Nervous System Diffuse Large B-cell Lymphoma Research Articles

Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B-cell lymphoma in the North Indian population.

Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and the PD-1/PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL. We aimed to quantify the tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 expression in the PCNSL and evaluated their prognostic significance. All patients with histopathologically diagnosed PCNS-DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD-1, and PD-L1 was performed on the tissue microarray. Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12.3 years and male-to-female ratio of 0.91:1. The mean overall survival (OS) and disease-free survival (DFS) was 531.6 days and 409.8 days, respectively. Among TILs, an increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells were significantly associated with the longer OS (p = 0.037) and DFS (p = 0.023). TAMs (68CD and CD163 positive) showed an inverse relationship with OS and DFS but did not reach statistical significance (p > 0.05). Increased PD-L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p = 0.037). The TME plays a significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1-expressing immune cells is associated with better prognosis in PCNS-DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against the TME and immune check point inhibitors in this disease.

Clinicopathological features of primary central nervous system diffuse large B cell lymphoma: Experience from a Tertiary Center in North India.

Background: Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare extra-nodal Non-Hodgkin lymphoma. There is relative paucity of literature on PCNSL from Indian subcontinent. We aimed to analyze the clinicopathological features of PCNSL and categorize them into germinal center B cell (GCB) and non-GCB subtypes to assess their prognostic significance in Indian context.Methods: All patients with histopathologically diagnosed PCNSLs at our center over a period of 6 years were recruited and classified into GCB and non-GCB using Han’s algorithm (immunohistochemistry for CD10, BCL6 and MUM1). In situ hybridization (ISH) for Epstein-Barr virus (EBV)-encoded RNA was performed.Results: Eighty-six cases of PCNS-DLBCL were included with median age of 55 years. Majority of them were supratentorial in location (n = 62). All patients were immunocompetent. On immunohistochemical assessment, 69 (80.2%) were of NGCB subtype, 10 (11.6%) were of GCB subtype, and 7 (8.1%) were unclassified. Overall, MUM1, BCL-6, and CD10 expressions were seen in 69 (80.2%), 28 (32.6%), and 2 cases (2.3%), respectively. Four cases (4.6%) showed C-MYC expression. The median overall survival (OS) was 675 days. None of the factors (age, sex, location, immunomarkers, and GCB vs. NGCB phenotype) showed correlation with OS; however, BCL6 positive cases showed slight better OS (P > 0.05). All cases were negative for EBV-LMP1 on ISH.Conclusion: The majority of the CNS DLBCL belongs to non-GCB phenotype and uniformly carry poor prognosis, irrespective of their phenotype. Individual markers, such as BCL-6, MUM1, or CD10, are unable to predict outcome in PCNS-DLBCL.

Ibrutinib in primary central nervous systemdiffuse large B-cell lymphoma.

The standard regimen for the treatment of newly diagnosed primary CNS lymphoma (PCNSL) remains regimens that contain high-dose methotrexate (MTX). While these regimens can provide control for some patients, there is a dearth of options for the treatment of patients with PCNSL who cannot tolerate MTX-containing regimens, or whose cancers are refractory to MTX. In this article, we review a promising new option; ibrutinib, a Bruton tyrosine kinase inhibitor, for patients with relapsed and refractory PCNSL.