IRF4 protein expression is associated with IRF4 CNAs in PTCLs. (A) Eighty-three percent of PTCLs with extra copies of IRF4 were IRF4 protein positive, compared with 39% of cases without extra copies (P = .0002). (B) PTCLs with extra copies of IRF4 had a higher mean percentage of tumor cells with IRF4 staining than those without extra copies (P = .0001). (C) PTCL, not otherwise specified (NOS), involving the skin. IHC shows no evidence of IRF4 expression (left panel, ×20; middle panel, ×400). IRF4 FISH using a break-apart probe shows a normal signal pattern (2 intact red/green fusion signals; right panel, ×600). (D) ALCL, anaplastic lymphoma kinase (ALK) positive, involving the skin. IHC shows nuclear IRF4 expression (left panel, ×20; middle panel, ×400). IRF4 FISH shows multiple intact copies of the IRF4 gene (6 fusion signals in cell shown; right panel, ×600). (E) The germ-line SNP rs12203592-T was significantly associated with IRF4 positivity in PTCLs (P = .03). (F) The germ-line SNP rs872071 was not significantly associated with IRF4 positivity (P = .39).