Neurological Research A Journal of Progress in Neurosurgery, Neurology and Neurosciences ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20 Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: An interesting case O.A. Harris, S.D. Chang, B.T. Harris & J.R. Adler To cite this article: O.A. Harris, S.D. Chang, B.T. Harris & J.R. Adler (2000) Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: An interesting case, Neurological Research, 22:5, 473-477, DOI: 10.1080/01616412.2000.11740703 To link to this article: http://dx.doi.org/10.1080/01616412.2000.11740703 Published online: 21 Jul 2016. Submit your article to this journal Article views: 11 View related articles Citing articles: 9 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Columbia University Libraries] Date: 15 August 2017, At: 08:43 Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: An interesting case Odette A. Harris, Steven D. Chang, Brent T. Harris* and John R. Adler Downloaded by [Columbia University Libraries] at 08:43 15 August 2017 Department of Neurosurgery, *Department of Neuropathology, Stanford University School of Medicine, Stanford, CA, USA High grade gliomas foster an environment rich in angiogenic factors that promote neovascularity. We report a case of a cerebral arteriovenous malformation, which developed in the setting of a high grade astrocytoma. The patient presented with complaints of confusion and left hemiparesis. An initial cerebral angiogram was normal. Repeat angiography six weeks later demonstrated an extremely vascular lesion with arteriovenous shunting involving the right thalamus and occipital lobe. Histopathologic evaluation of open biopsy and autopsy specimens demonstrated a high grade astrocytoma in association with an arteriovenous malformation. Immunohistochemical staining with VEGF was diffusely positive. A possible role for the hyperangiogenic environment of a high grade astrocytoma resulting in the development of an arteriovenous malformation is discussed. [Neural Res 2000; 22: 473-477] Keyword: Angiogenesis; astrocytoma; A VM; glioma; tumor INTRODUCTION The rare association between high grade astrocytomas and cerebral arteriovenous malformations (AVM) has been previously reported 1- 3 . These reports describe either the development of a glioma in the setting of a known AVM or simultaneous recognition of the two lesions. Although a hyperangiogenic environment has been identified as a key component in the genesis of both intracranial lesions, a solid understanding of the codevelopment of these lesions is lacking. We report a patient in whom a de novo AVM developed in association with or subsequent to a high grade glioma, a previously unreported occurrence. The histopathology in this case also highlights the potential role of a hypervascular environment in the initiation and development of an A VM. CASE REPORT A 57 -year-old man presented with a two-month history of headaches, mild confusion, left sided weakness and numbness. Computed tomography (CT) of the brain was negative. Carotid Doppler demonstrated complete occlusion of the left and 60% stenosis of the right internal carotid artery. These findings were confirmed by carotid angiogram, at which time a cerebral angiogram was normal (Figure 7A, B). The patient subsequently underwent right carotid endarterectomy as treatment for his right carotid stenosis. Despite surgery, his symptoms progressed and he developed intermittent nausea, vomiting and a 9 kg weight loss. Repeat head CT three Correspondence and reprint requests to: John R. Adler, MD, Department of Neurosurgery, Stanford University Medical Center, 300 Pasteur Drive, Edwards Building, Stanford, CA 94305, USA. Accepted for publication December 1999. © 2000 Forefront Publishing Group 0161-6412/00/050473-05 weeks after endarterectomy demonstrated low density in the right thalamus. A contrast MRI revealed a 5.0x6.0 x4.5 em heterogeneously enhancing hypervascular mass in the right thalamus, midbrain and medial occipital lobe, and the patient was referred for diagnosis and management. Repeat cerebral angiography two months after the initial study revealed an extremely vascular lesion with arteriovenous shunting, located within the right thalamus, medial temporal and occipital lobes (Figure 7C, O). A contrast MRI was repeated (Figure 2) and confirmed the presence of an enhancing hypervascular mass as earlier described. The lesion was approached intrahemisphericall y using an occipital craniotomy. Gross inspection revealed what appeared to be an AVM, which was judged to be unresectable. A small amount of gliotic-like brain immediatel y adjacent to this vascular lesion was biopsied, and the histopathologic findings were consistent with a malignant astrocytic neoplasm. Following an unremarkalbe post-operative course, the patient began radiation therapy. However his condition deteriorated and he died four months after surgery. An autopsy of the brain was performed. PATHOLOGY Histopathologic review of the biopsy and autopsied brain revealed a highly malignant astrocytic neoplasm localized in the right inferior temporal/occipital lobes extending into the brain stem and cerebellum with extensive leptomeningeal spread (Figure 3A). This fibrillary tumor was composed of enlarged, oblong cells with pleomorphic, hyperchromatic nuclei (Figure 38) . Occasional mitotic figures were observed. The tumor was intimately enmeshed with large arterial and venous Neurological Research, 2000, Volume 22, j uly 473 Downloaded by [Columbia University Libraries] at 08:43 15 August 2017 Acquired cerebral A VM induced by astrocytoma: Odette A. Harris et al. Figure 1: A,B: Initial right carotid angiogram showing A: lateral and 8: anterior-posterior views. C,D: Right carotid angiogram six weeks subsequent to the first, showing an arteriovenous malformation in C: lateral and 0: anterior-posterior views channels. Elastic van Gieson (EVG) staining highlighted the internal elastica of the arterial component, which was incomplete and reduplicated in many places (Figure 3C). Such features are characteristic of arteriovenous malformations 4 . Immunohistochemical studies