Brainstem astroblastoma: a case report and review of the literature

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Surgical Neurology 69 (2008) 201 – 205 www.surgicalneurology-online.com

Neoplasm

Brainstem astroblastoma: a case report and review of the literature Christina Notarianni, MDa, Michelle Akin, PAa, Marjorie Fowler, MDb, Anil Nanda, MD, FACSa,4 Departments of aNeurosurgery, and bPathology, Louisiana State University Health Sciences Center-Shreveport, PO Box 33932, Shreveport, LA 71130-3932, USA Received 7 December 2005; accepted 9 December 2006

Abstract

Background: Astroblastoma is a rare glial tumor that occurs mainly in the cerebral hemispheres of young adults. Our purpose in writing this article is to report one case of astroblastoma located within the medulla and review the literature on this infrequent tumor. Methods: One case of astroblastoma was retrospectively reviewed. Presenting complaints, radiographic images, operative procedure, and histopathologic findings were recorded. Results: Contrast-enhanced MRI scan revealed a well-defined, well-circumscribed, contrastenhanced cystic lesion approximately 16 mm in diameter within the medulla oblongata. Light microscopy demonstrated a papillary neoplasm composed of mildly pleomorphic cells with indistinct cytoplasmic borders. The nuclei were generally round to oval in shape. Occasional rosettes of tumor cells were seen around blood vessels. Mitoses were not seen within the submitted specimen. One small area of necrosis was present. The tumor exhibited thickened but not hyalinized blood vessel walls. The tumor cells exhibited strong staining for EMA and vimentin throughout the tissue section. Neurofilament, CAM 5.2, and CK immunostains were negative, except for rare positive staining of CK between cells and within rare tumor cells. Ki-67 was positive in small numbers of tumor nuclei, with an overall reactivity of 7%. By electron microscopy, the tumor nuclei had irregularly round to oval nuclei with moderate clumping of the chromatin, especially at the nuclear margins. Conclusions: The combination of the radiologic and histopathologic characteristics of this tumor is necessary for making the diagnosis of astroblastoma. This article serves to summarize these characteristics as well as to report of an unusual location for this mainly hemispheric tumor. D 2008 Elsevier Inc. All rights reserved.

Keywords:

Astroblastoma; Brainstem; Tumor

1. Introduction Astroblastoma is a rare glial tumor that occurs mainly in the cerebral hemispheres of young adults [12]. Classified in 1924 by Bailey and Cushing, the first reported series followed in 1930 by Bailey and Bucy, who regarded the tumor as a distinct neoplasm with an intermediate prognosis

between that of astrocytoma and glioblastoma [12]. The radiologic and histopathologic features of this tumor help differentiate it from the more common ependymoma and astrocytoma. Here we review the recent literature on this infrequent tumor, focusing on the radiologic and histopathologic findings, and present an illustrative case. 2. Literature review

Abbreviations: CAM; CK, Cytokeratin; CSF, Cerebrospinal fluid; CT, Computed tomography; EMA, Epithelial membrane antigen; FDG, F-18 fluorodeoxyglucose; FLAIR, Fluid-attenuated inversion-recovery imaging; GBM, Glioblastoma multiforme; GFAP, Glial fibrillary acid protein; MRI, Magnetic resonance imaging; NF, Neurofilament; NSE, Neuron-specific enolase; PET, Positron emission tomography. 4 Corresponding author. Tel.: +1 318 675 7352; fax: +1 318 675 7111. E-mail addresses: [email protected], [email protected] (A. Nanda). 0090-3019/$ – see front matter D 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2006.12.045

A literature search was performed using the National Library of Medicine PubMed search engine. The keywords astroblastoma and brainstem were used to identify articles. More than 1000 articles were returned; however, many of these did not pertain directly to astroblastoma, but rather, astrocytic tumors, and thus were not included in this literature review. The relevant literature on this subject

