Atypical Melanocytic Nevi: Grading and Classification of Dysplasia and Dermatoscopic Findings

The tumor progression in melanocytic lesions is assumed to follow a multistep process where the genetic alterations and the morphological steps are closely related. In general terms, this process is usually identified pathologically as dysplasia, intraepithelial malignancy, and early neoplasm. However, melanocytic lesions with dysplasia are, on one hand, controversial in its diagnostic criteria and, on the other hand, difficult to grade and subcategorize due to its heterogeneity. The key condition is the atypical (dysplastic) melanocytic nevus (AMN), which requires both architectural and cytological features to be defined and always needs grading to provide a more accurate risk assessment for the development of malignant melanoma. At this point, it is essential to identify reliably and predict high-grade dysplasia/melanoma-in-situ (HGD-MIS) at clinical, dermatoscopic, biological, and pathological levels within these highly heterogeneous lesions.
AMN-HGD and MIS share the same clinical and dermatoscopic features, which makes extremely hard to differentiate between them at this level. They are clearly different from atypical nevi with low-grade dysplasia, which usually present with soft clinical and dermatoscopic findings. Key dermatoscopic features for the low-grade vs. high-grade distinction are atypical pigment network, eccentric hyperpigmented blotches, and peripheral globules. Histologically, HGD-MIS is mainly defined by junctional asymmetry with both lentiginous and nested patterns, suprabasal melanocytes and at least three nuclear abnormalities (mainly nuclear enlargement, anisokaryosis and hyperchromatism as more predictive features). Biologically, these lesions reveal both cell kinetics and topographic genetic heterogeneity, which are mostly driven by abnormal TP53, dissociated from cyclin-dependent kinase inhibitors (p21WAF1-CDKN1A and p27KIP1-CDKN1B), especially for MIS. The differential diagnosis requires distinguishing them from atypical but not dysplastic melanocytic lesions (particularly in specific locations), and invasive malignant melanomas (mostly thin and non-tumorigenic status). The implications are also different for lentiginous and epithelioid dysplastic lesions, whose criteria are weighted in a slightly different way. Finally, the progression pathway in dysplastic melanocytic lesions is unlikely linear at morphological and genetic levels, and they show a distinct correlation with the molecular subtypes of malignant melanomas.