A 31-year-old man presented to the emergency department in December 2016 with new-onset tonic-clonic seizures, on a background of 19 kg weight loss, progressive lethargy and cognitive decline over the preceding 18 months. He had travelled extensively across the African subcontinent whilst working aboard a ship and during this time had engaged in unprotected intercourse with female sex workers.
Salient examination findings included nystagmus on right-lateral gaze, past-pointing in the left upper limb, brisk reflexes and an unsteady gait, suggestive of underlying cerebellar pathology. Following biochemical and serological investigations, the patient was diagnosed with HIV-1, with a viral load of 1 243 938 copies/mL and a CD4 lymphocyte count of 12 cells/microL. Initial computed tomography (CT) imaging revealed multiple lesions in the brainstem, cerebellum, basal ganglia and both cerebral hemispheres, with significant local mass effect and effacement of the left lateral ventricle. Magnetic resonance imaging (MRI) of the brain was also undertaken at this time, which demonstrated multiple ring-enhancing lesions (Figure 1). Mediastinal and hilar lymph node enlargement identified on CT imaging of the chest, abdomen and pelvis was felt to be in keeping with persistent generalised lymphadenopathy (PGL) because of advanced HIV as there was no palpable cervical, axillary or inguinal lymphadenopathy (Figure 2).
The patient was commenced on treatment for presumptive toxoplasmosis, with sulfadiazine/pyramethamine/folinic acid and adjunctive high-dose dexamethasone, levetiracetam. He also simultaneously commenced antiretroviral therapy (ART) comprising of tenofovir/emtricitabine and dolutegravir, along with prophylactic antibiotics and antifungals against opportunistic infections. Blood cultures were negative as was toxoplasma serum Immunoglobulin G (IgG). Tuberculosis with CNS involvement and cryptococcoma were considered as differential diagnoses; however, cryptococcal antigen was negative as subsequently were mycobacterial blood and induced sputum cultures. Cerebrospinal fluid examination was not attempted in light of the cerebellar lesions.
Following 2 weeks of toxoplasmosis treatment, there was no improvement in the appearances of the intra-cranial lesions on repeat MR brain imaging, with two new lesions being identified (Figure 3). At this point, alternative diagnoses such as systemic lymphoma with intra-cranial metastases and PCNSL were pursued over toxoplasmosis. A fluodeoxyglucose positron-emission tomography (FDG-PET-CT) and brain biopsy were, thus, arranged with the aim of obtaining a more definitive diagnosis.
FDG-PET-CT was undertaken 3 weeks following initial presentation and demonstrated high avidity activity only in the brain including the right parietal, right parieto-occipital and left frontal regions as well as the cerebellum and basal ganglia (standardised uptake value [SUV] max 7.3 compared with normal brain cortex). No FDG-avid mediastinal lymph nodes were identified and these appearances pointed towards the diagnosis of PCNSL, rather than systemic lymphoma with cerebral metastases.
The right parietal lobe brain biopsy demonstrated a suspicious lymphoid infiltrate. Mycobacterial and fungal stains were negative as was immunostaining for herpes simplex virus (HSV1), HSV2, cytomegalovirus (CMV) and John Cunningham virus (JCV). Epstein-Barr encoding region (EBER) in situ hybridisation staining was also negative; however, this was a likely false negative result, in the context of necrosis and ribonucleic acid (RNA) degradation. Within the necrotic areas, the cellular outlines and remains were strongly positive for CD20, CD79a and BCL2. They were negative for CD19, CD3, CD5, CD10, BCL6 and PAX5. Final histopathology results were in keeping with a high-grade B-cell lymphoma that was necrotic.
The patient was commenced on MATRix chemotherapy (rituximab, methotrexate, cytarabine, with omission of thioTEPA for the first two cycles) for HIV-associated primary cerebral lymphoma. Within 8 weeks of commencement of highly active antiretroviral therapy (HAART), there was a 3log10 fold decrease in HIV-1 viral load. There has also been a marked improvement in cognitive function and gait following four cycles of MATRix chemotherapy (Figure 4).
Repeat MRI imaging 6 months following initial presentation also demonstrates a reduction in volume of the supra and infra-tentorial parenchymal and sub-ependymal lesions, with improvement in the degree of peri-lesional vasogenic oedema, in keeping with a positive disease response (Figure 5). The patient continues to make good progress and is currently being worked up for consolidative therapy with an autologous stem cell transplantation.