Molecular Pathogenesis and Histological Variability of Dermatofibrosarcoma Protuberans

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a kind of infrequent tumor of the soft tissues distinguished by its gradual proliferation and a preference for regional reoccurrence, despite its limited capacity for metastasis. At the molecular level, a significant majority of DFSP cases manifest the t (17;22) (q22; q13) chromosomal translocation, resulting in the fusion of the collagen type I alpha chain (COL1A1) gene and platelet-derived growth factor B chain (PDGFB) gene. This fusion results in PDGFB overexpression, consequently activating the PDGF Receptor-beta (PDGFR-β). The activated PDGFR-β serves as a central nexus for numerous intracellular signaling pathways, initiating cascades including Phosphatidylinositol 3-kinase (PI3K)/Akt, Mitogen-Activated Protein Kinase (MAPK)/extracellular signal-regulated kinase (ERK), and STATs pathways. These cascades collectively enhance DFSP cell growth, proliferation, and invasiveness. Histologically, DFSP tumors are predominantly fibroblastic and display distinct immune cell infiltration patterns in their microenvironment. Elevated expression of CD4+ naïve cells, CD4+ Th2 cells, CD8+ central memory T cells, B cells, and macrophages is evident, while levels of CD4+ central memory T cells and eosinophils are diminished. Immunohistochemical analyses further highlight that most DFSP cells exhibit positive cytoplasmic CD34 expression, whereas factor XIIIa and α-smooth muscle actin are notably absent. Clinically, DFSP presents in diverse subtypes, each characterized by its unique histological profile. Prominent subtypes encompass classic DFSP, fibrosarcomatous DFSP (FS-DFSP), pigmented DFSP, giant cell fibroblastoma, myxoid DFSP, atrophic DFSP, and the granular cell variant. This review aspires to deliver an exhaustive insight into DFSP, accentuating its molecular underpinnings and clinical presentation, with the ultimate goal of advancing our understanding and management of this distinct dermatological entity.