mRNA in situ hybridization in HRS cells identifies patients with inferior PFS and OS in an independent validation cohort (n = 132). (A) A representative CSF1R-positive case is shown highlighting cytoplasmic positivity in a Hodgkin cell (orange arrow) and macrophages in the reactive infiltrate. (B) A representative CSF1R-negative case is shown with no staining in the multinucleated HRS cells (orange arrows). (C) PFS according to CSF1R mRNA in situ hybridization. (D) OS according to CSF1R mRNA in situ hybridization. (E) PFS according to a combined CD68 IHC/CSF1R in situ hybridization score. (F) OS according to a combined CD68 IHC/CSF1R in situ hybridization score.