Clonal analysis of cutaneous fibrous histiocytoma (dermatofibroma)

Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign fibrohistiocytic lesion involving the dermis and subcutis. Histologically, it is subclassified into fibroblastic and histiocytoid forms. Its histogenesis is controversial. While often referred to as a neoplastic process, definite evidence of neoplasia in DF has been lacking. Alternatively, some authorities have suggested that DF is a fibrosing inflammatory process. Diagnostically, the most important question faced is the distinction from dermatofibrosarcoma protuberans (DFSP). Misdiagnosis can occur, as the early phase of DFSP can simulate DF, particularly the deep and cellular forms of DF.

To address this issue, and to investigate whether DF is in fact a neoplasm, we evaluated 31 examples of DF of various histological types in female patients and assessed clonality by analyzing X-chromosome inactivation as indicated by the methylation status of the androgen receptor gene (HUMARA). Representative cases of DFSP were analyzed for comparison.

Among the selected 31 cases of DF, 24 cases provided intact DNA and informative polymorphism at the AR alleles, including one case of recurrent deep fibrous histiocytoma. Among these 24 cases, randomly inactivated AR alleles were observed in 17 cases including a deep, recurrent fibroblastic DF. A non-random inactivation at AR alleles was observed in seven cases, of which six cases showed either typical histiocytoid form of DF (four cases) or mixed cell types with predominant histiocytoid cell type (two cases). One fibroblastic DF also showed a monoclonal pattern. HUMARA analysis of DFSP revealed non-random inactivation of polymorphic AR alleles.

These findings suggest that DF is a heterogeneous process. Monoclonal genotype was found in DFs with histiocytoid or mixed type with predominant histiocytoid features, suggesting that histiocytoid cells probably represent the neoplastic component. The fibroblastic form of DF may represent a reactive fibroblastic proliferation. Alternatively, it may represent a true neoplasm whose neoplastic cell type has been obscured by prominent reactive fibroblastic component.