LAUSR

Primary central nervous system large B-cell lymphoma (PCNS-LBCL) occurs typically in older adults and only rarely in the pediatric population. The genomic landscape of PCNS-LBCL in children and young adults (YA) is not well-characterized. In this multi-institutional study, targeted next-generation DNA sequencing and chromosomal copy number analysis was performed on a cohort of 12 pediatric and YA (age<40 years) PCNS-LBCL patients without known immunodeficiency and correlated with clinicopathologic data. Based on genomic features, we identified two subgroups: a unique "Pediatric type, MYD88-wildtype" group (median age 14 years, range 7-25 years) was characterized by absence of MYD88 mutations but frequent genetic alterations in TP53 (6/8, 75%), NFKBIE (4/8, 50%), and GNA13 (4/8, 50%); and an "adult type, MYD88-mutant" group (median age 35 years, range 25-38 years) was defined by MYD88 hotspot mutations (4/4, 100%), with frequent PRDM1 mutation/deletion (3/4, 75%), CDKN2A/B homozygous deletion (3/4, 75%), and deletions of the HLA gene cluster (2/4, 50%). Kaplan-Meier analysis demonstrated that patients with pediatric type, MYD88-wildtype PCNS-LBCL had favorable outcomes (median survival: >100 months; 5-year-overall survival: 100%). In conclusion, we have identified a new pediatric type of PCNS-LBCL that is molecularly distinct from PCNS-LBCL occurring in adults, based on an absence of MYD88 mutation, CDKN2A/B homozygous deletion, deletion of HLA gene cluster, and paucity of CD79B and PRDM1 mutations, along with an enrichment for TP53, NFKBIE, and GNA13 mutations. Patients with pediatric type, MYD88-wildtype PCNS-LBCL often have long-term survival compared to their adult counterparts.