TNF and primary central nervous system lymphoma: Aberrant and constitutive activation of nuclear factor (NF)-ĸB signaling pathway is a hallmark of PCNSL (Figure 5), which can be mediated through the gain of 18q21.33-q23, activating mutation of CARD11 (caspase recruitment domain family member 11) and stimulation of the B-cell receptor (BCR), tumor necrosis factor (TNF), or toll-like receptor (TLR) pathway [49].