Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans: What Does It Mean and Why Does It Matter?

Prediction of the biological potential of a tumor is the fundamental goal of the histomorphological, immunohistochemical, and molecular genetic assessment in any sample of human neoplasia. For some tumors, the risk of clinically aggressive behavior is implicit in the classification itself; for other tumors, there are specific attributes, histological or otherwise, that portend a better or worse prognosis. These outcome-associated characteristics often drive key treatment decision making, particularly in an era of therapy that is increasingly accessible, frequently targeted, and generally more efficacious. In the case of dermatofibrosarcoma protuberans (DFSP), potential for aggressive tumor behavior is heralded by what was first observed as a morphological transformation manifesting as a "fibrosarcomatous" appearance: a cellular tumor component arranged in distinctive fascicles exhibiting more conspicuous mitotic activity. In this article, we review the criteria for and clinical implications of diagnosing fibrosarcomatous DFSP. We highlight the potential for histological variation and heterogeneous outcomes, suggesting that fibrosarcomatous DFSP is not a monolithic entity. Finally, we summarize recent advances in our understanding of the molecular correlates of fibrosarcomatous transformation, discuss the diagnostic and treatment-related implications of these advances, and propose future directions for gaining further insight into fibrosarcomatous DFSP, its defining features, and therapeutic vulnerabilities.