Abstract:

Objective ·To analyze the clinicopathologic characteristics, gene mutation profile, and prognostic factors of patients with adrenal diffuse large B-cell lymphoma (DLBCL). Methods ·From March 2002 to December 2022, a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data, survival outcomes, and prognostic factors. Patients' gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes. Results ·The median age of the patients was 62 (15‒82) years and the male-to-female ratio was 2.3∶1. Among them, 63 patients (60.0%) were over 60 years old, 22 patients (21.0%) had an Eastern Cooperative Oncology Group (ECOG) performance status of two or higher, 87 patients (82.9%) were staged Ann Arbor Ⅲ‒Ⅳ, 92 patients (87.6%) had elevated serum lactate dehydrogenase (LDH) levels (above the upper limit of reference), 84 patients (80.0%) had extranodal invasion in at least two organs, 67 patients (63.8%) were of non-germinal center B-cell (non-GCB) origin, and 95 patients (90.5%) had an international prognosis index (IPI) scored over 2. With a median follow-up of 28.3 (0.7‒191.9) months, the estimated 2-year overall survival (OS) rate and progression-free survival (PFS) rate were 68.3% and 53.1%, respectively. The estimated 5-year OS rate and PFS rate were 52.6% and 44.0%, respectively. Among 93 patients who could be evaluated for clinical outcomes, 62 (66.7%) got a complete response (CR). Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS, and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS. Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D (KMT2D; n=17, 37%), Pim-1 proto-oncogene, serine/threonine kinase (PIM1; n=17, 37%), MYD88 innate immune signal transduction adaptor (MYD88; n=15, 33%), CD79b molecule (CD79B; n=13, 28%), and BTG anti-proliferation factor 2 (BTG2; n=10, 22%). Conclusion ·Age over 60 years is an adverse prognostic factor for PFS, and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL. Patients exhibited high frequencies of KMT2D, PIM1, MYD88, CD79B, and BTG2 mutations, as well as an increased proportion of the MCD-like subtype.

Key words: diffuse large B-cell lymphoma (DLBCL), extranodal, adrenal gland, clinicopathologic characteristic, gene mutation, prognostic factor