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consists of mainly small case reports, the largest being that of 23 tumors reported by Bonnin and Rubenstein in 1989. The articles that were included in this review specifically addressed at least one case presentation of a histopathologically confirmed astroblastoma located within the hemispheres or within the brainstem. Specifically, 19 relevant articles were analyzed regarding presentation, imaging, and histopathologic findings for this discussion. This review is directed toward the imaging and histopathologic characteristics that help distinguish this tumor from other tumors, in particular, astrocytoma and ependymoma. 3. Case report This 20-year-old white woman presented with a 6-month history of occipital headaches and a 2-month history of left lower extremity numbness, diplopia, blurred vision, and

ataxia. Neurologic examination revealed intact extraocular movements with left beating nystagmus. Paresthesias in the left lower extremity were also noted. A noncontrasted CT scan did not show any abnormalities. However, a contrastenhancing MRI scan revealed a well-defined, wellcircumscribed, contrast-enhancing cystic lesion approximately 16 mm in diameter within the medulla oblongata (Fig. 1). The lesion had a nodule along the left medial border that enhanced more intensely than the remainder of the lesion. A PET scan of the brain revealed that the medullary lesion did not have avidity for FDG. Grossly, the tumor was totally resected through a far lateral transcondylar approach. Postoperatively, the patient experienced some difficulty swallowing and right-sided weakness. These problems resolved completely by her 3-month followup visit. Repeated MRI scans show no residual tumor. The patient did not receive any radiation therapy.

Fig. 1. Axial, coronal, and sagittal T1-weighted MRI images, post contrast, demonstrating an enhancing lesion located within the medulla oblongata.

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Fig. 2. Hematoxylin and eosin stain at 20 and 40 magnification displaying pseudorosettes of tumor cells around vessels and thickened vessel walls.

The result of the pathologic examination of the tumor was consistent with astroblastoma. Light microscopy demonstrated a papillary neoplasm composed of mildly pleomorphic cells with indistinct cytoplasmic borders. The nuclei were generally round to oval in shape. Occasional rosettes of tumor cells were seen around blood vessels (Fig. 2). Overall, the tumor was very vascular with thickened but not hyalinized blood vessel walls. The tumor cells exhibited strong staining for EMA and vimentin throughout the tissue section. Glial fibrillary acid protein was also focally positive in many of the epithelioid cells mostly near the blood vessels. S-100 immunostain also reacted positively throughout the tumor cells. Neurofilament, CAM 5.2, and CK immunostains were negative. Quantitative computer-assisted analysis of Ki-67 immunoreactivity within the tumor showed a Ki-67 labeling index of approximately (or up to) 7%. 4. Discussion Astroblastoma is a rare glial tumor that usually occurs within the cerebral hemispheres. The first reported series on

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this neoplasm was by Bailey and Bucy in 1930 who considered the prognosis for the tumor to be intermediate between that of astrocytoma and glioblastoma [12]. Recent literature supports the initial impression by Bailey and Bucy that the tumor is a separate entity, although controversy still exists as to the exact cell of origin of the tumor [2,5,6,8,20]. The World Health Organization Classification of Tumors in 2000 supported this position by classifying the astroblastoma as a separate entity. However, the tumor was placed in the category of neuroepithelial tumors of unknown origin, rather than within the category of astrocytic neoplasms, an acknowledgment of the still unknown cell of origin [9]. Most cases of astroblastoma have been described in young adults, although reports of congenital astroblastoma have been documented [11,12]. Neuroradiologically, the astroblastoma is portrayed as a well-circumscribed, superficial lesion most commonly within the cerebral hemispheres [1,2,12,13,15]. It often has solid and cystic components, both of which will contrast enhance [1,12,16]. The distinction between well-differentiated and malignant astroblastomas cannot be made by radiologic examinations [13]. Both appear as discrete lesions, well demarcated from the surrounding brain [2]. By CT scan, most hemispheric lesions will be identified as large masses, usually superficially located, which heterogeneously contrast enhance [5,7,12,13,16,17,20,21]. The MRI findings of the solid component of the tumor have been described as hypointense on TI-weighted images [13,15]. The T2-weighted images of the solid area of the lesion are isointense [13]. Contrast enhancement has been characterized as being heterogeneous throughout the lesion, with rim enhancement of the cystic portions of the tumor [2,13,15]. Sener also noted that the signal pattern of the cyst structures within the tumor was different from CSF, giving a high signal on FLAIR imaging. This finding suggested the presence of viscous material. Little peritumoral hyperintensity on T2-weighted scans was also a feature noted in the literature [13,15]. This characteristic helps distinguish the lesion from other more common tumors such as ependymoma, anaplastic astrocytoma, and GBM, all of which have moderate to significant peritumoral hyperintensity on T2-weighted scans [13]. Histopathologically, astroblastomas exhibit characteristic epithelioid cells with broad tapering processes in a perivascular pattern, forming pseudorosettes of tumor cells around vessels, similar to ependymomas [1,14,18 -20]. These pseudorosettes, however, do not contain fibrillary material within their cytoplasm. It is this lack of fibrillarity that helps distinguish these pseudorosettes from those found in ependymomas [2,12] Moreover, the cellular processes that are found in astroblastomas are shorter and broader than those that are seen in ependymoma, helping distinguish these 2 lesions histopathologically [12,17]. Furthermore, between the pseudorosettes are rarified spaces, in contrast to the compact intravascular architecture of the ependymoma [12,20].

