Abstract
Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma in which complete surgical excision is standard treatment, although some tumors are initially unresectable. Neoadjuvant imatinib has been proposed in these cases, but data on its histopathological and molecular effects and long-term outcomes remain limited. To evaluate the clinical, histopathological and molecular impacts of neoadjuvant imatinib prior to modified Mohs surgery (MMS) in locally advanced DFSP. Single-center, retrospective study. After a mean of 10 months of neoadjuvant imatinib, partial tumor size reduction was observed in 60% of patients (mean reduction 37.8%), while the remaining cases showed disease stabilization; no complete responses were recorded. All tumors exhibited marked volumetric and consistency reduction, with histology revealing extensive hypocellular hyaline regression and attenuated CD34 and nestin expression. Persistence of COL1A1-PDGFB fusion transcripts was detected in post-treatment samples. Following MMS, local recurrence occurred in 30% of patients at long-term after a mean of 10.8-year follow-up since the last surgery. Neoadjuvant imatinib in locally advanced DFSP results in tumor volume reduction without decreasing the final surgical defect. The histological response is typically patchy and may compromise detection of residual disease, potentially increasing the risk of local recurrence.