Comprehensive histopathological comparison of epidermotropic/dermal metastatic melanoma and primary nodular melanoma

Metastatic melanoma involving the epidermis and/or upper dermis may show significant histological overlap with primary cutaneous melanoma, especially the nodular subtype. Proper histopathological classification is crucial to appropriate staging and management, but is often challenging. The aim of this study was to identify helpful histopathological features for differentiating epidermotropic/dermal metastatic melanoma (EDMM) and primary nodular melanoma (PNM).

A cohort of EDMMs (n = 74) and PNMs (n = 75) was retrospectively reviewed for various histopathological features, and the data were compared between groups by the use of univariate analysis. Features significantly associated with EDMM included a tumour size of <2 mm, an absence of tumour-infiltrating lymphocytes and plasma cells, monomorphism, and involvement of adnexal epithelium. Features associated with PNM included a polypoid (exophytic) configuration, prominent tumour-infiltrating plasma cells (TIPs), a tumour size of >10 mm, ulceration, epidermal collarettes, a higher mitotic rate, necrosis, multiple phenotypes, significant pleomorphism, and lichenoid inflammation. In multivariate analysis, a logistic regression model including large tumour size, ulceration, prominent TIPs, lichenoid inflammation and epidermal collarettes was highly predictive of PNM. Six (8%) EDMMs from three patients showed an 'epidermal-only' or 'epidermal-predominant' pattern closely simulating in-situ or microinvasive melanoma. Two of these cases were tested by fluorescence in-situ hybridisation, which confirmed clonal relationships with their corresponding primary melanomas.

This is the first comprehensive histopathological comparison of EDMM and PNM. Recognition of the above histopathological associations should aid in the correct classification and staging of cutaneous melanoma. Epidermotropic metastatic melanomas may occasionally show an epidermal-only/epidermal-predominant pattern; accurate diagnosis requires prudent clinical correlation and, when necessary, ancillary molecular tests.