A genetically distinct pediatric subtype of primary CNS large B-cell lymphoma is associated with favorable clinical outcome

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma with CNS confinement; large B-cell lymphoma (LBCL) accounts for most PCNSL. The median age for PCNS-LBCL is 66 years, with occurrence in younger adults and pediatric cases being uncommon.(1) Although immunodeficient children have an increased risk of developing PCNSL, most cases of pediatric PCNSL in the past few decades have been reported in immunocompetent individuals. Previous studies have reported that the prognosis for PCNS-LBCL is better in pediatric and younger adults than in older adults who have a median survival of < 3 years.(2,3) Aberrant constitutive activation of the NF-kappa B signaling pathway is a hallmark of PCNS-LBCL in adults and is characterized by frequent MYD88 mutation, CD79B mutation, PRDM1 mutation/deletion, CDKN2A biallelic deletion, and HLA gene cluster deletion.(4-9) However, the molecular pathogenesis of PCNS-LBCL in children and young adults is largely unknown and may be different from that in older adults, helping to explain the divergent clinical outcomes. This multi-institutional study was conducted to investigate the molecular characteristics of pediatric and young-adult PCNS-LBCL and define associations with clinical outcomes and pathologic features. The cohort consisted of 12 patients < 40 years of age without known immunodeficiency, including 6 males and 6 females with median age at diagnosis of 17 years (range, 7-38 years). All patients were confirmed to have primary CNS confinement without systemic involvement based on staging positron-emission tomography/computed tomography and bone marrow biopsy. All patients were treated with a combination of dexamethasone, methotrexate, and rituximab, together with various accompanying agents (supplemental Tables 1-2). Tumors were uniformly composed of dense aggregates of large lymphoid cells with perivascular and parenchymal involvement, were Epstein-Barr virus (EBV) negative, and had diffuse strong immunoreactivity for B-cell markers (CD20 and PAX5). No BCL2 rearrangement and no MYC amplification or rearrangement were present (supplemental Tables 3-4). No appreciable differences in cytology or growth pattern were identifiable between these pediatric and young-adult patients with PCNS-LBCL compared with their older adult counterparts. The Institutional Review Board, Human Research Protection Program Committee at the University of California San Francisco approved this study (CHR 18-25787), which was conducted in accordance with the Declaration of Helsinki.