Melanocytes in nonlesional sun-exposed skin: A multicenter comparative study

Abstract

There are limited data regarding melanocyte density and distribution on sun-exposed skin of the head and neck, in particular, comparing morphology (hematoxylin-eosin [H&E] staining) and immunohistochemistry (Melan-A staining) on formalin-fixed tissue. Furthermore, comparisons of melanocyte density between distinct geographic populations have not been made using these methods. This information would be useful for physicians who use histologic criteria to diagnose and treat lentigo maligna. We aimed to characterize the density and distribution of melanocytes using Melan-A and H&E stains on nonlesional sun-exposed skin of the face and neck, and compare the results between patients seen in Florida and Minnesota. We also aimed to quantify the presence and extent of features considered characteristic of melanoma in these noncancerous specimens of sun-damaged skin. The overall goal was to be able to provide this information to physicians who perform histopathologic interpretations of skin biopsy specimens to potentially prevent the overdiagnosis of melanoma. In all, 100 patients undergoing Mohs micrographic and reconstructive surgery for basal cell and squamous cell carcinoma were enrolled, 50 each at the two sites. Permanent tissue sections were prepared from sun-exposed skin without clinical lesions. Melanocyte density and distribution were quantified. The overall median and 90th percentile, respectively, of melanocytes per high-power field was 9 and 14 on the H&E-stained sections and 11 and 19 on the Melan-A-stained sections. The means were 9.3 and 12.0, respectively (P < .001). There was evidence that melanocyte densities were higher in patients in Florida than in Minnesota, at least using H&E staining. There was evidence of lower melanocyte densities with increasing age, more so for Melan-A than H&E staining, and higher densities in men using Melan-A. Confluence was noted in 24% of cases using H&E and 45% using Melan-A. More than two thirds of these were classified as having mild confluence, whereas the others demonstrated higher amounts of confluence (3-8 melanocytes). Only 37 patients had a follicle present; of these, 7 patients had follicular extension although this did not extend beyond 1 mm in depth. Cytologic atypia was noted in 19 of the 100 patients; pagetoid spread was found in 3. This was a selected population of patients; results may not be generalizable to the wider population. Variables such as contours of the epidermis (rete density), density of hair follicles, and epidermal thickness may affect the reproducibility of the results. Melanomas were not included for comparison. Relatively high melanocyte density, mild to moderate confluence of melanocytes, focal pagetosis, superficial follicular extension (<1.0 mm), and mild or moderate cytologic atypia may be observed in the absence of a melanocytic neoplasm. It is important for physicians to be aware of these findings so that such features are interpreted appropriately when making a histologic assessment that may ultimately influence therapy and outcome.