Clonal Evolution in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Primary central nervous system diffuse large B-cell lymphoma (CNS DLBCL) is an aggressive malignancy.
• Extranodal relapse occurs in a subset of CNS DLBCL cases, necessitating further investigation into relapse patterns and mechanisms.

Observation:

• A case of CNS DLBCL is presented, which relapsed 18 months post-diagnosis in the testis and bilateral adrenal glands.
• Both primary and relapsed tumors exhibited identical morphology, phenotype, cytogenetics, and clonal origin.
• Next-generation sequencing identified a shared MYD88L265P mutation and a de novo CD79B Y196S mutation in the relapsed tumor.

Findings:

• The mutation pattern suggests evolution from a common progenitor clone, with MYD88L265P as the founder mutation.
• A meta-analysis confirmed a high frequency of concurrent MYD88L265P and CD79B mutations in primary CNS and testicular DLBCL.
• These mutations implicate B-cell receptor and NF-κB pathway activation in lymphomas colonizing immune-privileged sites.

Implications:

• Targeted next-generation sequencing for somatic mutations is valuable in relapsed DLBCL.
• This approach can confirm the activated B-cell (ABC) phenotype and provide crucial information for therapeutic decisions.
• Understanding the genetic landscape of relapsed DLBCL can guide treatment strategies for these challenging lymphomas.