Sclerotic Epithelioid Dermatofibroma With Cytokeratin Expression

BACKGROUND: Dermatofibromas are common benign dermal lesions with numerous histological variants. The combination of sclerotic and epithelioid features is extremely rare, with very few cases documented in the literature. CASE REPORT: We describe a 64-year-old male with a history of rheumatoid arthritis treated with methotrexate who presented with an asymptomatic 1-cm erythematous plaque on the chest. Histopathological examination revealed a symmetrical intradermal lesion composed of epithelioid cells with prominent nucleoli, dispersed between thick, hyalinized collagen bundles. No epidermal connection or cytological atypia was identified. Immunohistochemical analysis showed a unique profile: the neoplastic cells were positive for factor XIIIa, CD68, and vimentin, but also demonstrated strong, aberrant expression of cytokeratins (AE1/AE3, CK8/18) and the epithelial markers p40 and p63. Markers for muscle, vascular, melanocytic, and neural differentiation were negative. CONCLUSION: This is the first reported case of sclerosing epithelioid dermatofibroma exhibiting diffuse cytokeratin and p40/p63 expression. Recognizing this atypical immunophenotype is crucial to avoid diagnostic pitfalls, as it may mimic malignant epithelial or mesenchymal neoplasms such as sarcomatoid squamous cell carcinoma or epithelioid sarcoma. The expression likely reflects phenotypic plasticity rather than true epithelial malignancy.