Case Report
Glioblastoma Multiforme in an HIV-Infected Patient: An Unexpected Diagnosis
Journal of the International Association of Providers of AIDS Care 2014, Vol. 13(5) 411-413 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2325957414536230 jiapac.sagepub.com
Victor Costa Morais de Oliveira, MD1, Thalita Gomes, MD2, Luiz Carlos Lima Ferreira, MD, PhD2, Ma´rcia Melo Damian, MD, PhD1, Vera Ma´rcia Fonseca Queiroz Silva, MD1, Jose´ Ribamar Arau´jo, MD1, Izabella Picinin Safe, MD1, and Rajendranath Ramasawmy, BPharm, PhD 3
Abstract We reported a case of glioblastoma multiforme in a 42-year-old female patient with HIV infection, who had a rapid progression to AIDS. She was diagnosed with an intracerebral mass and treated as neurotoxoplasmosis with improvement in the first week of therapy. On the fourth week she had a clinical worsening evolving to death, receiving the diagnosis at necropsy. Keywords glioblastoma, intracerebral mass, HIV, AIDS
Introduction Patients living with HIV are at risk of developing many complications, both infectious and noninfectious. Almost 40% to 60% of patients living with AIDS will develop neurologic disorders, and 10% of patients develop an intracerebral mass during the course of the disease.1-3 The incidence of glial central nervous system (CNS) tumors is 0.05%, while other focal masses account for up to 6%.1,2 The use of highly active antiretroviral therapy (HAART) at a higher CD4 count contributed to the reduction in opportunistic infections and a higher than expected incidence of non-AIDS–defining malignancies. Although gliomas are the most common primary CNS tumors, they are rare in patients living with AIDS and are difficult to diagnose because it often shows unusual aspects of tumor localization, growth behavior, and also presents at a younger age in the HIV-infected population. 2-4
Case Report A 42-year-old female patient living with HIV since July 2012 arrived at our emergency department in January 2013 with an altered level of consciousness. According to her family, she had no symptoms of headache, seizures, weight loss, or fever, but her level of consciousness started declining prior to about 20 days. On initial physical examination, her vital signs were stable, with a Glasgow coma score (GCS) of 9, and she displayed no signs of meningismus. Magnetic resonance imaging showed a large intracranial mass on the left frontotemporal lobe with ring enhancement after contrast, perilesional edema, outlining areas of necrosis and liquefaction (Figure 1A and B). Her CD4 count was 66 cells/mm3. Highly active antiretroviral therapy and an empiric therapy for neurotoxoplasmosis with
sulfadiazine, pyrimethamine, folinic acid, and dexamethasone for the inflammatory edema were initiated. At the end of the first week, an improvement in the level of consciousness was observed, with a steady GCS of 15 for the following 3 weeks, presenting only with hemiparesis on the right side with no loss in sensibility. In the fourth week, the patient reported difficulty in swallowing and disorientation. An emergency computed tomography scan was performed, which showed no evidence of mass reduction. In the next day, she presented with generalized tonic clonic seizure followed by apnea and hypotension. Despite the intensive care support, the patient died 2 days later. Brain tumor was confirmed on necropsy and presented as a friable grayish mass with pronounced asymmetric displacement of the hemisphere, generating cingulate gyrus and cerebellar tonsils hernia (Figure 2A). Histopathological analysis showed highly pleomorphic cells with hyperchromatic and hypertrophic nuclei, an extensive area of necrosis in addition to vascular proliferation. Immunohistochemistry performed by staining with antibody against the glial fibrillary acidic protein, a marker of glial cells, confirmed the diagnosis of glioblastoma multiforme (GBM; Figure 2B). No AIDS-defining diseases were found on necropsy. 1
Tropical Medicine Foundation Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil 2 University Hospital Getulio Vargas, Manaus, Amazonas, Brazil 3 University Nilton Lins, Manaus, Amazonas, Brazil Corresponding Author: Victor Costa Morais de Oliveira, Tropical Medicine Foundation Dr Heitor Vieira Dourado, Av Pedro Teixeira, Manaus, 69040-000, Brazil. Email: [email protected]
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Journal of the International Association of Providers of AIDS Care 13(5)
Figure 1. Magnetic resonance imaging (MRI) of (A) sagittal and (B) horizontal sections showing the intracranial mass on the left frontotemporal lobe with 4.3 6.6 5.7cm on its greatest dimensions, ring enhancement after contrast and midline shift causing compression on the left ventricle.
