Immunophenotype and possible origin of nevi with phenotypical heterogeneity

Biphenotypical nevi or nevi with phenotypical heterogeneity consist of phenotypically different cell populations in a pattern other than that observed in classical combined nevi or in various maturation stages of banal nevocellular nevi. Besides several well-known entities such as deep penetrating nevi and plexiform spindle cell nevi, this category of pigment cell lesions also harbors fewer delineated lesions such as nevi with atypical dermal nodules (N-ADN) and nevi with a focal atypical epithelioid cell component (N-FAECC). Their worrisome histology may result in a wrong diagnosis of malignancy. In order to discriminate them from malignant melanoma and to shed light on their histogenesis, we analyzed the immunophenotypical profile of 33 N-FAECC, 6 N-ADN, and 10 giant congenital nevi removed shortly after birth, using antibodies directed to S100 protein, gp100, tyrosinase, NKI-C3, Melan-A and Mib-1. In N-FAECC and N-ADN, the large polygonal cells expressed gp100, S100 protein and Melan-A, and reacted with monoclonal antibody NKI-C3. In addition, there was intense tyrosinase expression but no Mib-1 immunoreactivity. Unexpectedly, we observed similar single or clustered, large epithelioid cells in three out of ten giant congenital nevi; these cells showed a similar phenotype to those observed in N-ADN and N-FAECC. Our histological and immunohistochemical data suggest that N-FAECC and N-ADN may reflect different stages of the same disorder. Moreover, their resemblance to the large polygonal cells in congenital nevi may suggest that the histogenesis of N-ADN and N-FAECC may be related to the persistence and expansion of large epithelioid cells in congenital nevi shortly after birth.