Craniofacial involvement is associated with poor prognosis in extranodal DLBCL patients Free

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and aggressive lymphoma, with approximately one-third of cases originating in extranodal sites. Extranodal craniofacial involvement is a distinct but understudied site of DLBCL. The prognostic significance and molecular features of craniofacial involvement in extranodal DLBCL (EN-DLBCL) remain unclear.

We retrospectively analyzed 124 patients with EN-DLBCL, including 70 with craniofacial involvement and 54 without craniofacial involvement, treated with R-CHOP or R-CHOP-like regimens at our institution from 2015 to 2024. Prognostic factors and survival outcomes were evaluated using Cox regression models and Kaplan-Meier analysis, respectively. Clinical characteristics and gene mutation profiles were compared between EN-DLBCL patients with or without craniofacial involvement. Targeted next-generation sequencing (NGS) was performed on 32 tumor samples to assess gene mutations and molecular subtypes using the LymphGen algorithm.

Multivariate Cox analysis identified craniofacial involvement as an independent poor predictor for the prognosis of EN-DLBCL patients. EN-DLBCL patients with craniofacial involvement had significantly lower 5-year progression free survival (PFS) (37% vs. 52.9%, P = 0.004) and overall survival (OS) (52% vs. 59.3%, P = 0.012) compared to those without craniofacial involvement. Clinically, craniofacial involvement EN-DLBCL patients presented with lower Ann Arbor stage, better ECOG status, and lower IPI scores.Nevertheless, they exhibited a higher risk of relapse. Genomic analysis revealed frequent mutations in IGLL5, PIM1, MYD88, TMSB4X, KMT2D and BTG2, with pathway enrichment in JAK/STAT, MAPK, MYC and cell cycle signaling. Notably, only BTG2 mutation was significantly associated with poor survival in EN-DLBCL patients with craniofacial involvement (P < 0.05).

Craniofacial involvement is an independent adverse prognostic factor in EN-DLBCL patients. EN-DLBCL patients with craniofacial involvement experienced poorer survival, likely due to higher relapse rates driven by unique genetic alterations. BTG2 mutation may serve as a potential biomarker for risk stratification and targeted therapy in this subset.