PCNSL is a rare malignancy that affects the brain, leptomeninges, spinal cord or orbits. It is greatly increased in the PWLH compared to the general population, especially with CD4 < 100 cm/mm3 and is considered an AIDS defining illness. Overall incidence has reduced substantially in the post cART era however, unlike other HIV-associated lymphomas, PCNSL continues to have consistently worse outcomes in PLWH than the general population in spite of widespread use of cART ​(59)​. Epstein-Barr virus is highly associated with the condition and is theorised to play a direct role in oncogenesis via immune dysregulation, expression of oncogenic proteins, dysregulated apoptosis and increased lymphocyte proliferation ​(60)​.  

PCNSL usually occurs in the brain with either solitary or less commonly multiple supratentorial lesions but can also affect the spinal cord. Clinical features include headache, constitutional symptoms (fevers, night sweats, malaise), weight loss seizures and specific neurological syndromes dependent on the site of the lesions ​(60)​. MRI demonstrates T2 contrast enhancing lesions. CSF typically demonstrates elevated protein, lymphocytic pleocytosis, low glucose and positive CSF EBV PCR ​(60)​.  Diagnosis is established with CSF cytology, flow cytometry and histopathology of biopsy of lesions. Outcomes are unfortunately poor in PCNSL in PLWH with a 5 year survival of 14% ​(59)​. Treatment regimens involve a combination of steroid therapy, high dose methotrexate and radiotherapy ​(60)​.