A 25-year-old man is brought to the emergency department due to a generalized tonic-clonic seizure. According to his roommate, the patient has had worsening confusion and lethargy for the last 2 weeks. Today, he had a seizure lasting approximately 3 minutes. The patient has a history of HIV and is not adherent with antiretroviral therapy or other HIV-related medications. He is an active injection drug user. Temperature is 37.7 C (99.9 F), blood pressure is 130/80 mm Hg, pulse is 98/min, and respirations are 16/min. On physical examination, the patient is somnolent but arousable. There is no focal extremity weakness or sensory loss. CD4 count is 26/mm³ and viral load is 86,000 copies/mL. MRI of the brain with contrast shows a solitary, irregular, nonhomogenous ring-enhancing lesion in the periventricular area. Cerebrospinal fluid PCR is positive for Epstein-Barr virus DNA. Which of the following is the most likely diagnosis in this patient?

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11ec25c8_d47f_b980_bc81_077a1f30be9c_MD0003_00 This patient with untreated AIDS has confusion, seizure, and a ring-enhancing lesion on brain MRI. Although cerebral toxoplasmosis and bacterial abscess can cause similar manifestations, the presence of Epstein-Barr virus (EBV) DNA in the cerebrospinal fluid makes primary CNS lymphoma (PCNSL) most likely. Patients with AIDS are at increased risk for malignancy due to impaired immunosurveillance and unchecked expression of latent viral oncogenes. AIDS-defining malignancies are associated with latent viral infection: Kaposi sarcoma is associated with human herpesvirus 8, invasive cervical cancer is associated with human papillomavirus, and non-Hodgkin lymphoma and PCNSL are associated with EBV. Therefore, evaluation for viral components is often part of the diagnostic workup for these malignancies. Suspicion for PCNSL is generally raised when a patient with AIDS develops progressive confusion, lethargy, seizure, and/or focal neurologic deficits in the setting of a solitary, irregular, nonhomogenous ring-enhancing lesion on brain MRI. The diagnosis is generally confirmed when EBV DNA is isolated in the cerebrospinal fluid (specificity of ~100% for PCNSL). Brain biopsy is not usually required. (Choice A) AIDS dementia complex is marked by cortical and subcortical atrophy and ventricular enlargement on brain imaging. Patients usually have subacute or chronic cognitive deficits, depressive symptoms, and impaired psychomotor ability. (Choice B) Bacterial brain abscess is much less common in patients with advanced AIDS than cerebral toxoplasmosis or PCNSL. Most cases are associated with signs and symptoms of primary infection in other areas (eg, dental infection); EBV DNA would not be seen in the cerebrospinal fluid. (Choice C) Cerebral toxoplasmosis is common in patients with advanced AIDS (CD4 count <50/mm³). However, multiple ring-enhancing lesions are usually present, and EBV DNA is not seen in the cerebrospinal fluid. (Choice E) Progressive multifocal leukoencephalopathy commonly occurs in patients with advanced AIDS. Although this type of leukoencephalopathy often presents with confusion, lethargy, and seizure, brain imaging demonstrates numerous nonenhancing lesions that do not cause mass effect. In addition, this condition is associated with the reactivation of JC virus, not EBV. Educational objective: Patients with advanced AIDS are at increased risk for malignancy. Primary CNS lymphoma is an AIDS-defining malignancy associated with the expression of Epstein-Barr virus oncogenes, which can often be identified in the cerebrospinal fluid. MRI of the brain generally shows a solitary, irregular, nonhomogenous ring-enhancing mass.

A 25-Year-Old Man Is Brought to the Emergency Department Due