Proliferation and differentiation of the keratinocytes in hyperplastic epidermis overlying dermatofibroma: immunohistochemical characterization.

Epidermal changes overlying dermatofibromas (DFs) have been described as ranging from psoriasiform simple hyperplasia to basaloid hyperplasia sometimes morphologically indistinguishable from superficial basal cell carcinoma (BCC). To characterize epidermal hyperplasia overlying DFs and to determine its association with the disease process, we examined 30 cases of DF showing hyperplastic epidermis. We used nine immunohistochemical markers associated with keratinocyte proliferation or differentiation. In DFs, the dermal metallothionein (MT) expression and immunophenotypic changes with regard to epidermal differentiation varied depending on the stage of lesional evolution of the DFs. Immunostaining for epidermal growth factor receptor (EGFR), MT, and keratin 6 (K6) increased in simple hyperplastic epidermis (SHE) overlying DFs (n = 11), whereas it gradually diminished in basaloid hyperplastic epidermis (BHE) overlying DFs (n = 19). In SHE, there was a significant increase in K14 expression. Among 19 BHE cases, 12 showed premature expression of involucrin and delayed appearance of K1 along with aberrant expression of K14. Conversely, the remaining 7 BHE cases showed a pattern of involucrin and K1 similar to that of normal skin coinciding with decreased or absent dermal MT expression. Loricrin and filaggrin expression in all DFs was the same as that of normal skin. Based on the sparse positivity of Ki-67 in the hyperplastic epidermis overlying DFs, we found that the biologic ability of BHE and SHE was not apparent in the hyperproliferative state observed in psoriasis and BCC. These results suggest that the dermal fibrohistiocytic process may trigger the induction of SHE overlying DFs by an unknown mechanism and then mediate both the abnormal keratinocyte differentiation and the transformation of SHE to BHE through the evolution of the dermal lesions.