Diagnosis of DFSP as well as genetics, differential diagnosis and the mechanism of imatinib

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Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade mesenchymal neoplasm that arises in the dermis and subcutaneous tissue. Clinically, DFSP presents as a slow-growing cutaneous plaque or nodular mass that is often initially mistaken for a benign dermatological condition, such as a keloid, a dermatofibroma or morphea. Due to its local aggressiveness and proclivity for subclinical spread and recurrence, accurate diagnosis and complete surgical excision are critical. Although DFSP rarely metastasises, its morbidity primarily stems from locally invasive growth and potential disfigurement due to extensive resections. The pathognomonic COL1A1-PDGFB fusion, which can be detected using fluorescence in situ hybridisation (FISH) or reverse transcription polymerase chain reaction (RT-PCR), sustains autocrine PDGFRβ activation and can be used as a diagnostic marker and a target for the drug imatinib. Emerging genomic studies have revealed additional fusions, such as COL1A2-PDGFB and FBN1-CSAD, as well as mutations, such as CDKN2A/B deletions, that correlate with more aggressive, fibrosarcomatous (FS) variant. We reviewed the diagnostics of DFSP, including histopathology, immunohistochemistry (e.g. CD34, factor XIIIa, S100 and PRAME) as well as clinical presentation and recommended imaging modalities (e.g. ultrasound, MRI and PET/CT). To provide a better understanding of DFSP we discussed the molecular basis of DFSP, including the main genetic drivers and downstream signalling pathways, such as Ras-MAPK, PI3K-Akt and FGFR. Moreover, as there is no definitive staging system for DFSP, we proposed a novel one, integrating the presence of FS differentiation.

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