Clinical and Molecular Differences in Diffuse Large B-Cell Lymphoma with and without Testicular Involvement: A Cbioportal Analysis

Background: Diffuse Large B-Cell Lymphoma (DLBCL) exhibits diverse clinical behaviors. Testicular DLBCL can have distinct clinical presentation and genetic landscape compared to non-testicular DLBCL. This study aims to characterize these differences to improve diagnostic precision and therapeutic strategies.

Methods: By using cBioPortal (1), we detected 1,658 DLBCL cases from six studies that were previously published, focusing on 722 cases with recorded testicular involvement status. We compared demographic data, survival, tumor mutational burden (TMB), and gene alteration profiles between groups with and without testicular involvement in DLBCL.

Results: Among the 722 cases, 80 (11.1%) had testicular tumor infiltration. Patients with testicular DLBCL presented at a significantly younger age (mean is 60.82 years, 95% CI: 59.49-61.87) compared to those without testicular involvement (mean is 67.56 years, 95% CI: 65.05-70.07). Moreover, testicular involvement was associated with a higher incidence of pleural and intraabdominal lesions (p=2.11E-3 and p=1.53E-4, respectively). Both groups had statistically similar overall survival. Consistent with previous small cohort studies, mutational analysis revealed that, MYD88 gene, a critical mediator in the NF-kB signaling pathway which influences B-cell survival and proliferation, showed significant mutation enrichment in the testicular group (45.88% vs. 15.8% in the non-testicular group, p=1.42E-9). Other mutations such as PIM1(p=2.694E-4), CDKN2A(p=1.844E-3), and ARID1A(p=6.845E-3) were also significantly higher in the testicular group despite similar TMB in both groups, suggesting a distinct pathogenic mechanism in these lymphomas.

Conclusions: Patients with testicular DLBCL present at a younger age compared to the patients with non-testicular DLBCL. The high prevalence of MYD88 mutations in the testicular subgroup suggests potential therapeutic targets and warrants further investigation into tailored treatment protocols for this population. In addition, non-testicular DLBCL patients with MYD88 mutations might benefit from regular testicular examination with ultrasound for early detection.

No relevant conflicts of interest to declare.