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Central Nervous System Lymphoma in HIV Workup

  • Author: Florian P Thomas, MD, PhD, Drmed, MA, MS; Chief Editor: Niranjan N Singh, MD, DM  more...
 
Updated: Dec 28, 2015
 

Overview

Almost 100% of affected patients exhibit evidence of Epstein-Barr virus (EBV) in the CSF and lymphomatous lesions. The development of HIV-associated CNS lymphoma is typically associated with a CD4+ lymphocyte count below 100 cells/mL. Chest radiography and an abdominal ultrasound may be indicated to rule out systemic lymphoma as the underlying cause.

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CSF Analysis

CSF analysis in patients with CNS lymphoma shows pleocytosis and elevated protein. Cytologic results are positive for monoclonal malignant-appearing lymphocytes.

Amplification of EBV deoxyribonucleic acid (DNA) in CSF using the polymerase chain reaction (PCR) corroborates the diagnosis of primary CNS lymphoma. However, the declining incidence of CNS lymphoma may be diminishing the specificity of this finding.[10] Quantitative PCR may increase specificity: Corcoran et al found that using a cut-off of 10,000 EBV DNA copies/mL improved the specificity and positive predictive value when compared with a qualitative result for the diagnosis of CNS lymphoma (96% vs 66%, and 50% vs 10%, respectively).[11] The EBV DNA in the CSF has a low positive predictive value (10-50%) when used in isolation as a positive marker because elevated EBV DNA is also seen in patients with HIV without primary CNS lymphoma.

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Brain Imaging

On computed tomography scans, a hypodense or hyperdense lesion that enhances in a nodular, homogeneous, or ringlike pattern may be observed. Significant edema and mass effect may be present. (See the image below.)

On CT scan, cerebral lymphoma appears as focal les On CT scan, cerebral lymphoma appears as focal lesions with nodular ring enhancement, mass effect, and surrounding edema. Common sites include the periventricular white and gray matter and cerebellum.

Multiple lesions can occur, although less frequently than with toxoplasmosis. Magnetic resonance imaging (MRI) may reveal additional lesions.

A thallium-201 single-photon emission computed tomography (201 TI SPECT) scan may be useful in distinguishing between lymphoma and toxoplasmosis. Increased201 Tl uptake co-localizing with the lesion on MRI is highly specific for primary CNS lymphoma.

Tumor size of at least 2 cm increases the diagnostic yield. Positive results need to be confirmed by biopsy of the identified lesion.

An 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) scan study has a predictive value similar to that of201 TI SPECT.

MR spectroscopy in primary CNS lymphoma typically shows decreased N -acetylaspartate and creatine, increased choline (suggesting a tumoral cell proliferation), and at-baseline lipid-lactate peaks reflecting necrosis, which is a common feature of primary CNS lymphoma.

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Brain Biopsy

Definitive diagnosis requires stereotactic brain biopsy, usually after a therapeutic trial for cerebral toxoplasmosis. Histologic findings in CNS lymphoma vary and consist of a small, noncleaved type and a large, immunoblastic type. (See the image below.)

Light microscopic examination of primary CNS lymph Light microscopic examination of primary CNS lymphoma is characterized by dense infiltrates of large lymphocytes with irregular nuclei. The tumor cells can display a prominent vasocentric pattern and infiltrate blood vessel walls. Areas of necrosis may be present. Contributed by Dr Beth Levy, Saint Louis University School of Medicine, St Louis, Missouri.
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Contributor Information and Disclosures
Author

Florian P Thomas, MD, PhD, Drmed, MA, MS Director, National MS Society Multiple Sclerosis Center; Professor and Director, Clinical Research Unit, Department of Neurology, Adjunct Professor of Physical Therapy, Associate Professor, Institute for Molecular Virology, St Louis University School of Medicine; Editor-in-Chief, Journal of Spinal Cord Medicine

Florian P Thomas, MD, PhD, Drmed, MA, MS is a member of the following medical societies: Academy of Spinal Cord Injury Professionals, American Academy of Neurology, American Neurological Association, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Niranjan N Singh, MD, DM Associate Professor of Neurology, University of Missouri-Columbia School of Medicine

Niranjan N Singh, MD, DM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

References
  1. Maher EA, Fine HA. Primary CNS lymphoma. Semin Oncol. 1999 Jun. 26(3):346-56. [Medline].

