At diagnosis, more than 50% of individuals afflicted with either cavitary or extracavitary PEL have or report a history of B symptoms (i.e. fever, weight loss, night sweat). Laboratory examination in all PEL cases often show anemia, low blood levels of platelets, high serum levels of IL6, and high levels of circulating KSHV/HHV8. Pathophysiology
PEL develops in patients that have predisposing diseases that reduce the immune systems ability to attack precancerous and cancerous cells. Initially, KSHV/HHV8 viruses infect plasmablasts to establish a latency state in which the viruses express malignancy-promoting genes (see KSHV/HHV8 genes). Products of these viral genes include: 1) LANA-1, which inhibits host cells  p53 protein thereby reducing these cells apoptosis (i.e.
programmed cell death) response to injury, and also inhibits the activity of host cells retinoblastoma protein thereby increasing these cells proliferation; 2) vcylin, an analog of host cell cyclin, which binds RB to increase these cells proliferation; 3) vFLIP, which inhibits host cells apoptosis and activates these cells NF-κB signaling pathway to prolong their survival; 4) various protein isoforms of kaposin which stimulate host cells to release cytokines (e.g., GM-CSF and IL-6) that act back on these cells to stimulate their growth; 5) vIL6, a viral analog of host cells IL-6 which, while not often expressed, induces these cells to produce VEGF, a cytokine that feeds back on these cells to inhibit their apoptosis and to increase the permeability of nearby blood vessels thereby promoting the formation of effusions; 6) K1 protein which promotes the malignancy of host cells; 7) G-protein coupled receptor protein which promotes host cells proliferation and survival; and 8) several viral microRNAs that promote host cells to proliferate, inhibit these cells apoptosis, and stimulate the vascularization of nearby small blood vessel to promote effusions. While HIV/AIDS is associated with a wide range of cancers, including those involving B-cells such as plasmablastic lymphoma, the development of these cancers is commonly attributed to co-infection with oncogenic viruses (e.g. KSHV/HHV8, EBV): the direct role of HIV/AIDS in promoting PEL is unclear.