Less invasive diagnostic tests to assist in the diagnosis have been investigated. Based on the finding that essentially 100% of HIV-related PCNSL are EBV-associated, the detection of EBV DNA by PCR amplification in the cerebrospinal fluid (CSF) has demonstrated clinical usefulness in the diagnosis, as has the use of neuroradiologic imaging to detect the malignancy. Prior studies have demonstrated that the use of a combination of neuroradiologic, immunologic, and clinical variables in the workup of focal brain lesions in HIV-infected patients to be quite accurate in identifying patients in need of brain biopsy, but a diagnostic algorithm that incorporates the combination of the most sensitive and specific tests in a timely manner has not yet been explored.