  2. Gasser O, Bihl FK, Wolbers M, et al. HIV patients developing primary CNS lymphoma lack EBV-specific CD4+ T cell function irrespective of absolute CD4+ T cell counts. PLoS Med. 2007 Mar 27. 4(3):e96. [Medline]. [Full Text].

  3. Wolf T, Brodt HR, Fichtlscherer S. Changing incidence and prognostic factors of survival in AIDS-related non-Hodgkin's lymphoma in the era of highly active antiretroviral therapy (HAART). Leuk Lymphoma. 2005 Feb. 46(2):207-15. [Medline].

  4. Haldorsen IS, Krakenes J, Goplen AK, Dunlop O, Mella O, Espeland A. AIDS-related primary central nervous system lymphoma: a Norwegian national survey 1989-2003. BMC Cancer. 2008 Aug 6. 8:225. [Medline]. [Full Text].

  5. Bayraktar S, Bayraktar UD, Ramos JC, Stefanovic A, Lossos IS. Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors. J Neurooncol. 2011 Jan. 101 (2):257-65. [Medline].

  6. Matinella A, Lanzafame M, Bonometti MA, Gajofatto A, Concia E, Vento S, et al. Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study. J Neurol. 2015 May. 262 (5):1317-27. [Medline].

  7. Bossolasco S, Falk KI, Ponzoni M, et al. Ganciclovir is associated with low or undetectable Epstein-Barr virus DNA load in cerebrospinal fluid of patients with HIV-related primary central nervous system lymphoma. Clin Infect Dis. 2006 Feb 15. 42(4):e21-5. [Medline].

  8. Biggar RJ, Engels EA, Ly S. Survival after cancer diagnosis in persons with AIDS. J Acquir Immune Defic Syndr. 2005 Jul 1. 39(3):293-9. [Medline].

  9. Skiest DJ, Crosby C. Survival is prolonged by highly active antiretroviral therapy in AIDS patients with primary central nervous system lymphoma. AIDS. 2003 Aug 15. 17(12):1787-93. [Medline].

  10. Ambinder RF, Bhatia K, Martinez-Maza O, Mitsuyasu R. Cancer biomarkers in HIV patients. Curr Opin HIV AIDS. 2010 Nov. 5(6):531-7. [Medline]. [Full Text].

  11. Corcoran C, Rebe K, van der Plas H, Myer L, Hardie DR. The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons. J Clin Virol. 2008 Aug. 42(4):433-6. [Medline].

  12. Nagai H, Odawara T, Ajisawa A, Tanuma J, Hagiwara S, Watanabe T, et al. Whole brain radiation alone produces favourable outcomes for AIDS-related primary central nervous system lymphoma in the HAART era. Eur J Haematol. 2010 Jun. 84(6):499-505. [Medline].

  13. Bossolasco S, Falk KI, Ponzoni M. Ganciclovir is associated with low or undetectable Epstein-Barr virus DNA load in cerebrospinal fluid of patients with HIV-related primary central nervous system lymphoma. Clin Infect Dis. 2006 Feb 15. 42(4):e21-5. [Medline].

  14. Aboulafia DM, Ratner L, Miles SA. Antiviral and immunomodulatory treatment for AIDS-related primary central nervous system lymphoma: AIDS Malignancies Consortium pilot study 019. Clin Lymphoma Myeloma. 2006 Mar. 6(5):399-402. [Medline].

 
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On CT scan, cerebral lymphoma appears as focal lesions with nodular ring enhancement, mass effect, and surrounding edema. Common sites include the periventricular white and gray matter and cerebellum.
Light microscopic examination of primary CNS lymphoma is characterized by dense infiltrates of large lymphocytes with irregular nuclei. The tumor cells can display a prominent vasocentric pattern and infiltrate blood vessel walls. Areas of necrosis may be present. Contributed by Dr Beth Levy, Saint Louis University School of Medicine, St Louis, Missouri.
 
 
 
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