Clinicopathologic characteristics, mutations, and prevalence by lymphoma subtypes. (A) Clinicopathologic characteristics and mutations in patients with CNS or systemic (non-CNS) recurrence of DLBCL. Tumors were grouped into genomic subtypes according to the LymphGen classifier and hc. Boxes list definitions of the hc subgroups, and respective clusters are highlighted in the heatmap; only genes mutated in >10% patients are included. (B) Prevalence of mutated genes in groups with CNS or systemic (non-CNS) recurrence. Only genes mutated in >10% patients are included; no single gene was associated with CNS recurrence after adjustment for multiple testing. (C) Time from diagnosis to progression, stratified by type of recurrence. Median time to recurrence was 10 months (95% confidence interval, 8-11) and did not significantly differ between groups (log-rank P = .70). (D) Overall survival after recurrence. Median survival was shorter for patients with CNS recurrence (6 vs 17 months), but the difference was not statistically significant (log-rank P = .21). (E) Comparison of prevalence of specific LymphGen-determined DLBCL subtypes between patients with CNS or systemic-only (Sys) recurrence and unselected (Uns) DLBCL cases from 2 aggregated cohorts (N = 462)^9,12,17 ; the MCD subtype was significantly more prevalent among patients with CNS recurrence (38% vs 8%, P = .003), whereas no CNS-relapsed tumor classified as ST2 or BN2 subtype. (F) Comparison of DLBCL subtypes defined by the hc between patients with CNS or systemic-only (Sys) recurrence and unselected DLBCL cases (Uns); the hc-MCD subtype was significantly more prevalent in tumors with CNS recurrence (46% vs 17%, P = .017), whereas other subtypes did not differ between groups.