Beyond COL1A1::PDGFB: Rare fusions and their clinical implications in dermatofibrosarcoma protuberans

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous intermediate-grade soft tissue tumor characterized by COL1A1::PDGFB fusion in most cases. This fusion drives tumorigenesis and forms the basis for imatinib treatment, which acts by blocking platelet-derived growth factor receptor-beta kinase activity. Apart from this canonical fusion, there is an expanding spectrum of rare fusions, including COL6A3::PDGFD, EMILIN::PDGFD, TNC::PDGFD, etc., through molecular profiling. These atypical rearrangements may be encountered in morphologically classic DFSP, unusual anatomic sites, or diagnostically challenging variants such as fibrosarcomatous DFSP. Their recognition is clinically relevant, as they may influence tumor biology, response to targeted therapy, and eligibility for clinical trials. This newly documented DFSP involving the lacrimal sac was initially misdiagnosed as a solitary fibrous tumor, emphasizing the diagnostic pitfalls in anatomically constrained regions and the importance of integrated diagnosis combining histology, immunohistochemistry, and molecular testing. In this editorial commentary, we briefly highlight the ever-growing genomic landscape of DFSP, report rare fusions and their biological implications, and examine the role of expanded molecular diagnostics in refining diagnosis, guiding therapy, and informing prognosis. Incorporating comprehensive fusion analysis into routine workup may be critical for accurate classification, especially in unusual presentations where reliance on morphology alone risks misdiagnosis.

Keywords: Dermatofibrosarcoma protuberans; COL1A1::PDGFB; EMILIN; TNC; Molecular diagnostics

Core Tip: Apart from canonical COL1A1::PDGFB fusion, dermtofibrosarcoma harbors an expanding spectrum of gene fusions, which include COL1A2::PDGFB, COL6A3::PDGFD, EMILIN2::PDGFD, TNC::PDGFD, FBN1::CSAD, MAP3K7CL::ERG, SLC2A5::BTBD7, and LARGE1::PRKCA, which influence tumor biology, therapeutic response to treatment, and disease prognosis. Since molecular techniques like fluorescence in situ hybridization and polymerase chain reaction can miss these variants, a comprehensive genomic profiling, like next-generation sequencing or ribonucleic acid sequencing, is necessary for correct diagnosis, risk stratification, and eligibility for personalized medicine, particularly in morphologically challenging fibrosarcomatous variants.