Figure 2. (A) Macroscopic appearance of the brain showed delineated areas of necrosis and edema generating cerebellar tonsils hernia. (B) Microscopic view with glial fibrillary acidic protein (GFAP) staining showing proliferation of glioma cells.
Discussion HIV has been shown to replicate in glial and glioma cell lines in vitro but has not been implicated in malignant cell transformation or does not any cause-and-effect relationship with brain tumors.2,4,5 The impact of the infection on immune surveillance is thought to promote the development of GBM.3 The last review of GBM cases was made in 2009 and 21 cases was described in HIV-infected patients; most of those patients were young (mean 38 years) and had a mean CD4 count of 400 cells/mm3.3 The study did not find any evidence to suggest that these patients should be treated differently from other patients with glioma, and the current recommendations include surgery followed by radiotherapy and chemotherapy (temozolomide); and prognosis is dictated by tumor progression.3,6 It is known that GBM expresses high levels of vascular endothelial growth factors (VEGFs), and the choice to use a protease inhibitor for HIV treatment may also have a benefit
as adjunctive therapy for the tumor, since in vivo they promoted the inhibition of VEGF and decreased angiogenesis.6 Despite multifocal aggressive therapy, the median survival time after diagnosis is still in the range of just 12 months.7 In the presence of an intracerebral mass in a patient living with AIDS, most protocols recommend that biopsy should be carried out if image features are atypical for neurotoxoplasmosis or when no signs of improvement are shown after 2 weeks of empirical treatment.1,2,8
Conclusion Two years prior to HIV diagnosis, our patient had donated a kidney and was negative on serologic examination, with her first positive anti-HIV test in July 2012, when she had a CD4 count of 355 cells/mm3, which declined to 66 cells/mm3 in a 6-month interval,
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demonstrating a rapid evolution to AIDS. It is presently unclear whether the tumor was a risk factor for the rapid evolution to AIDS or, conversely, whether HIV infection has contributed to a faster growth of the tumor. Still there is no evidence to support any of these hypotheses. We also illustrate the need to include primary tumors of CNS in the differential diagnosis of intracerebral mass in patients living with AIDS, particularly those not responding to the empiric treatment to neurotoxoplasmosis. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Wolff R, Zimmermann M, Marquardt G, Lanfermann H, Nafe R, Seifert V. Glioblastoma multiforme of the brain stem in a patient with aquired immunodeficiency syndrome. 2002;144(9): 941-945.
2. Buttner A, Weis S. Non-lymphomatous brain tumors in HIV-1 infection: a review. J Neurooncol. 1999;41(1):81-88. 3. Hall JR, Short SC. Management of glioblastoma multiforme in HIV patients: a case series and review of published studies. Clin Oncol. 2009;21(8):591-597. 4. Moulignier A, Mikol J, Pialoux G, Eliaszewicz M, Thurel C, Thiebaut JB. Cerebral glial tumors and human immunodeficiency virus-1 infection: more than a coincidental association. Cancer. 1994;74(2):686-692. 5. Blumenthal DT, Raizer JJ, Rosenblum MK, Bilsky MH, Hariharan S, Abrey LE. Primary intracranial neoplasms in patients with HIV. Am Acad Neurol. 1999;52(8):1648-1651. 6. Pore N, Gupta AK, Cerniglia GJ, Maity A. HIV protease inhibitors decrease VEGF/HIF-1a expression and angionesis in glioblastoma cells. Neoplasia. 2006;8(11):889-895. 7. Krex D, Klink B, Hartmann C, et al. Long-term survival with glioblastoma multiforme. Brain. 2007;130(pt 10): 2596-2606. 8. Holloway RG, Mushlin AI. Intracranial mass lesions in acquired immunodeficiency syndrome: using decision analysis to determine the effectiveness of stereotactic brain biopsy. Neurology. 1996; 46(4):1010-1015.
