Critical Analysis of Histologic Criteria for Grading Atypical (Dysplastic) Melanocytic Nevi

Abstract

Low concordance in grading atypical (dysplastic) melanocytic nevi (AMN) has been reported, and no systematic evaluation is available. We studied 123 AMN with architectural and cytologic atypia (40 associated with atypical-mole syndrome), classified according to standard criteria by 3 independent observers. Histologic variables included junctional and dermal symmetry, lateral extension, cohesion and migration of epidermal melanocytes, maturation, regression, nuclear features, nuclear grade, melanin, inflammatory infiltrate location, and fibroplasia. AMN (43 junctional and 80 compound) were graded mild (31), moderate (61), and severe (31). AMN-severe correlated with 3 or more nuclear abnormalities (especially pleomorphism, heterogeneous chromatin, and prominent nucleolus) and absence of regression, mixed junctional pattern, and suprabasilar melanocytes on top of lentiginous hyperplasia. AMN-severe diagnostic accuracy was 99.5% using these criteria, but only the absence of nuclear pleomorphism differentiated AMN-mild from AMN-moderate. No architectural features distinguishing AMN-mild from AMN-moderate were selected as significant by the discriminant analysis. AMN from atypical-mole syndrome revealed subtle architectural differences, but none were statistically significant in the discriminant analysis. Histologic criteria can reliably distinguish AMN-severe but fail to differentiate AMN-mild from AMN-moderate. AMN from atypical-mole syndrome cannot be diagnosed using pathologic criteria alone.

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

“…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.…”

“…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 diagnosis of HG-atypical melanocytic nevi required at least one architectural and two cytological variables, with nuclear pleomorphism being an obligatory criterion. 5 Processing artifacts were found to influence the cohesion of cells in nests (from preserved to diminished), this feature being therefore excluded from the final classification. In case of grading disagreement, the lesions were discussed during simultaneous inspection before final categorization.…”

“…3 Although atypical melanocytic nevi reveal progressive morphological changes, 5 the grading system is controversial and its prognostic relevance is not fully established.…”

Expression of γ-H2AX in melanocytic lesions

“…The diagnostic criteria for melanoma are well established; however, it is sometimes difficult to make a confident distinction between dysplastic nevus and melanoma, as demonstrated by low concordance rates among dermatopathologists [12]. Over the years, many markers, such as Ki-67 (MIB-1), p16, and p53 have been shown to be helpful in differentiating melanoma from nevus [13][14][15].…”