Three common patterns of P-STAT6 expression in PCNSL. (A) Low cellular density; absent P-STAT6 expression. (B) Low cellular density; positive P-STAT6 expression. (C) High cellular density; strong P-STAT6 nuclear expression both by tumor cells and on vascular endothelia. Patients whose tumors exhibited foci of high cellular density with positive P-STAT6 expression (C) had significantly worse outcomes than patients with tumors that were negative for P-STAT6 or tumors that were of low cellular density that scored positive for P-STAT6. Original magnification × 200 for panels A-C. Patients with intense P-STAT6 expression (C; red) experienced early progression (D) and short overall survival (E) when treated initially with high-dose methotrexate-based regimens. Green refers to tumors with sparse or absent P-STAT6 expression. (Whole-brain radiation was reserved for patients with methotrexate-refractory disease.) (Ten patients in each group; P values were calculated by log-rank test.)