AIDS-Related Primary Central Nervous System Lymphoma
Until the 1980s, primary central nervous system lymphoma (PCNSL) was a rare disease. PCNSL has increased dramatically in association with AIDS. PCNSL accounts for approximately 0.6% of initial AIDS diagnoses and is the second most frequent central nervous system (CNS) mass lesion in adults with AIDS. As with other AIDS-related lymphomas, these are usually aggressive B-cell neoplasms, either diffuse large cell or diffuse immunoblastic non-Hodgkin lymphoma. Unlike AIDS-related systemic lymphomas, in which 30% to 50% of tumors are associated with Epstein-Barr virus (EBV), AIDS-related PCNSL has been reported to have a 100% association with EBV. This percentage indicates a pathogenetic role for EBV in this disease. These patients usually have evidence of far-advanced AIDS, are severely debilitated, and present with focal neurologic symptoms such as seizures, changes in mental status, and paralysis.
Computed tomographic scans show contrast-enhancing mass lesions that may not always be distinguished from other CNS diseases, such as toxoplasmosis, that occur in AIDS patients. Magnetic resonance imaging studies using gadolinium contrast may be a more useful initial diagnostic tool in differentiating lymphoma from cerebral toxoplasmosis or progressive multifocal leukoencephalopathy. Lymphoma tends to present with large lesions, which are enhanced by gadolinium. In cerebral toxoplasmosis, ring enhancement is very common, lesions tend to be smaller, and multiple lesions are seen.[4,5,6] Use of positron emission scanning has demonstrated an improved ability to distinguish PCNSL from toxoplasmosis.[7,8]
Note: The American Joint Committee on Cancer has recently published a new edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. The PDQ Adult Treatment Editorial Board, which is responsible for maintaining this summary, is currently reviewing the new staging to determine the changes that need to be made in the summary. In addition to updating this Stage Information section, additional changes may need to be made to other parts of this summary to ensure...
PSNCL has an increased uptake while toxoplasmosis lesions are metabolically inactive. Antibodies against toxoplasmosis may also be very useful because the vast majority of cerebral toxoplasmosis occur as a consequence of reactivity of a previous infection. If the IgG titer is less than 1:4, the disease is unlikely to be toxoplasmotic. A lumbar puncture may be useful to detect as many as 23% of patients with malignant cells in their cerebrospinal fluid (CSF). Evaluating the CSF for EBV DNA may be a useful lymphoma-specific tool since EBV is present in all patients with PCNSL. Despite all of these evaluations, however, the majority of patients with PCNSL require a pathologic diagnosis.[9,10,11] Diagnosis is made by biopsy. Sometimes, a biopsy is attempted only after failure of antibiotics for toxoplasmosis, which will produce clinical and radiographic improvement within 1 to 3 weeks in patients with cerebral toxoplasmosis. PCNSL is often identified as a terminal manifestation of AIDS or on postmortem examination.
Radiation therapy alone has usually been used in this group of patients. With doses in the 35 Gy to 40 Gy range, median duration of survival has been only 72 to 119 days.[3,13,14] Survival is longer in younger patients with better performance status and the absence of opportunistic infection. Most patients respond to treatment by showing partial improvement in neurologic symptoms. Autopsies have revealed that these patients die of opportunistic infections as well as tumor progression. Treatment of these patients is also complicated by other AIDS-related CNS infections, including subacute AIDS encephalitis, cytomegalovirus encephalitis, and toxoplasmosis encephalitis. Spontaneous remissions have been reported after highly active antiretroviral therapy.