Dermatofibrosarcoma protuberans: From molecular pathogenesis to multimodal management

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a borderline malignant, locally highly aggressive, but rarely metastasizing fibroblastic skin tumor. This review aims to provide a comprehensive, evidence-based overview of DFSP, encompassing its molecular pathogenesis, diagnostic workup, clinical variants, and current treatment strategies. Its diagnosis is based on histology, immunohistochemistry and molecular detection of PDGFB rearrangements. Wide excision with complete margin control or micrographic surgery is recommended as standard surgical treatment of DFSP. Radiotherapy and PDGFR-directed tyrosine kinase inhibitors, particularly imatinib, are employed for locally advanced, inoperable, or metastasized DFSP. For DFSP with fibrosarcomatous transformation (DFSP-FS), treatment analogous to high-grade soft tissue sarcomas — including wide resection, presentation at a sarcoma center, and potentially systemic therapy — is required. In contrast, for classical DFSP after R0 resection, a conservative follow-up concept is sufficient. This review summarizes current data on epidemiology, prognosis, and clinical variants (including Bednar tumor and giant cell fibroblastoma) and emphasizes the prognostic relevance of DFSP-FS. By integrating current molecular, histopathological, and clinical evidence, this review seeks to support clinicians in optimizing individualized, risk-adapted management of DFSP across all disease stages.