AIDS-Related Primary Central Nervous System Lymphoma

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Epidemiology and the link with Epstein-Barr virus

Patients who have AIDS have a markedly greater risk of developing PCNSL compared with the general population. Patients who have AIDS PCNSL are more likely to be men, with a median age of presentation in the late fourth decade as opposed to the sixth or seventh decade in immunocompetent patients [4]. In the period before highly active antiretroviral therapy (HAART), the relative risk of PCNSL was estimated to be over 1000-fold in HIV-infected individuals and as great as 3600-fold [14]. Since the

Histopathology

Nearly all PCNSLs are of B-cell origin. In the AIDS setting, diffuse large B-cell lymphoma and its immunoblastic variant are the dominant morphologies; small noncleaved cell lymphoma (Burkitt's or Burkitt-like) and other morphologies are less frequent [4]. Polymorphous or atypical features are common, making subclassification at times difficult [4]. The malignant lymphocytes are characterized by a high mitotic index and a diffuse growth pattern, classically with an angiocentric distribution and

Radiographic features

The radiographic appearance of PCNSL can differ substantially in the AIDS versus non-AIDS setting. Differentiating PCNSL from toxoplasmosis is one of the most frequently encountered diagnostic challenges in the patient with AIDS who has an intracranial mass lesion, particularly if the process appears multifocal.

Baseline Evaluations

Because AIDS-related systemic lymphomas have a predilection for extranodal dissemination, including the central nervous system (CNS), evaluation for systemic lymphoma in the patient who has AIDS PCNSL was once routinely recommended [6]. In patients who have AIDS PCNSL, however, evaluation for occult systemic lymphoma—including CT scan of the chest, abdomen, and pelvis and bone marrow biopsy—has a low diagnostic yield [6]. This finding was confirmed in a multicenter study of AIDS PCNSL in which

Treatment options

The median survival of patients who have AIDS PCNSL is 1 to 2.5 months with supportive care alone [11], [70]. Palliative whole-brain radiation is the mainstay of managing most patients because surgical resection is not curative and there are barriers to chemotherapy.

Epstein-Barr virus–targeted therapies

The consistent association of EBV and PCNSL suggests the possibility that the virus might in some way be a target for therapeutic interventions. This idea has attracted considerable attention but clinical successes have been limited at best. In this section, the authors consider various approaches to targeting the virus and what limits their application to AIDS PCNSL. Three general approaches have been explored: immune targeting of viral antigens, disruption of viral functions, and the use of

Summary

Because survival of patients infected with HIV has improved with HAART, more patients diagnosed with PCNSL may become candidates for chemotherapy. The role of chemotherapy is far from established, however, and there are clear limitations to dose-intensive approaches in the setting of advanced HIV infection. Because of the rarity of this lymphoma, multicenter collaborations are needed to address these and other fundamental management questions. Further insights into the biology of AIDS PCNSL may

Acknowledgments

The authors thank Adam El-Dieb, MD, Ayse Aralasmak, MD, and William Lavely, MD, for assistance with the neuroimages, and Sharon Swierczynski, MD, PhD, and Peter Burger, MD, for assistance with the pathology slides.

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    Supported in part by grants P50 CA96888 and UO1 CA70062 to R.F. Ambinder.

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