Diffuse Large B-cell Lymphoma

The germinal center (GC)-like type is characterized by high levels of immune infiltrate containing considerable numbers of follicular dendritic cells, lymphatic endothelial cells, non-malignant B cells, and various T cell subpopulations including Tregs and follicular helper T cells. Immune inflamed. Low percentage of malignant cells. Low tumor mutational burden (TMB). The germinal center B-cell (GCB) molecular type is predominant.

The mesenchymal type is highly fibrotic with a low lymphocyte and macrophage infiltration. Immune non-inflamed. Cancer associated fibroblasts (CAF) are abundant. Elevated angiogenesis and extracellular matrix (ECM) remodeling processes are observed. TGF-β and HIF1 signaling pathways are often upregulated. Mutations in genes associated with the antigen-presentation machinery are frequent. Most cases of primary mediastinal B-cell lymphomas belong to this type. The germinal center B-cell (GCB) molecular type is predominant.

The immune-inflamed type is characterized by high immune infiltrate levels containing considerable numbers of macrophages, neutrophils, and T cells. CD4/CD8 T-cell ratio is shifted to CD8 T cells. High PD-1 expression on cytotoxic T cells is commonly observed. Active immune escape mechanisms including high IDO-1 and PD-L1 expression. Low percentage of malignant cells. Low tumor mutational burden (TMB). The activated B-cell (ABC) molecular type is predominant.

The immune-depleted type is characterized by low immune and stromal infiltrate. Immune non-inflamed, non-fibrotic. High percentage of malignant cells. This type also demonstrates increased chromosomal instability (CIN). Aberrant DNA hypermethylation reflecting immune escape is observed.