Primary effusion lymphoma (ORPHA:48686)
Primary effusion lymphoma (PEL) is a large B-cell lymphoma located in the body cavities, characterized by pleural, peritoneal, and pericardial fluid lymphomatous effusions and that is always associated with human herpes virus-8 (HHV-8).
Epidemiology
The prevalence is unknown but it accounts for less than 1% of non-AIDS related lymphomas and approximately 3% of AIDS-related lymphomas.
Clinical description
PEL is most frequently found in young men that are positive for HIV or have pre-existing AIDS. Very rare non-HIV related cases have been reported but these patients are almost all elderly or immunodeficient due to another cause. Peritoneal, pleural, and pericardial fluid lymphomatous effusions are observed with, in the majority of cases, no mass-like extranodal extension of lymphoma. Symptoms of PEL depend on the body cavity affected and are caused by the accumulation of the malignant effusion. Pleural or pericardial disease has dyspnea as a symptom while abdominal distension is experienced in peritoneal disease. PEL is usually extremely aggressive and dissemination of lymphoma to distant sites, opportunistic infections and HIV-related complications are often fatal. In the rare HIV-negative cases the outcome may be better.
Etiology
The precise etiology is unknown. PEL is always associated with HHV-8, also known as Kaposi sarcoma-associated herpes (KSHV) and is most frequently found in immunodeficient patients, especially those with advanced AIDS. An infection with Epstein-Barr virus (EBV) is also present in the majority of PEL cases. The gene products of these viral genomes are thought to inhibit cell apoptosis and promote uncontrolled cell division and subsequent neoplastic transformation.
Diagnostic methods
Body cavity fluid is analyzed cytologically and by flow cytometry for the presence of clonal large neoplastic cells (with immunoblastic, anaplastic or plasmablastic appearances) with prominent nucleoli, round to irregular nuclei and occasionally vacuolated cytoplasm. To be given a diagnosis with PEL an infection with HHV-8 must be present. A latency-associated nuclear antigen-1 (LANA-1) assay detects any evidence of HHV-8 in tissue samples. Complete blood counts and positron emission tomography/computed tomography (PET/CT) scans should also be performed to determine the extent of the disease.
Differential diagnosis
Differential diagnoses include diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, which can present with lymphomatous effusion, anaplastic large cell lymphoma (ALCL; see these terms) and pyothorax-associated lymphoma (PAL).
Management and treatment
PEL is usually refractory to conventional chemotherapy and treatment guidelines are not well defined. Highly active antiretroviral therapy (HAART) should be administered concurrently with chemotherapy in all HIV positive PEL patients. The chemotherapy regimen cyclophosamide, doxorubicin, vincristine and prednisone (CHOP) is most commonly used. Research into molecular targeting therapy for the treatment of PEL is ongoing. There is a single case report of a durable remission for more than 18 months with the use of sobuzoxane.
Prognosis
PEL has a very poor prognosis with an average life expectancy of 3-4 months after diagnosis. Rare patients with HIV-negative PEL have durable progression free survival after chemotherapy.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Ephraim HOCHBERG