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on March 10, 2015
Glioblastoma Multiforme in an HIV-Infected Patient: An Unexpected Diagnosis
Journal of the International Association of Providers of AIDS Care 2014, Vol. 13(5) 411-413 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2325957414536230 jiapac.sagepub.com
Victor Costa Morais de Oliveira, MD1, Thalita Gomes, MD2, Luiz Carlos Lima Ferreira, MD, PhD2, Ma´rcia Melo Damian, MD, PhD1, Vera Ma´rcia Fonseca Queiroz Silva, MD1, Jose´ Ribamar Arau´jo, MD1, Izabella Picinin Safe, MD1, and Rajendranath Ramasawmy, BPharm, PhD 3
Abstract We reported a case of glioblastoma multiforme in a 42-year-old female patient with HIV infection, who had a rapid progression to AIDS. She was diagnosed with an intracerebral mass and treated as neurotoxoplasmosis with improvement in the first week of therapy. On the fourth week she had a clinical worsening evolving to death, receiving the diagnosis at necropsy. Keywords glioblastoma, intracerebral mass, HIV, AIDS
Introduction Patients living with HIV are at risk of developing many complications, both infectious and noninfectious. Almost 40% to 60% of patients living with AIDS will develop neurologic disorders, and 10% of patients develop an intracerebral mass during the course of the disease.1-3 The incidence of glial central nervous system (CNS) tumors is 0.05%, while other focal masses account for up to 6%.1,2 The use of highly active antiretroviral therapy (HAART) at a higher CD4 count contributed to the reduction in opportunistic infections and a higher than expected incidence of non-AIDS–defining malignancies. Although gliomas are the most common primary CNS tumors, they are rare in patients living with AIDS and are difficult to diagnose because it often shows unusual aspects of tumor localization, growth behavior, and also presents at a younger age in the HIV-infected population. 2-4
Case Report A 42-year-old female patient living with HIV since July 2012 arrived at our emergency department in January 2013 with an altered level of consciousness. According to her family, she had no symptoms of headache, seizures, weight loss, or fever, but her level of consciousness started declining prior to about 20 days. On initial physical examination, her vital signs were stable, with a Glasgow coma score (GCS) of 9, and she displayed no signs of meningismus. Magnetic resonance imaging showed a large intracranial mass on the left frontotemporal lobe with ring enhancement after contrast, perilesional edema, outlining areas of necrosis and liquefaction (Figure 1A and B). Her CD4 count was 66 cells/mm3. Highly active antiretroviral therapy and an empiric therapy for neurotoxoplasmosis with
sulfadiazine, pyrimethamine, folinic acid, and dexamethasone for the inflammatory edema were initiated. At the end of the first week, an improvement in the level of consciousness was observed, with a steady GCS of 15 for the following 3 weeks, presenting only with hemiparesis on the right side with no loss in sensibility. In the fourth week, the patient reported difficulty in swallowing and disorientation. An emergency computed tomography scan was performed, which showed no evidence of mass reduction. In the next day, she presented with generalized tonic clonic seizure followed by apnea and hypotension. Despite the intensive care support, the patient died 2 days later. Brain tumor was confirmed on necropsy and presented as a friable grayish mass with pronounced asymmetric displacement of the hemisphere, generating cingulate gyrus and cerebellar tonsils hernia (Figure 2A). Histopathological analysis showed highly pleomorphic cells with hyperchromatic and hypertrophic nuclei, an extensive area of necrosis in addition to vascular proliferation. Immunohistochemistry performed by staining with antibody against the glial fibrillary acidic protein, a marker of glial cells, confirmed the diagnosis of glioblastoma multiforme (GBM; Figure 2B). No AIDS-defining diseases were found on necropsy. 1
Tropical Medicine Foundation Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil 2 University Hospital Getulio Vargas, Manaus, Amazonas, Brazil 3 University Nilton Lins, Manaus, Amazonas, Brazil Corresponding Author: Victor Costa Morais de Oliveira, Tropical Medicine Foundation Dr Heitor Vieira Dourado, Av Pedro Teixeira, Manaus, 69040-000, Brazil. Email: [email protected]
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on March 10, 2015
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Journal of the International Association of Providers of AIDS Care 13(5)
Figure 1. Magnetic resonance imaging (MRI) of (A) sagittal and (B) horizontal sections showing the intracranial mass on the left frontotemporal lobe with 4.3 6.6 5.7cm on its greatest dimensions, ring enhancement after contrast and midline shift causing compression on the left ventricle.
