In addition, disease that initially involves the testes, breast, or uterus has a relatively high rate of spreading to the central nervous system while disease initially involving the kidneys, adrenal glands, ovaries, or bone marrow has a high rate of spreading to other organs, including the central nervous system. All of these cases as well as cases initially involving the central nervous system have relatively poor to very poor prognoses. Cases initially involving the stomach, thyroid, or a single bone site have relatively good prognoses. Pathophysiology
Most cases of DLBCL, NOS appear to result at least in part from the step-wise development of gene changes such as mutations, altered expressions, amplifications (i.e. increases in the number of copies of specific genes), and tranlocations from normal sites to other chromosomal sites. These changes often result in gains or loses in the production or function of the product of these genes and thereby the activity of cell signaling pathways that regulate the maturation, proliferation, survival, spread, evasion of the immune system, and other malignant behaviors of the cells in which they occur. While scores of genes have been reported to be altered in DLBCL, NOS many of these may not contribute to DLBCL, NOS. Changes in the following genes occur frequently in, and are suspected of contributing to, this diseases development and/or progression. BCL2: This gene is a protooncogene, i.e. a normal gene that can become cancer-causing when mutated or overexpressed. Its product, Bcl-2 protein, regulates cellular apoptosis (i.e.
Over the last few years, however, many investigators have come to feel that hepcidin is the central actor in producing anemia of chronic inflammation. Hepcidin provides a unifying explanation for the condition, and more recent descriptions of human iron metabolism and hepcidin function reflect this view.In addition to effects of iron sequestration, inflammatory cytokines promote the production of white blood cells. Bone marrow produces both white blood cells and red blood cells from the same precursor stem cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This effect may be an important additional cause for the decreased erythropoiesis and red blood cell production seen in anemia of inflammation, even when erythropoietin levels are normal, and even aside from the effects of hepcidin. Nonetheless, there are other mechanisms that also contribute to the lowering of hemoglobin levels during inflammation: (i) Inflammatory cytokines suppress the proliferation of erythroid precursors in the bone marrow. ; (ii) inflammatory cytokines inhibit the release of erythropoietin (EPO) from the kidney; and (iii) the survival time of circulating red cells is shortened.In the short term, the overall effect of these changes is likely positive: it allows the body to keep more iron away from bacterial pathogens in the body, while producing more immune cells to fight off infection. Almost all bacteria depend on iron to live and multiply. However, if inflammation continues, the effect of locking up iron stores is to reduce the ability of the bone marrow to produce red blood cells.