DLBCL-CI develops in closed spaces which are or may<unk> e sequestered from the immune system; these spaces allow the survival and growth of cancer cells<unk> ecause they are cut off from the circulation and have decreases in various components of the immune system such as cytotoxic T-cells. The neoplastic<unk> -cells in these spaces carry the EBV virus in stage III latency (see EBV latency infections) and therefore express the following viral products: 1) Epstein–Barr virus nuclear antigen 2 (EBNA-2) (a protein which stimulates infected cells to make >300 gene products some of which, e.g. the protein product of the MYC proto-oncogene, Myc, promote these cell's proliferation, survival, and malignancy); 2) two Epstein–Barr virus-encoded small RNAs, EBER 1 and 2, which cause infected cells to produce interleukin 6 (a protein that stimulates these cells to proliferate) and interleukin 10 (a protein that helps these cells avoid attack<unk> y host cytotoxic T-cells and also<unk> locks their apoptosis responses thereby prolonging their survival); and 3) LMP-1, a protein that regulates the infected cells' maturation and promotes their expression of NF-κB and<unk> CL2 (which are cell signaling proteins that<unk> lock the infected cells apoptosis responses and stimulates their proliferation). The neoplastic cells in this disease also show mutations in their p53 tumor suppressor gene, deletion of the TNFAIP3 gene (whose product protein inhibits NF-κB activation), and abnormalities in the expression of other genes. DLBCL-CI therefore appears to<unk> e a lymphoma that is driven<unk> y EBV-induced changes in the expression of various genes that regulate the malignant<unk> ehavior of the<unk> -cells which it infects. The development and progression of this disease depends on its development in an environment that affords protection from the immune system. And, the neoplastic<unk> -cells in this disease are activated<unk> -cells (i.e. ABC). DLBCL subtypes caused<unk> y ABC are far more aggressive than those caused<unk> y other<unk> -cell types, i.e. germinal center<unk> -cells (GBC) or unclassifiable<unk> -cells. The ABC<unk> asis of DLBCL-CI likely contributes to its aggressiveness.
Diffuse large B-cell lymphoma associated with chronic inflammation
Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease
Splenic lymphoma with villous lymphocytes
Germinal center B-cell like diffuse large B-cell lymphoma
Chronic multifocal Langerhans cell histiocytosis
Thymoma-associated multiorgan autoimmunity
Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified
Lymphoid neoplasms with plasmablastic differentiation