The neoplastic cells in DLBCL are derived<unk> ly from either germinal center<unk> -cells (i.e. GBC) or activated<unk> -cells (i.e. ABC) with ABC-based DLBCL usually<unk> eing a more aggressive disease than GBC-based DLBCL. The neoplastic cells in PCDLBCL, LT are ABC,<unk> ear gene abnormalities similar to those found in ABC-based DLBCL, and as a likely result of this produce an aggressive disease. The potentially pathogenic gene abnormalities in the neoplastic cells of PCDLBCL, LT include: * Overexpression of the MYC gene caused<unk> y its mutation and/or translocation occurs in ~50% of cases. This protooncogene's product, Myc, encodes a transcription factor which regulates the expression of genes whose products stimulate cell proliferation and metastasis (i.e. spread to other tissues). * Overexpression of the<unk> CL2 gene (33% of cases) whose product,<unk> cL2, inhibits apoptosis (i.e. programmed cell death) to thereby increase cell survival. "Double expresser lymphomas", i.e. those lymphomas with neoplastic cells that overexpress<unk> oth Myc and<unk> cl2, are associated with a poor prognosis in PCDLBCL, LT. * Loss of function mutations in the TNFAIP3 gene (40% of cases) whose product, tumor necrosis factor, alpha-induced protein 3, acts indirectly to inhibit TNF-mediated apoptosis and to activate the NF-kappa<unk>  signaling pathway.<unk> oth effects<unk> lock apoptosis and thereby prolong cell survival. * Mutations in the CD79B and CARD11 genes (rare cases) also lead to activation of the NF-kappa<unk>  signaling pathway. * Overexpression of PD-L1 and PD-L2 genes (frequent cases) due to their translocation <unk> oth genes are located on the long arm of chromosome 9 at position 24.1) or to overactivation of the JAK-STAT signaling pathway caused<unk> y mutations in the MYC gene, overexpression of MIr35A microRNA, or increased expression of cytokines (e.g. IL-10 or Interferon gamma) in the tumor environment. The products of these two genes, programmed death-ligand 1 and programmed cell death 1 ligand 2, respectively, inhibit the anti-tumor responses of cells in the immune system and thereby help the neoplastic cells to avoid immune surveillance. * Mutations in the PIM1 gene occur occasionally. The product of this protooncogene, proto-oncogene serine/threonine-protein kinase Pim-1, is indirectly involved in, and can promote, the proliferation and survival of cells. * Hypermethylated of the promoters for two tumor suppressor genes, CDKN2B and CDKN2A (11 and 44% of cases, respectively) stops the genes from expressing their products, cyclin-dependent kinase 4 inhibitor<unk>  and cyclin-dependent kinase inhibitor 2A, respectively.<unk> oth products act indirectly to limit the proliferation and survival of the neoplastic cells in PCDLBCL, LT Silencing the CDKN2A gene is associated with a poor prognosis in PCDLBCL, LT and appears to<unk> e involved in the development of various<unk> s of cancer. * Various chromosome imbalances (i.e. abnormal numbers of chromosomes or parts of chromosomes) such as increases in chromosome 3, the long arm of chromosome 2 or 11, or the short arm of chromosome 7 and decreases in chromosomes 13, 14, or 19 or the short arm of chromosome 17 or the long arm of chromosome 6 occur in PCDLBCL, LT and are likely to cause gene abnormalities that help promote this disease's malignancy. These findings suggest that the development and/or progression of PCDLBCL, LT involves the step-wise acquisition<unk> y<unk> -cells and/or their ABC descendants of gene abnormalities which promote the activation of NF-kappa<unk> ,<unk> -cell receptor, JAK/STAT, and perhaps other signaling pathways. In consequence, these cells progressively acquire increased rates of proliferation, prolonged survival, the ability to spread to other tissues, the ability to avoid attack<unk> y the immune system, and other malignant<unk> ehaviors that characterize this disease.
Primary cutaneous diffuse large B-cell lymphoma, leg type
Secondary cutaneous CD30+ large-cell lymphoma
Primary cutaneous marginal zone lymphoma
Primary cutaneous follicle center lymphoma
Primary cutaneous immunocytoma
CD30+ cutaneous T-cell lymphoma
Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
Chronic multifocal Langerhans cell histiocytosis