Background
Human immunodeficiency virus (HIV)-associated primary central nervous system lymphoma (PCNSL) is a diffuse, large-cell non-Hodgkin lymphoma of B-cell origin that usually occurs in the brain (rarely in the spinal cord). It is a late complication of HIV infection. Epstein-Barr virus (EBV) is identified in almost all cases.
In the general population, PCNSL accounts for roughly 4% of primary brain tumors and 1% of all non-Hodgkin lymphoma. In HIV-infected individuals it is an important etiology of focal brain lesions (FBLs) with a reported incidence of 2–6%, at least 1000 times higher than that in the general population. [1]
Patients with PCNSL present with lethargy, headache, focal neurologic symptoms and signs, and mental status changes (see Clinical).
On CT scan or MRI, lesions are more often single than multiple and enhance with contrast. A biopsy often is required to differentiate toxoplasmosis and progressive multifocal leukoencephalopathy (PML) lesions from lymphoma (see Workup).
The prognosis is better if both chemotherapy and radiation therapy are administered. The likelihood of a diagnosis of PCNSL increases in Toxoplasma-seronegative patients with a mass effect on imaging studies if EBV DNA was detected in the CSF. Steroid therapy should be avoided whenever possible until a diagnosis has been established, as rapid necrosis of lesions may occur before biopsy. [2]
Etiology and Pathogenesis
HIV-associated primary central nervous system lymphoma (PCNSL) is typically of B-cell origin. Almost 100% of affected patients have evidence of EBV in the lymphomatous lesions and the CSF, where it is accompanied by impaired specific T-cell responses against EBV antigens. EBV transformation of chronically activated B cells is probably responsible for lymphoma development. The T cells in HIV-infected patients suppress the EBV-infected B cells less effectively. In addition, development of this opportunistic neoplasm is associated with CD4+ lymphocyte counts below 100 cells/µL. [3]
Epidemiology
United States statistics
Primary central nervous system lymphoma (PCNSL) is the second-most common mass lesion (after toxoplasmosis) in patients with acquired immunodeficiency syndrome (AIDS), occurring in up to 5% of these patients. In up to 0.6% of patients, it is the presenting feature of AIDS. A definite decline in the incidence of HIV-associated CNS lymphoma has occurred since the adoption of highly active antiretroviral therapy (HAART).
International statistics
In a retrospective analysis at a German center, the incidence of primary CNS lymphoma peaked at 5.33 per 1000 person-years from 1991-1994 (pre-HAART) and then declined to 0.32 per 1000 person-years after 1999 (post-HAART). [4]
A study of a Norwegian cancer registry (1989–2003) indicated that patients with AIDS in Norway had a 5.5% lifetime risk of developing primary CNS lymphoma. [5]
Prognosis
The prognosis in patients with HIV-associated CNS lymphoma has improved with the advent of HAART. [6, 7] In the pre-HAART era, median survival was poor, with death occurring a few weeks after diagnosis.
Survival duration is as follows:
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1 month, without treatment
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2-5 months, with radiotherapy, which is of benefit in more than 75%
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16-28 months, with radiotherapy and systemic and intrathecal chemotherapy utilizing methotrexate, thiotepa, and procarbazine (anecdotal reports)
Methotrexate may be combined with rituximab for increased efficacy. Temozolomide may also be used in those patients who do well with the treatment.
Use of HAART leads to an increase in CD4+ T cells and increases survival to more than 18 months. Some previous reports suggested that EBV-DNA levels in CSF are inversely associated with survival in HIV-related primary CNS lymphoma. [8]
Use of HAART leads to an increase in CD4+ T cells and increases survival to more than 18 months.
In a retrospective analysis by Biggar et al, 29% of patients with HIV-associated CNS lymphoma survived more than 24 months. [9]
In another study, 6 of 7 HAART-treated patients were alive at a median follow-up of 667 days. [10]
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On CT scan, cerebral lymphoma appears as focal lesions with nodular ring enhancement, mass effect, and surrounding edema. Common sites include the periventricular white and gray matter and cerebellum.
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Light microscopic examination of primary CNS lymphoma is characterized by dense infiltrates of large lymphocytes with irregular nuclei. The tumor cells can display a prominent vasocentric pattern and infiltrate blood vessel walls. Areas of necrosis may be present. Contributed by Dr Beth Levy, Saint Louis University School of Medicine, St Louis, Missouri.
