Identification of a novel SH3PXD2B::FER fusion in a case of plexiform myofibroblastic tumor and review of the literature

Fibroblastic/myofibroblastic tumors encompass a wide spectrum of lesions. Among them, plexiform myofibroblastoma (PM) represents a rare and distinctive entity recently described as mostly occurring in children and with a favorable prognosis. Histologically, PM shows SMA, CD34, and desmin expression in most cases, while it is negative for beta-catenin and S100. To date, the molecular mechanisms underlying PM tumorigenesis remain largely unknown. Herein, we describe a 7-year-old girl with a myofibroblastic lesion with plexiform features arising in the right deltoid region. The tumor proved positive for SMA staining, in absence of desmin, CD34, S100, and EMA expression. RNAseq analysis revealed a novel in-frame SH3PXD2B::FER fusion gene. The FER gene encodes a cytoplasmic tyrosine kinase which is implicated in several biologically aggressive tumors, where it is overexpressed and associated with EGFR recycling and stabilization. In our case, immunohistochemical analysis revealed a strong positivity for EGFR indicating an upregulation of EGFR transcription that might correlate with the novel chimeric protein involving the FER kinase domain. To our knowledge, the SH3PXD2B::FER fusion has never been reported previously. Whether the current case represents an example of a plexiform myofibroblastic tumor or a distinct tumor entity remains to be determined.