Primary effusion lymphoma
Primary effusion lymphoma | |
---|---|
Specialty | Hematology, oncology, virology |
Causes | Chronic viral infection with KSHV/HHV8 or HIV |
Prognosis | Guarded |
Primary effusion lymphoma (PEL) is classified as a
PEL typically occurs in individuals who are
Formally, PEL is defined by the
Primary effussion lymphoma is an extremely aggressive cancer that is highly resistant to various chemotherapy treatments. It has carried a median survival time of ~5 months,[8] with overall survival rates at 1, 3, and 5 year of only 30, 18, and 17%, respectively. In many cases, however, this high mortality reflects, at least in part, the lethality of its underlying predisposing diseases, particularly HIV/AIDS in HIV-infected individuals. New treatment strategies, including those directed at its underlying predisposing diseases, may improve the prognosis of PEL.[9]
Presentation
Individuals diagnosed with PEL most commonly (>33% of all cases) present with advanced
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
As a probable result of their excessive proliferation, prolonged survival, and ability to avoid attack by a weakened
Diagnosis
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. The diagnosis is supported by microscopic examination of
KSHV/HHV8-negative primary effusion lymphoma
Effusion-based lymphoma, KSHV/HHV8-negative (also termed Type II PEL) has been described by some researchers. These cases closely resemble KSHV/HHV8-positive (also termed Type I PEL) but have yet to be defined by the World Health Organization (2017). Compared to Type I PEL, Type II PEL occurs more often in older individuals, is less often associated with EBV, and more often afflicts individuals who lack evidence of being immunocompromised.[1] That is, the majority of HHV-8-negative EBL cases do not evidence a potentially PEL causative agent, such as HIV, EBV, HCV, or iatrogenic immunodeficiency, except for old age and, in 20% to 40% of cases, the presence of hepatitis C virus infection.[17] Type II PEL also tends to involve malignant plasmablasts, anaplastic cells, and/or Reed-Sternberg-like cells that have somewhat different expression patters of protein markers (e.g. the malignant cells in Type II PEL frequently express CD20 but often do not express CD30) and gene abnormalities (e.g. the malignant cells in Type II PEL more commonly evidence rearrangements in their Myc, BCL2, and BCL6 genes) than the malignant cells in Type I PEL. The response to treatment and prognosis of Type II PEL is poor[1] but may be somewhat better than the treatment-responsiveness and prognosis of Type I PEL.[17] One factor that appears to improve the treatment of Type II PEL is the addition of rituximab (a monoclonal antibody directed against and killing CD20-bearing cell) to the intensive chemotherapy regimens used to treat Type I PEL: the malignant cells in Type II PEL commonly express CD20 whereas the malignant cells in Type I PEL rarely express this cell surface marker. However, there are several cases of KSHV/HHV8-negative EBL that presented with pericardial effusions without evidence of more extensive disease that have experienced complete responses and favorable prognoses without chemotherapy or other cancer treatment (including rituximab) after simple drainage of the effusion. These cases suggest that, in addition to the presence of rituximab-sensitive CD20-bearing malignant cells, Type II PEL may be a less severe disease than Type I PEL, at least in certain cases.[17]
Treatment
PEL is generally resistant to cancer chemotherapy drugs that are active against other B-cell lymphomas and therefore carries a poor prognosis.[18] Overall median and 1 year survival rates in a series of 28 patients treated with chemotherapy for PEL were 6.2 months and 39.3%, respectively. 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%. A second study using CHOP-like regimens or one of these regimens plus methotrexate also produced better results with the latter regimens: 5 year survival rates for the CHOP-like and CHOP-like plus methotrexate regimens were 34.4% and 45.7%, respectively.[4] A review of 105 PEL cases reported median survival times, 1 year, 3 year, and 5 year survival rates of 4.8 months, 30%, 18%, and 17%, respectively. In this study, patients with advanced Ann Arbor Stage III or IV disease had a particularly poor survival rate at 1 year of 25%; this compared to a rate of 42% for patients with stage I or II disease.[5]
Anti-viral drugs directed against
History
PEL was first described in 1989 as a malignant B cell-derived non-Hodgkin lymphoma that developed in three individuals afflicted with HIV/AIDS.[22] In 1995, a group of researchers found DNA sequences that identified KSHV/HHV8 sequences in 8 lymphomas in the malignant cells of patients infected with the HIV; all 8 patients had effusions containing malignant cells in their pleural, pericardial, or peritoneal spaces and had malignant cells in their effusions that evidenced the Epstein-Barr viral genome.[23] Nadir and colleagues termed this syndrome of findings pulmonary effusion lymphoma in 1996.[24] During the years following these initial reports, several cases of PEL were found to be KSHV/HHV8-negative, i.e. occurring in individuals with no evidence of being infected with KSHV/HHV8, or to be manifested by solid tumors that were not associated with effusions, i.e. cases of extracavitary PEL.[17]
See also
References
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