case_images: PMC11826371_01
case_images: Morphological, immunohistochemical, and molecular features of cutaneous IMT with 
  PDGFRA::USP8
   fusion. (A) Medium-power view showing a cellular tumor consisting of spindle cells arranged in loose fascicles lying in a three-dimensional pattern (hematoxylin-eosin (H&E) stain, 10x magnification). (B) On high power, the spindle cells have bland nuclei and a clear to slightly eosinophilic cytoplasm. Histiocytes, neutrophilic, and eosinophilic granulocytes (indicated with small arrows) infiltrate between the spindle cells (H&E stain, 40x magnification). (C) Low-power view of the wide local excision with a dermally to subcutaneously located, relatively well demarcated tumor (H&E stain, 0.5x magnification). (D) Spindle cells showing tram-track staining for alpha smooth muscle actin, typical for myofibroblasts (20x magnification). (E) The spindle cells displayed membranous PDGFRalpha overexpression (20x magnification).
case_images: GCC-64-e70035-g001.jpg
case_images: PMC11826371_01_GCC-64-e70035-g001.jpg
case_images: gcc70035-fig-0001
case_images: An incision biopsy revealed a cellular spindle cell neoplasm, organized in loose to compact fascicles, with a myxoid to collagenous matrix (Figure 1A). Throughout the tumor, there was a striking intervening inflammatory infiltrate, mostly consisting of histiocytes, neutrophilic, and eosinophilic granulocytes, which was remote from the area of ulceration (Figure 1B). The spindle cells showed patchy immunoreactivity for alpha SMA (Figure 1D). An additionally performed PDGFRalpha immunohistochemical staining showed strong membranous overexpression in the spindled tumor cells (Figure 1E). The excision specimen showed a relatively well-demarcated, dermal-based tumor, extending deep into the subcutaneous fat, but without infiltration of the fascia or skeletal muscle (Figure 1C).
case_images: PDGFRA::USP8
   fusion detected by targeted RNA NGS. The outlines of PDGFRA and USP8 genes are shown with the different exons and relevant functional domains indicated in red (PDGFRA) and blue (USP8). The breakpoint of PDGFRA in the fusion is situated at exon 22; the breakpoint of USP8 is situated at exon 5 (illustrated with dotted lines). IG: immunoglobulin domain; I-set: immunoglobulin I-set domain; MIT: microtubule interacting and transport domain; Rho: rhodanese-like domain; TKD: tyrosine kinase domain; UCH: ubiquitin C-terminal hydrolase domain.
case_images: GCC-64-e70035-g002.jpg
case_images: PMC11826371_01_GCC-64-e70035-g002.jpg
case_images: gcc70035-fig-0002
case_images: Up to eight mitotic figures per 2 mm2 were identified, without atypical mitotic figures. In this fusion, exon 22 of PDGFRA (breakpoint chr4:55156719, NM_006206.6) was attached to exon 5 of USP8 (breakpoint chr15:50751195, NM_5154.5); thereby keeping the kinase domain of PDGFRA intact (Figure 2).