[3] The extracavitary tumors may develop in lymph nodes, bone, bone marrow, the gastrointestinal tract, skin, spleen, liver, lungs, central nervous system, testes, paranasal sinuses, muscle, and, rarely, inside the vasculature and sinuses of lymph nodes.

Individuals with the cavitary form of PEL present with symptoms due to effusions in the pleural cavity (e.g. shortness of breath), pericardium (e.g. chest pain/discomfort, hypotension, shortness of breath), peritoneal cavity (e.g. abdominal swelling), or, much less often, joints (e.g. swelling), the epidural space (e.g. central nervous system symptoms), or breast implants (e.g. breast swelling/pain/malformation).

[4] Individuals with extracavitary PEL present with lesions in the lung, central nervous system, gastrointestinal tract,[4] and/or lymph nodes.

[1] 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).

[8] PEL develops in patients that have predisposing diseases that reduce the immune systems ability to attack precancerous and cancerous cells.

[11] Finally, some studies suggest that EBV cooperates with KSHV/HHV8 to cause PEL, perhaps by enhancing the ability of KSHV/HHV8 to establish their pro-malignant latency phase in infected cells.

[3] As a probable result of their excessive proliferation, prolonged survival, and ability to avoid attack by a weakened immune system, the malignant cells in PEL exhibit a high degree of genomic instability, i.e. alterations in the structure and/or expression of their genetic material which are associated with the development and/or progression of PEL.

[4] In classical cavitary cases, the diagnosis of PEL may be suspected based on its presentation as effusions in one or more bodily cavities in individuals with a history of the immunodeficiencies cited above.

[1] By definition, individuals with PEL are infected by Kaposi's sarcoma-associated herpesvirus (HHV-8 or KSHV/HHV8)[13][14] and therefore evidence malignant cells that express products of this virus such as LANA1.

[1] In most cases, these individuals are also infected with EBV[15] and therefore evidence malignant cells that express products of this virus such as EBER1/2 nuclear RNA's.

[17] PEL is generally resistant to cancer chemotherapy drugs that are active against other B-cell lymphomas and therefore carries a poor prognosis.

In this study, the complete response rate (presumed to be temporary) to a standard CHOP chemotherapeutic regimen (i.e. cyclophosphamide doxorubicin, vincristine, and prednisone) was only 10% whereas a more intensive CHO chemotherapy regimen which included high dose methotrexate and bleomycin achieved a compete response rate (presumed temporary) of 70%.

[5] Anti-viral drugs directed against Cytomegalovirus (i.e. cidofovir, ganciclovir, and valganciclovir) have been reported to produce complete presumed temporary responses in individual cases of PEL while drugs directed against HIV in patients with HIV+ PEL have achieved presumed temporary median response and 5-year survival rates of 0.7 months and 28%, respectively.

The National Comprehensive Cancer Network (NCCN) guideline recommends treating HIV/AIDS-related PEL with antiviral therapy in combination with aggressive chemotherapy regimens such as DA-EPOCH, cyclophosphamide, doxorubicin, and etoposide, or CHOP.

The efficacy of rituximab in CD- PEL may be due to the ability of this antibody to kill non-malignant CD+ 20 lymphocytes and thereby their potential to promote the disease.