demonstrate tumor cells with positive GFAP (glial fibrillary acid protein, DAKO) (not shown) and VEGF immunoreactivity (vascular endothelial growth factor, Santa Cruz Biochemical, Santa Cruz, CA, USA) (Figure 30). The VEGF 474 Neurological Research, 2000, Volume 22, july immunoreactivity was cytoplasmic and observed with greatest intensity in tumor cells surrounding vessels. DISCUSSION An association between AVM and glioma has been previously described 1- 3 . However, in all these reports the arteriovenous malformation either preceded the development of the glioma or the two lesions were first identified simultaneously. What makes this case so Downloaded by [Columbia University Libraries] at 08:43 15 August 2017 Acquired cerebral A VM induced by astrocytoma: Odette A Harris et al. Figure 2: MRI of the brain, axial and coronal post-contrast images unique is the de novo angiographic appearance of an AVM, a previously unreported observation. Goodkin et a/. 5, in their review of the literature, explored the question of whether these lesions were coexistent or sequential. Of 14 cases, none described an A VM developing after the identification of a glioma. In contrast, acquired AVMs have been reported in nonneoplastic settings. Examples include the development of an AVM following a cerebral infarct6 or at the site of a previously resected lesion with a normal post-operative angiogram 7. In such cases the theories regarding the etiology of an acquired AVM focus on an environment of enhanced angiogenesis 6,7. Gliomas are currently believed to arise as a result of multiple unique combinations of genetic aberration, including the loss of tumor suppressor genes and amplification of angiogenic factors 8- 12 . Meanwhile, cerebral A VMs are thought to arise from congenital failure of capillary development during gestation, resulting in a direct communication between arteries and veins 13 . Neovascularization, the formation of blood vessels de novo, and angiogenesis, the process of new vessel formation from pre-existing vasculature, are critical steps for the development of both A VMs and glial tumors. Within the latter, it is reasonable to speculate that local angiogenic factors could potentially contribute to the development of a vascular malformation. The process of angiogenesis and the role of angiogenic factors in the pathogenesis of central nervous system vascular malformations and malignancies have been a focus of several studies in recent years. Causative factors identified to date include basic fibroblast growth factor (bFGF), angiogenin, tumor necrosis factor rx, vascular endothelial growth factor (VEGF) and a number of structural and matrix vascular wall proteins 8- 10,12,14 . VEGF, also known as vascular permeability factor (VPF), is a cytokine with numerous functions including induction of angiogenesis and microvascular hyperpermeability15. Multiple studies have established an association between angiogenesis and microvascular permeability to upregulated levels of VEGF in various tissues and settings, including several human tumors. VEGF appears to be a major factor in the neovascularization and growth of high grade gliomas 8' 12,15- 18. In particular, tissue hypoxia results in the upregulation of VEGF mRNA and protein levels 16, and according to Shweiki et a/. 16 may be the mechanism for triggering angiogenesis in high grade gliomas. Because VEGF is specific for vascular endothelium and is shown to be an endothelial cell mitogen both in vitro and in vivo15, it is thought to play a pivotal role in the initiation of angiogenesis and AVM growth 7. In the previously reported cases of acquired cerebral AVM, a hyperangiogenic environment characterized the pathology6'7. Sonstein et aJ.l identified increased focal cellular VEGF staining within a population of recurrent AVMs, patients theorized to be undergoing active angiogenesis. Their conclusion was that VEGF, in concert with other processes, played an integral role in AVM development. Although the specific stimuli for angiogenesis are as yet unidentified, it is clear that VEGF plays a key and necessary role. Numerous studies have concluded that VEGF is common to both high grade astrocytomas Neurological Research, 2000, Volume 22, j uly 475 Downloaded by [Columbia University Libraries] at 08:43 15 August 2017 Acquired cerebral A VM induced by astrocytoma: Odette A Harris et al. Figure 3: Arteriovenous malformation (AVM) associated with anaplastic astrocytoma. A: Enlarged and dilated arterial and venous channels course through leptomeninges filled with neoplastic cells (original magnification x 100). 8: Anaplastic astrocytoma cells (H&E, original magnification x 400). C: Representative wall of the AVM showing reduplication and discontinuity of internal elastica (arrows) (Elastic van Gieson stain, original magnification x200). D: Immunohistochemical staining for VEGF showing abundant cytoplasmic staining of tumor cells (original magnification x400) (initiating and supporting their hypervascularity and increased permeability) and to AVMs (initiating and maintaining growth). Because VEGF has been implicated in the induction and/or proliferation of both AVM and malignant glioma, we elected to perform immunohistochemical stains in the case being presented. The intense staining for VEGF, which was detected in this case, provides further support for the notion that this cytokine may play an important role in triggering the de novo generation of AVM. Further neuropathologic evaluation of the tissue failed to demonstrate arterialized vessel components along with alteration in the elastica, as is commonly seen in high grade gliomas. This further supports this case as a true arterialized vascular malformation. may be a critical stimulus for the development of an AVM. REFERENCES Malcolm GP, Symon L, Tan LC, Pires M. Astrocytoma and associated arteriovenous malformation. Surg Neural 1991 ; 36: 59-62 2 Kasantikul V, Shuangshoti S, Panichabhongse V, Netsky M. Combined angioma and glioma (angioglioma). } Surg Oneal 1996; 62: 15-21 3 Nazek M, Mandybur Tl, Kashiwagi S. 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