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Another attribute found in astroblastomas is perivascular hyaline formation [2,8]. The amount of hyaline varies from case to case; but in the most severe forms, expansive, acellular hyalinized zones will be seen without any residual tumor architecture [2]. Most cases, though, consist of highly packed pseudorosettes of tumor cells [1,2]. Papillary appearances can also be formed by the tumor as a result of hyalinized pseudorosettes in less cellular regions of tumor [1-4,6,10]. These distinctive histopathologic features alone are nonspecific and can be found in a variety of astrocytic tumors, such as GBM, ependymoma, and primitive neuroepithelial tumors [2]. In the past, finding this histology focally within other tumors delayed the classification of astroblastoma as a distinct entity. Now, current literature supports the position that if these histopathologic features are found throughout a specimen, the lesion may be characterized as an astroblastoma. However, focal findings in another type of neoplasm such as an astrocytoma or ependymoma are not enough to classify it as an astroblastoma [2,4,12]. As evidenced by radiologic imaging, most astroblastomas are well circumscribed with pushing borders. This characteristic is also seen histologically, as the tumor rarely infiltrates into the surrounding tissue [4,10]. Highergrade lesions will occasionally have clusters of tumor cells extending marginally into surrounding brain; however, there are no reports of diffuse infiltration of the surrounding tissue [2]. This is an important characteristic to help distinguish the lesion from that of a fibrillary astrocytoma, which commonly infiltrates the nearby brain tissue [2]. Immunohistochemical features of astroblastoma have some variability throughout the literature, which adds to the controversy of the cell of origin of the tumor. Positive staining for GFAP, an intermediate filament of glial origin, is demonstrated in astroblastomas, lending support to the theory that the tumor cell is derived from an astrocyte cell line [5,6,12,14,20]. Astroblasts also consistently stain positive with vimentin, a more primitive intermediate filament of neuroepithelial origin, suggesting derivation from a more primitive astroblast [4,5,16]. However, some authors have noticed scarce positivity of GFAP in their studies despite the large presence of intermediate filaments by electron microscopy [4,6,20]. These immunohistochemical findings have suggested that there may be stages of differentiation within astroblastic tumor cells in the type of filament they produce [4,7]. Other immunostains, such as NSE, EMA, CK, and CAM 5.2, tested on this tumor have had highly variable results in the current literature and have not shown any overall pattern to help characterize astroblastomas histologically [4,5,7,10,12,17]. Certainly, controversy still exists in the literature of the cell of origin of astroblastoma. However, the recent literature on this tumor has set forth several characteristics

of this lesion that serve to differentiate this tumor from, most commonly, astrocytoma and ependymoma. The combination of the radiologic and the histopathologic characteristics of this tumor is necessary for making the diagnosis of astroblastoma. This article serves to summarize these characteristics as well as to report of an unusual location for this mainly hemispheric tumor.

Acknowledgment The authors thank Ms Sapna McManus for her editorial assistance.

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