Dermatofibrosarcoma Protuberans (DFSP): Diagnostics and Molecular Pathology

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing soft tissue sarcoma of the skin (STS), accounting for around 1–1.8% of all STS cases [ 1 , 2 ]. DFSP predominantly affects young to middle-aged adults and shows a slight male predominance with a higher incidence reported among Black individuals [ 1 , 3 ]. This slow-growing mesenchymal skin tumour typically presents as indurated plaque, nodule, or multinodular cutaneous mass [ 4 ]. The term “protuberant” in its name refers to the lumps of tissue that form under the skin. Clinically, DFSP can vary from plaques or small nodular lesions to large, irregular masses. It is a locally aggressive tumour with a tendency for local recurence, but rarely metastasises, occurring in approximately 1–4% of cases (often less than 5%) [ 5 ]. Although rare, metastasis is more likely to occur in certain circumstances. For example, it is more likely to occur if the tumour is large or located in specific areas, such as the head and neck [ 6 ]. Classic DFSP has a favourable prognosis, with a five-year progression-free survival (PFS) rate of around 93% [ 7 ]. However, the prognosis is significantly worse for fibrosarcomatous transformation (FS), a high-grade variant, with a 5-year PFS rate of just 33% and a 14.4–57% risk of metastasis; (median 6.8 years), 5-year OS was 64% (median time for OS was not reached) [ 7 , 8 ]. LR occurs in up to 58% of FS-DFSP cases, and though it is uncommon in classic DFSP, distant metastasis becomes a notable concern with FS change [ 7 ]. Surgical excision remains the cornerstone of treatment. Mohs micrographic surgery (MMS) offers the lowest LR rates thanks to complete margin evaluation. Studies have shown that the recurrence rate for MMS is significantly lower (around 1–2%) than for wide local excision (WLE; 7–30%) [ 1 , 9 , 10 , 11 ]. Yet, WLE with margins of 2–3 cm is an acceptable alternative [ 12 ]. For locally advanced or unresectable disease, imatinib, a tyrosine kinase inhibitor that targets the COL1A1-PDGFB fusion gene, is an effective treatment, particularly in cases where the genetic mutation has been confirmed. Objective response rates are over 50% as was shown by our clinic [ 7 , 13 , 14 ]. Therefore, a correct diagnosis is essential as FS differentiation affects both prognosis and the therapeutic strategy. To guide the use of targeted therapies like imatinib, molecular confirmation via FISH or RT-PCR for COL1A1-PDGFB fusion is recommended as stated in multiple guidelines including ESMO and NCCN [ 12 , 15 , 16 , 17 , 18 ].