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Table of Contents    
Year : 2011  |  Volume : 59  |  Issue : 6  |  Page : 918-920

Glioblastoma multiforme with epithelial differentiation

1 Department of Pathology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala, India
2 Department of Neurosurgery, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala, India
3 Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala, India

Date of Submission17-Jun-2011
Date of Decision21-Jul-2011
Date of Acceptance02-Sep-2011
Date of Web Publication2-Jan-2012

Correspondence Address:
V V Radhakrishnan
Department of Pathology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.91386

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How to cite this article:
Neelima R, Gopalakrishnan C V, Thomas B, Radhakrishnan V V. Glioblastoma multiforme with epithelial differentiation. Neurol India 2011;59:918-20

How to cite this URL:
Neelima R, Gopalakrishnan C V, Thomas B, Radhakrishnan V V. Glioblastoma multiforme with epithelial differentiation. Neurol India [serial online] 2011 [cited 2021 Jun 20];59:918-20. Available from:


Epithelial component in glioblastoma multiforme (GBM) is an uncommon histopathological feature. This report describes salient light microscopic as well as immunohistochemical features in a case of GBM with epithelial component.

A 49-year-old female presented with headache of one-month duration. On examination ocular fundi revealed papilloedema. Magnetic resonance imaging (MRI) brain showed multiple conglomerate well-defined peripherally enhancing cystic lesions in the right temporal pole extending medially. Another larger separate cyst with an enhancing solid component was present in the right posterior temporal peri-sylvian region [Figure 1]. Both the lesions demonstrated high perfusion on MRI. Intraoperatively, multiple conglomerate cystic lesions were seen; right temporal lobectomy and excision of posterior temporal lesion was performed. Hematoxylin and eosin-stained sections of the lesion from the temporal pole showed features suggestive of a GBM [Figure 2]a-c. Histopathology of the cyst wall from the posterior temporal lesion showed features of a glioma admixed with small cuboidal cells arranged in tubular/adenoid and lobular patterns [Figure 2]d-f. These cells mimicked those of a metastatic carcinoma. The neoplastic glial cells were strongly positive for gliofibrillary acidic protein (GFAP) [Figure 3]a whereas the epithelial cells showed only focal positivity (GFAP; 1:100) [Figure 3]b. The epithelial cells demonstrated strong cytoplasmic positivity for epithelial membrane antigen (EMA; 1:100) [Figure 3]c, and focal positivity for high molecular weight cytokeratin (HMWCK; 1:100 [Figure 3]d).

These morphological features along with immuno-histochemical profile suggested a diagnosis of GBM with epithelial differentiation.
Figure 1: Axial T1-weighted (a) and T2-weighted (b) MRI brain showing heterogeneous signal intensity mass lesions in the temporal pole with significant perilesional edema and mass effect. Post-contrast axial T1-weighted image (c) demonstrates the enhancing cyst walls and the conglomerate ring-like lesions situated anteriorly in the temporal pole. Contrast-enhanced sagittal T1-weighted fat saturated image (d) is showing heterogeneously enhancing necrotic lesion involving the right temporal pole. Note another large cystic lesion situated in the posterior temporal lobe just inferior to the sylvian sulcus

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Figure 2: (a) Photomicrograph of lesion from temporal pole showing classical features of a glioblastoma with foci of endothelial proliferation (b) and extensive necrosis (c). The lesion from the posterior temporal peri-sylvian region showing pleomorphic fibrillary and gemistocytic astrocytes (d, e) admixed with epithelial cells in lobular (arrows) and adenoid patterns (f). (Hematoxylin and Eosin; a, b, c, e, f × 200: d × 400)

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Figure 3: (a) The neoplastic glial cells with strong positivity for GFAP and the majority of the epithelial cells were negative except for a small focus (b). The epithelial cells were diffusely and strongly immunoreactive for epithelial membrane antigen (c) and focally positive for high molecular weight cytokeratin (d). (Immunostaining Avidin-Biotin Complex a, b, c, d, × 400)

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Varying terminology has been used to describe epithelial differentiation in GBM. Kepes et al., [1] observed focal arrangement of neoplastic cells in cribriform, trabecular and pseudoacinar pattern which they referred to as adenoid formation in gliosarcoma. Rodriguez et al., [2] suggested two patterns of differentiation: those with pseudoepithelial components (adenoid or epithelioid) and with true epithelial (squamous or glandular structures) components. The histopathologic features of epithelioid GBM can be erroneously diagnosed as metastatic carcinoma. [1],[3] The cells in the epithelial component of GBM, like metastatic carcinoma, often yield positive immunostaining for cytokeratin and this can pose diagnostic difficulties. However, these epithelial cells will also show focal positivity for GFAP and this feature helps to distinguish it from metastatic carcinoma. [2],[3]

A number of studies have suggested the probable mechanisms of epithelial differentiation in GBM. Bigner et al., [4] suggested that these epithelial arrangements might represent the phenotype of primitive, multipotential neuroepithelial cells. Kepes et al., [1] pointed out that a primitive astrocyte might exhibit a cuboidal appearance and this could be due to mechanical compression. Mork et al., [5] commented that these epithelial cells are unusual expressions of anaplasia. Shintaku et al., [6] considered that the epithelial structures in GBM were due to the histological response of host cells to the tumor. Ultrastructural studies showed these cell arrangements represented primitive cells with immature junctions and organelles, and with no evident epithelial differentiation. [1],[6] This was later supported by similar clonal origin in both glial and epithelial components in studies done by Rodriguez et al. [2] Based on these available literature surveys it is probable that the epithelial structures are derived from neuroepithelial cells. Rodriguez et al., [2] found no significant prognostic difference in GBM with and without epithelial differentiation. Long-term case-control studies are essential to establish the significance of the epithelial component of GBM in tumor behavior.

The neuropathologist and oncologist should be familiar with the epithelial variant of GBM, albeit rare. Immunohistochemistry in conjunction with preoperative imaging would help in clinching the diagnosis. Nevertheless, patients with multifocal lesions and a pathological diagnosis of epithelioid GBM warrant a systemic survey for primary malignancy.

  References Top

1.Kepes JJ, Fulling KH, Garcia JH. The clinical significance of adenoid formations of neoplastic astrocytes, imitating metastatic carcinoma, in gliosarcomas. A review of five cases. Clin Neuropathol 1982;1:139-50.  Back to cited text no. 1
2.Rodriguez FJ, Scheithauer BW, Giannini C, Byrant SC, Jenkins RB. Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma: A comparative morphologic and molecular genetic study. Cancer 2008;113:2779-89.  Back to cited text no. 2
3.Gasco J, Franklin B, Fuller GN, Salinas P, Prabhu S. Multifocal epithelioid Glioblastoma mimicking cerebral metastasis: Case report. Neurochirugia (Astur) 2009;20:550-4.  Back to cited text no. 3
4.Bigner DD, McLendon RE, Bruner JM. Russel and Rubinstein's Pathology of tumors of the nervous system, 6 th ed. Arnold: London; 1998. p. 437-9.  Back to cited text no. 4
5.Mork SJ, Rubinstein LJ, Kepes JJ. Patterns of epithelial metaplasia in malignant gliomas. I. Papillary formations mimicking medulloepithelioma. J Neuropathol Exp Neurol 1988;47:93-100.  Back to cited text no. 5
6.Shintaku M, Nakatsu S, Okamoto S. Adenoid glioblastoma. No Shinkei Geka 2000;28:359-65.  Back to cited text no. 6


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