HIV-Related Primary Central Nervous System Lymphoma: Still a Diagnostic Challenge

Abstract

Primary central nervous system lymphoma (PCNSL) occurs in 1% to 3% of all patients with AIDS, typically in the course of severe immunodeficiency and prior AIDS-defining illnesses. The differential diagnosis of a space-occupying cerebral lesion is broad in this setting and includes toxoplasmosis and, less commonly, fungi, tuberculosis, gummatous lesions, gliomas and astrocytomas. Only tissue obtained from stereotactic brain biopsy can reliably differentiate PCNSL from cerebral toxoplasmosis in most cases, but this invasive examination implies some adverse issues that must be carefully taken into account. Hence, more effective and safer diagnostic tools are warranted in order to avoid delay in diagnosins a disease that, if untreated, has a mortality rate of 75% within 45 days.

Recent studies have shown that Epstein-Barr Virus (EBV) in cerebrospinal fluid (CSF) is associated with HIV-PCNSL in virtually 100% of cases, whereas it is absent in almost all cases of brain tumours other than PCNSL. Thus, the detection of such virus in CSF may now be considered both a sensitive and specific tumour marker.

In addition, we investigated the effectiveness of 201-Thallium Single Photon Emission Computed Tomography (201Tl-SPECT) as a novel diagnostic tool for intracerebral lesions in this setting. 201Tl is a metabolic tracer which behaves as a kalium analogue: it is uptaken in viable tumours and its imaging is related to cell growth rate and blood flow and is unaffected by impaired permeability of the blood-brain barrier in lesions other than tumours and by steroid administration. On the contrary, infectious diseases, haematomas and radiation necrosis do not cause 201-Tl accumulation. Thus, the uptake ratio (between the region of the brain under investigation and its uninvolved counterpart has been shown to act as an improved tool, with respect to conventional imaging, in differentiating intracerebral neoplastic from nonneoplastic lesions.

It is suggested that an intermediate step should be included in the diagnostic algorithm of HIV-associated space occupying lesions: the finding of CSF positivity for EBV, together with a SPECT featuring hypermetabolic lesions is likely to be highly indicative of PCNSL, and brain biopsy could, therefore, be avoided. When the CSF is negative for EBV and the SPECT shows hypometabolic lesions, or when only one of the two investigations suggests PCNSL, a brain biopsy could be advisable if an initial antitoxoplasmosis therapy has failed.

These coupled tools should at last allow an earlier diagnosis of HIV-PCNSL and, as a consequence, prompter treatment. Even though both whole brain RT and multimodality treatment schedules ought to be considered rarely curative at present, any non-invasive procedure allowing earlier diagnosis of this disease would render possible earlier treatment and thus help improve the patient's quality of life and survival.

We believe that this algorithm serves as a demonstration of the resources offered by a multidisciplinary approach in such an important field, open to future diagnostic and therapeutic investigations.