HIV-Associated Primary CNS Lymphoma
The most likely diagnosis is HIV-associated primary CNS lymphoma (PCNSL), and you should immediately initiate rituximab plus high-dose methotrexate (3 g/m²) combined with fully active antiretroviral therapy (ART) after confirming the diagnosis with CSF EBV-DNA PCR. 1
Diagnostic Reasoning
The clinical presentation is classic for HIV-PCNSL in a severely immunocompromised patient:
- CD4 count of 15 cells/µL indicates profound immunosuppression, the typical setting for HIV-PCNSL 1, 2
- EBV detected in CSF has 87.5-100% sensitivity and 100% specificity for HIV-PCNSL when brain mass lesions are present 3
- MR spectroscopy showing elevated choline peak with loss of NAA is the characteristic tumoral pattern that distinguishes lymphoma from infectious processes like toxoplasmosis 4
- Multiple lesions (three) are common in HIV-PCNSL, occurring in approximately 71% of cases 5
- Necrotic core is frequently seen in HIV-PCNSL on imaging 5
Immediate Diagnostic Steps
Confirm the diagnosis without delay using these specific tests:
- CSF analysis for EBV-DNA by quantitative PCR is the single most important diagnostic test, positive in >96% of HIV-PCNSL cases 1, 6
- Serum LDH measurement as an additional tumor marker 1
- CSF cytology and flow cytometry if lumbar puncture can be safely performed 1
- FDG-PET/CT scan to exclude systemic lymphoma involvement, which would change the diagnosis to secondary CNS lymphoma 1
- Ophthalmology assessment to identify lymphomatous involvement in 5-20% of cases 1
- Testicular ultrasound in men to exclude occult systemic disease (present in 8% of cases) 1
Brain biopsy is NOT immediately necessary in this case given the positive CSF EBV-DNA and characteristic spectroscopy findings, though it remains the gold standard if diagnosis is uncertain 6, 7
Immediate Therapeutic Steps
Start treatment immediately with this specific regimen:
First-Line Chemotherapy
- Rituximab plus high-dose methotrexate (3 g/m²) for a median of six infusions 1, 8
- This regimen achieves median overall survival of 5.7 years and 5-year OS rate of 48% 1, 8
- A prospective trial showed 67% 5-year OS with rituximab-HD-MTX 1, 8
Concurrent Antiretroviral Therapy
- Initiate or optimize ART immediately - this is absolutely essential for immune reconstitution and contributes directly to long-term disease control 1, 8
- Effective HIV control improves tolerance to chemotherapy and overall outcomes 8, 2
- Check drug-drug interactions between chemotherapy and ART using www.hiv-druginteractions.org 6
- ART may need modification to avoid interactions, requiring multidisciplinary input 2
Supportive Care
- Provide PCP prophylaxis (trimethoprim-sulfamethoxazole or alternative) given CD4 <200 cells/µL 2, 6
- Avoid corticosteroids before tissue diagnosis if biopsy is still being considered, as they can obscure histopathology 1
Critical Pitfalls to Avoid
Do not empirically treat for toxoplasmosis in this patient - the combination of positive CSF EBV-DNA, characteristic spectroscopy pattern, and multiple lesions makes PCNSL far more likely than toxoplasmosis 6, 3
Do not use whole-brain radiotherapy as first-line treatment - it should be reserved for chemorefractory disease, patients who cannot tolerate HD-MTX, or palliative intent 8
Do not delay ART initiation - concurrent ART is mandatory and directly impacts survival, not just an adjunct 1, 8
Rituximab is not FDA/EMA approved for PCNSL, but clinical evidence strongly supports its use and it should be included 8, 6
Alternative Scenario
If this patient had well-controlled HIV on established ART (which is not the case here), consider rituximab-MTX-Ara-C-thiotepa (MATRix) or similar multi-agent induction with consolidation ASCT, as the pathogenesis would resemble immunocompetent PCNSL 1