Epstein-Barr Viral Load in Cerebrospinal Fluid as a Diagnostic Marker of Central Nervous System Involvement of AIDS-related Lymphoma

Abstract

Objective AIDS-related lymphoma (ARL) often involves the central nervous system (CNS). Although the diagnostic value of Epstein-Barr virus (EBV)-DNA in cerebrospinal fluid (CSF) in detecting HIV-positive primary CNS lymphoma (PCNSL) has been established, its usefulness for identifying CNS involvement of systemic ARL remains elusive. In this study, we evaluated the utility of the EBV-DNA load in CSF in identifying CNS involvement in patients with systemic ARL. Methods We retrospectively reviewed the clinical and pathological data of consecutive ARL patients managed at our clinic between January 1998 and June 2012. Sixty-two patients with ARL, including eight PCNSL patients and 52 systemic ARL patients, and 63 controls underwent CSF EBV-DNA load evaluations before receiving chemotherapy. ARL-related CNS involvement was defined as any lesion diagnosed histologically or radiologically as a lymphoma in the brain, meninges, spine, cranial nerves or oculus. Results A cut off value of 200 copies/mL predicted the presence of CNS lesions with a sensitivity of 70% and a specificity of 85% in both the PCNSL and systemic ARL patients, while a sensitivity of 75% and a specificity of 93% were obtained for systemic ARL. A cut off value of 2,000 (3.30 log) copies/mL provided the best specificity (100%), with a sensitivity of 50%. Conclusion Our results support the clinical utility of evaluating the quantitative EBV-DNA load in the CSF for the diagnosis of CNS involvement of systemic ARL as well as PCNSL.

Primary CNS Lymphoma

“…In the cART era, the frequency of HIV-associated PCNSL has fallen whilst survival has improved [91], although outcomes remain inferior to those of immunocompetent patients [92]. Surrogate measures are often used for diagnosis, using a combination of thallium-201 SPECT scanning and presence of EBV in the CSF [93, 94], therefore availability of diagnostic material for biologic studies is limited. With increasing use of intensive treatment regimens, however, histological diagnosis will have a greater influence on choice of treatment and should be obtained where feasible.…”

Epstein–Barr virus encephalitis in a renal transplant recipient manifesting as hemorrhagic, ring‐enhancing mass lesions

“…A diagnosis of EBV encephalitis may be considered when viral DNA is detected in the CSF, but the clinical significance of this finding is often unclear. EBV can be a bystander in the presence of other infections and even non‐infectious demyelinating or degenerative diseases . Approximately 15–25% of immunocompromised patients with a CNS opportunistic infection will also have a positive EBV PCR , albeit often with low viral load .…”

“…EBV can be a bystander in the presence of other infections and even non‐infectious demyelinating or degenerative diseases . Approximately 15–25% of immunocompromised patients with a CNS opportunistic infection will also have a positive EBV PCR , albeit often with low viral load . It has been suggested that sensitive EBV assays may detect latent virus carried in B cells in the CSF .…”

“…The diagnosis is challenging given the lack of specificity of cerebrospinal fluid (CSF) EBV polymerase chain reaction (PCR) in immunocompromised patients. EBV can be a ‘bystander’ in the setting of other infections or can indicate the presence of lymphoma, including central nervous system (CNS) post‐transplant lymphoproliferative disorder (PTLD) . Here, we report a case of biopsy‐proven EBV encephalitis in a renal transplant recipient, where the diagnosis was initially challenging because imaging findings raised concern for fungal infection or PTLD.…”

Epstein-Barr Virus May Contribute to Central Nervous System Involvement in HIV-positive Individuals

“…In plasma controllers (HIV RNA <20 copies/mL, n=97) CSF EBV DNA was detectable in 13 160 individuals (13.4%): it was associated with pleocytosis (50% vs. 8.4%, p=0.001), higher CSF HIV 161 RNA in those with detectable viral load (2.28 vs. 1.85 Log 10 copies/mL, p=0.011) and higher CSF 162 neopterin levels [2.81 ng/mL vs. 0.77 ng/mL, p=0.012] (Figure 3). In CSF controllers (CSF HIV RNA 163 <20 copies/mL, n=84) CSF EBV DNA was detectable in 10 individuals (11.9%): it was associated with 164 pleocytosis (66.6% vs. 6.9%, p<0.001) and border-line higher CSF neopterin (3. Several studies reported the role of EBV in immunocompromised patients and they showed that the 174 detection of EBV DNA in the CSF is a good marker of primary central nervous system lymphoma 175 (PCNSL, with sensitivity and specificity of 70% and 80%) [19] [20] [21] [22]. Some studies reported 176 the development of PCNSL in HIV-infected EBV-positive patients [23] [24] [25] [26].…”