Figure 2. (A) Macroscopic appearance of the brain showed delineated areas of necrosis and edema generating cerebellar tonsils hernia. (B) Microscopic view with glial fibrillary acidic protein (GFAP) staining showing proliferation of glioma cells.
Discussion HIV has been shown to replicate in glial and glioma cell lines in vitro but has not been implicated in malignant cell transformation or does not any cause-and-effect relationship with brain tumors.2,4,5 The impact of the infection on immune surveillance is thought to promote the development of GBM.3 The last review of GBM cases was made in 2009 and 21 cases was described in HIV-infected patients; most of those patients were young (mean 38 years) and had a mean CD4 count of 400 cells/mm3.3 The study did not find any evidence to suggest that these patients should be treated differently from other patients with glioma, and the current recommendations include surgery followed by radiotherapy and chemotherapy (temozolomide); and prognosis is dictated by tumor progression.3,6 It is known that GBM expresses high levels of vascular endothelial growth factors (VEGFs), and the choice to use a protease inhibitor for HIV treatment may also have a benefit
as adjunctive therapy for the tumor, since in vivo they promoted the inhibition of VEGF and decreased angiogenesis.6 Despite multifocal aggressive therapy, the median survival time after diagnosis is still in the range of just 12 months.7 In the presence of an intracerebral mass in a patient living with AIDS, most protocols recommend that biopsy should be carried out if image features are atypical for neurotoxoplasmosis or when no signs of improvement are shown after 2 weeks of empirical treatment.1,2,8
Conclusion Two years prior to HIV diagnosis, our patient had donated a kidney and was negative on serologic examination, with her first positive anti-HIV test in July 2012, when she had a CD4 count of 355 cells/mm3, which declined to 66 cells/mm3 in a 6-month interval,
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on March 10, 2015
Oliveira et al
413
demonstrating a rapid evolution to AIDS. It is presently unclear whether the tumor was a risk factor for the rapid evolution to AIDS or, conversely, whether HIV infection has contributed to a faster growth of the tumor. Still there is no evidence to support any of these hypotheses. We also illustrate the need to include primary tumors of CNS in the differential diagnosis of intracerebral mass in patients living with AIDS, particularly those not responding to the empiric treatment to neurotoxoplasmosis. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Wolff R, Zimmermann M, Marquardt G, Lanfermann H, Nafe R, Seifert V. Glioblastoma multiforme of the brain stem in a patient with aquired immunodeficiency syndrome. 2002;144(9): 941-945.
2. Buttner A, Weis S. Non-lymphomatous brain tumors in HIV-1 infection: a review. J Neurooncol. 1999;41(1):81-88. 3. Hall JR, Short SC. Management of glioblastoma multiforme in HIV patients: a case series and review of published studies. Clin Oncol. 2009;21(8):591-597. 4. Moulignier A, Mikol J, Pialoux G, Eliaszewicz M, Thurel C, Thiebaut JB. Cerebral glial tumors and human immunodeficiency virus-1 infection: more than a coincidental association. Cancer. 1994;74(2):686-692. 5. Blumenthal DT, Raizer JJ, Rosenblum MK, Bilsky MH, Hariharan S, Abrey LE. Primary intracranial neoplasms in patients with HIV. Am Acad Neurol. 1999;52(8):1648-1651. 6. Pore N, Gupta AK, Cerniglia GJ, Maity A. HIV protease inhibitors decrease VEGF/HIF-1a expression and angionesis in glioblastoma cells. Neoplasia. 2006;8(11):889-895. 7. Krex D, Klink B, Hartmann C, et al. Long-term survival with glioblastoma multiforme. Brain. 2007;130(pt 10): 2596-2606. 8. Holloway RG, Mushlin AI. Intracranial mass lesions in acquired immunodeficiency syndrome: using decision analysis to determine the effectiveness of stereotactic brain biopsy. Neurology. 1996; 46(4):1010-1015.
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on March 10, 2015
