grade atypical melanocytic nevi. 5,38 Low-grade atypical melanocytic nevus has a revealed association with histologic regression, suggesting that inflammation regression is unlikely to be secondary to neoplastic progression. 45 The histological regression observed in low-grade atypical melanocytic nevi certainly contributes to the atypical clinical picture and is confirmed by a kinetic profile that suggests a regressive lesion; the potential of neoplastic progression in these atypical melanocytic nevi cannot be predicted on histological grounds only.…”

“…The atypical melanocytic nevus is assumed to represent a malignant melanoma precursor and a marker of increased malignant melanoma risk, 36,37 the risk correlating with the degree of dysplasia. 38,39 The atypical melanocytic nevus grading system is controversial and shows low kappa reproducibility, 40 due to the variable definitions available and the consideration given to moderate dysplasia (either low or high grade). 5,[38][39][40] These definitions tried to reflect the lesion biology, but there are no studies assessing cell kinetics, cell cycle regulators, and cell survival by grade and tumor cell topography.…”

Precursors to melanoma and their mimics: nevi of special sites

“…For patients with severe atypia, the risk of melanoma was almost three-fold greater than for those patients with mild atypia. 7 In the opinion of this author, a pathologist can contribute to the assessment of melanoma risk by identifying histologically dysplastic nevi or nevi with 'dysplastic features'. If these findings are recorded in a pathology report, the clinician should be alerted to assess the risk factors discussed above, and thus to identify individuals whose increased risk for melanoma may warrant lifelong surveillance.…”

“…Using criteria similar to those discussed above, these observers found that the prevalence of a personal history of melanoma was increased in patients with 'nevi with architectural disorder (NAD)' and various grades of histologic atypia (dysplasia). 7 The grading of atypia involved architectural and cytological features, which were often correlated. Architectural criteria included intraepidermal junctional extension beyond any dermal component, complex distortion of rete ridges, and dermal fibrosis.…”

“…[1][2][3][4][5][6][7] Clinically, they are characterized by four major properties ( Figure 1): Their size tends to be greater than that of common nevi but less than that of melanomas; in the most common definition, dysplastic nevi are 5 mm in diameter or greater. Also by definition, dysplastic nevi contain a junctional component, which clinically is macular or flat, sometimes with a 'pebbly' surface.…”