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The great imitator - EMA positive glioblastoma multiforme

George St. Stoyanov, Deyan Dzhenkov, Peter Ghenev


INTRODUCTION: Glioblastoma multiforme (GBM) has always been a diagnostic challenge for pathologists. As a rare oncological entry with astrocytic differentiation, it can manifest itself in a variety of histomorphological forms, mimic other tumors and it often has varying immunohistochemical (IHC) profiles, further challenging the process of its verification.

MATERIALS AND METHODS: Four pathologically verified cases of GBM, registered at the St. Marina University Hospital, Varna, Bulgaria were retrieved from the central pathological archive. The cases were tested and reviewed based on their hematoxylin and eosin (H&E) profiles and IHC reactions with GFAP used as a glial differentiation marker, Vimentin - as a positive IHC control and EMA, an epithelial marker, non-reactive in healthy brain tissue.

RESULTS: As expected all GBM cases had the histomorphological hallmarks of the tumor on the H&E stain. They were diagnostically positive for GFAP and had a strong positive IHC reaction with Vimentin. Three out of the four cases also revealed a varying in intensity reaction with EMA, with one case having a weak reaction in individual cells that could not be considered diagnostic and the other two cases having a diffuse positive reaction in most of the tumor cells.

CONCLUSION: In the age of immunohistochemistry, GBM continues to expand the set of IHC markers that react with it, although several of them such as Cytokeratin AE1/AE3 and EMA, as demonstrated in this study, should be non-reacting as they react with proteins normally present only in epithelial cells and absent in healthy brain tissue. This can often be misleading and, in certain cases, lead to histopathological misdiagnosis.


GBM, IHC, EMA, CNS tumor, pathology, antibody mimicry

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Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114(2):97-109.

Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol 2012;14 Suppl 5:1-49.

Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz- Sloan JS. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol 2013;15 Suppl 2:1-56.

Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz- Sloan J. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol 2014;16 Suppl 4:1-63.

Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz- Sloan JS. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol 2015;17 Suppl 4:1-62.

Fogelholm R, Uutela T, Murros K. Epidemiology of central nervous system neoplasms. A regional survey in Central Finland. Acta Neurol Scand 1984;69(3):129-36.

Guomundsson KR. A survey of tumors of the central nervous system in Iceland during the 10-year period 1954-1963. Acta Neurol Scand 1970;46(4):538-52.

Walker AE, Robins M, Weinfeld FD. Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology 1985;35(2):219-26.

Kepes JJ. Astrocytomas: old and newly recognized variants, their spectrum of morphology and antigen expression. Can J Neurol Sci 1987;14(2):109-21.

Kriho VK, Yang HY, Moskal JR, Skalli O. Keratin expression in astrocytomas: an immunofluorescent and biochemical reassessment. Virchows Arch 1997;431(2):139-47.

Goswami C, Chatterjee U, Sen S, Chatterjee S, Sarkar S. Expression of cytokeratins in gliomas. Indian J Pathol Microbiol 2007;50(3):478-81.

Cosgrove MM, Rich KA, Kunin SA, Sherrod AE, Martin SE. Keratin intermediate filament expression in astrocytic neoplasms: analysis by immunocytochemistry, western blot, and northern hybridization. Mod Pathol 1993;6(3):342-7.

GFAP - DAKO antibody description. [Internet] Dako c2016. Available from:

Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem Res 2000;25(9-10):1439-51.

Vimentin - DAKO antibody description. [Internet] Dako c2016. Available from:

EMA - DAKO antibody description. [Internet] Dako c2016. Available from:

Cosgrove M, Fitzgibbons PL, Sherrod A, Chandrasoma PT, Martin SE. Intermediate filament expression in astrocytic neoplasms. Am J Surg Pathol 1989;13(2):141-5.

Hasselblatt M, Paulus W. Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. Acta Neuropathol 2003;106(4):385-8.

He MX, Wang JJ. Rhabdoid glioblastoma: case report and literature review. Neuropathology 2011;31(4):421-6.

Preusser M, Hoischen A, Novak K, Czech T, Prayer D, Hainfellner JA, Baumgartner C, Woermann FG, Tuxhorn IE, Pannek HW, Bergmann M, Radlwimmer B, Villagrán R, Weber RG, Hans VH. Angiocentric glioma: report of clinico-pathologic and genetic findings in 8 cases. Am J Surg Pathol 2007;31(11):1709-18.

DeAngelis LM, Mellinghoff IK. Virchow 2011 or how to ID(H) human glioblastoma. J Clin Oncol 2011;29(34):4473-4.

Crespo I, Vital AL, Gonzalez-Tablas M, Patino Mdel C, Otero A, Lopes MC, de Oliveira C, Domingues P, Orfao A, Tabernero MD. Molecular and Genomic Alterations in Glioblastoma Multiforme. Am J Pathol 2015;185(7):1820-33.

Masui K, Mischel PS, Reifenberger G. Molecular classification of gliomas. Handb Clin Neurol 2016;134:97-120.

Wirsching HG, Galanis E, Weller M. Glioblastoma. Handb Clin Neurol 2016;134:381-97.

Masui K, Komori T. Molecular Genetics as Best Evidence in Glioma Diagnostics. Brain Nerve 2016;68(3):253-61.

Vigneswaran K, Neill S, Hadjipanayis CG. Beyond the World Health Organization grading of infiltrating gliomas: advances in the molecular genetics of glioma classification. Ann Transl Med 2015;3(7):95.

Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O`Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98-110.

Neumann JE, Dorostkar MM, Korshunov A, Mawrin C, Koch A, Giese A, Sch├╝ller U. Distinct Histomorphology in Molecular Subgroups of Glioblastomas in Young Patients. J Neuropathol Exp Neurol 2016 [Epub ahead of print].

Antoch G, Vogt FM, Freudenberg LS, Nazaradeh F, Goehde SC, Barkhausen J, Dahmen G, Bockisch A, Debatin JF, Ruehm SG. Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology. JAMA 2003;290(24):3199-206.



About The Authors

George St. Stoyanov
Medical University of Varna

Department of General and Clinical Pathology, Forensic Medicine and Deontology

Deyan Dzhenkov
Medical University of Varna

Department of General and Clinical Pathology, Forensic Medicine and Deontology

Peter Ghenev
Medical University of Varna

Department of General and Clinical Pathology, Forensic Medicine and Deontology

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