Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.

Clinicopathological Characteristics and Molecular Phenotypes of Primary Hepatic Lymphoma.

Primary hepatic lymphoma (PHL) is a rare malignant tumor, occurring in 0.016% of non-Hodgkin's lymphoma (NHL). The common histological subtype is diffuse large B-cell lymphoma (DLBCL). Due to the rarity of tumor, clinicopathological characteristics and molecular phenotypes of PHL are limited. Seven patients with PHL (primary liver DLBCL) and 13 cases of liver involvement by DLBCL diagnosed between 2014 and 2021 in our hospital were included. The genetic features were also compared between the two groups by next-generation sequencing (NGS). Differential gene expression and pathway enrichment analysis were also performed. There were some discrepancies on presenting symptoms, pathological characteristics, laboratory data, and prognosis between PHL and DLBCL-liver groups. No same mutation was found between PHL and DLBCL-liver groups by NGS. Differential gene expression analysis discovered some up- and downregulated genes in PHL compared with the DLBCL-liver group. Upregulated genes were enriched in metabolic pathways, and downregulated genes were enriched in the HTLV-1 infection pathway. PHL is a distinct entity, with unique molecular features compared to liver involvement of systemic lymphoma. Kaplan-Meier analysis showed that the prognosis of the PHL group was better than that of the DLBCL-liver group. Understanding the clinicopathological and molecular features of PHL would help to direct clinical treatment.