Fig. 1: Morpho-molecular characteristics of the tumors.

a–c Case No15; “young” NF (USP6-FISH: 80%). a H&E stain shows a highly cellular tumor with spindle or stellate cells arranged in a loose fascicular pattern. b Strong, diffuse, and granular cytoplasmic USP6 immunostaining (b) along with evenly distributed FISH break-apart signals containing tumor cells. c USP6-FISH reaction, all cells in the picture contain split signals. d–f Case No9; “in between” NF (USP6-FISH: 47%). d H&E stain shows plump but regular spindle-shaped fibroblasts or myofibroblasts. e A mixed population of USP6 positive and negative tumor cells (USP6 immunostaining). f USP6-FISH-reaction shows two tumor cells with split signals and three with no split signals. g–j Case No1; “old” NF (USP6-FISH: 14%). g H&E stain shows a tumor with low cellularity, composed of plump and spindle cells in a hyalinized fibrous stroma. h USP6 immunohistochemistry demonstrates a strong, but focal cytoplasmic positivity, with positive cells usually arranged in smaller groups i. FISH-USP6 split signals localized in small groups of USP6 immunopositive tumor cells (arrow). j Tumor cells with no FISH-USP6 split signals are distributed evenly in the hyalinized background (arrows). Scale bar for Fig. 1—50 µm.