Evaluation of Brain Lesions in HIV-infected Patients for Diagnosis of Primary Central Nervous System Lymphoma

This study will evaluate the usefulness of two tests in quickly distinguishing whether a patient with HIV infection and focal brain lesions (an injury in a specific area of the brain) has a rare type of cancer called primary central nervous system lymphoma (PCNSL), or a parasitic infection called toxoplasmic encephalitis. Toxoplasmic encephalitis is caused by a parasite and can be treated with antibiotics. PCNSL (lymphoma of the brain or spinal cord) must be definitively diagnosed with a brain biopsy (removal of a small piece of brain tissue), and the treatment is radiation therapy and chemotherapy. The tests under study for diagnosing PCNSL or toxoplasmic encephalitis are measurement of Epstein Barr virus (EBV) DNA in cerebrospinal fluid (CSF) and FDG-PET scan of the brain. EBV is often found in the CSF of people with PCNSL. The study also will compare the accuracy of two imaging techniques-TI-SPECT and FDG-PET-in distinguishing between toxoplasmosis and PCNSL. Patients 18 years of age and older who have HIV infection and at least one focal brain lesion without a prior history of PCNSL or toxoplasmic encephalitis may be eligible for this study. Each candidate is screened with a medical history, physical examination, blood and urine tests and MRI scans of the brain. Upon entering the study, all participants take medication to treat toxoplasmic encephalitis. They undergo lumbar puncture (spinal tap) to obtain CSF for analysis, an FDG-PET scan, and a 201TI-SPECT scan. For the PET scan, a radioactive substance is injected into an arm, followed by scanning in a doughnut-shaped machine similar to a CT scanner. SPECT is similar to PET but uses a different radioactive tracer, and the patient lies on a table while the SPECT camera rotates around the patient's head. Patients whose test results indicate a low risk for lymphoma continue antibiotic therapy for toxoplasmosis. They have repeat MRI scans around 4, 7, and 14 days after starting the drug to monitor the response to therapy. Antiretroviral therapy is initiated in patients who are not already on such a regimen. Patients whose test results indicate a high risk for PCNSL have a CT scan to look for evidence of lymphoma elsewhere in the body and are referred for consultation with a neurosurgeon to discuss undergoing a brain biopsy. The brain biopsy is done in the operating room under general anesthesia. A small cut is made in the scalp and a small opening is made in the skull over the area of the brain to be biopsied. A needle is placed in the opening in the skull and, guided by CT or MRI, moved to the abnormal area of the brain, where a small piece of tissue is removed for study under a microscope. Patients found to have toxoplasmosis are discharged from the hospital to the care of their primary care physician after they are getting better and are tolerating all their medications. They return to NIH for follow-up visits about 4 weeks, and 6 months after discharge. Patients found to have lymphoma are referred to the National Cancer Institute for screening for enrollment in a treatment protocol. Patients who are not eligible for a treatment protocol are referred back to their primary care physician or for another NIH treatment protocol, if one is available. Patients with lymphoma are seen at the NIAID outpatient clinic for follow-up visits and laboratory examinations every 3 months for 2 years.

Sex

All

Minimum age

18 Years

* INCLUSION CRITERIA:

Adult (18 years old or older) HIV-infected patient

HIV infected by OraQuick rapid test using saliva, venipuncture whole blood, or fingerstick whole blood; or by reactive ELISA and Western Blot as determined by an outside CLIA-approved laboratory facility or by NIH Clinical Pathology Laboratory or SAIC-Frederick Inc Monitoring Laboratory. HIV infection as determined by an outside CLIA-approved laboratory facility will be verified by a standard HIV-1 ELISA with Western Blot confirmation prior to brain biopsy.

Evidence of contrast-enhancing focal brain lesion(s) as seen on MRI or CT

Willingness to give informed consent and provided by Durable Power of Attorney. In the event that no Durable Power of Attorney has been designated and the patient is unable to do so, the NIH Ethics Committee will be consulted. All patients must designate a Durable Power of Attorney in order to participate in the study.

Willingness to undergo the procedures involved in the diagnostic evaluation: lumbar puncture, FDG-PET scan, 201Tl-SPECT scan, and brain biopsy.

Permit the storage of blood, CSF, and tissue samples for future research use

Willingness to undergo HLA testing

EXCLUSION CRITERIA:

Previous PCNSL

History of prior malignancy other than PCNSL unless in remission for 1 year or longer; non-melanoma skin cancer and Kaposi's sarcoma excepted

History of previous diagnosis of toxoplasmic encephalitis or other CNS infection causing focal contrast-enhancing brain lesions

Pregnancy or currently breast feeding

Have any other condition that the research team considers a contraindication to participating in the study, e.g. severe cardiac, renal, or pulmonary dysfunction.

Weight greater than 400 lb for PET and 500 lb for SPECT (limit of the gantry).

• BACKGROUNDCote TR, Manns A, Hardy CR, Yellin FJ, Hartge P. Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/Cancer Study Group. J Natl Cancer Inst. 1996 May 15;88(10):675-9. doi: 10.1093/jnci/88.10.675. PMID 8627644
• BACKGROUNDBasso U, Brandes AA. Diagnostic advances and new trends for the treatment of primary central nervous system lymphoma. Eur J Cancer. 2002 Jul;38(10):1298-312. doi: 10.1016/s0959-8049(02)00031-x. PMID 12091059
• BACKGROUNDMacMahon EM, Glass JD, Hayward SD, Mann RB, Becker PS, Charache P, McArthur JC, Ambinder RF. Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet. 1991 Oct 19;338(8773):969-73. doi: 10.1016/0140-6736(91)91837-k. PMID 1681341