Glioblastoma Multiforme

Glioblastoma (also known as glioblastoma multiforme, or GBM), is most frequently diagnosed among the elderly, with a median age of diagnosis being 64 years and a significant predilection toward male gender [1] [2]. However, pediatric cases have also been documented, in whom an even stronger male predilection exists [1]. Although glioblastomas are not that common (incidence rate is about 2-5 per 100,000 individuals), they carry a very poor prognosis [1] [2]. Overall survival rarely exceeds 12-14 months from the time of diagnosis, which is why, according to the World Health Organization criteria (WHO), it is classified as a stage IV astrocytoma [3] [4] [5]. One of the reasons why such a poor outcome is expected is that GBM is often missed in its initial stages due to a nonspecific symptomatology and physicians often turn their attention to infections, vascular processes or immunological diseases prior to suspecting neoplastic disorders [1]. The clinical presentation initially includes headaches (due to increased intracranial pressure caused by the tumor), vomiting, nausea, frequent syncope and seizures, which may be the only sign in patients without a previous history of epilepsy [1] [6]. In time, cognitive dysfunction can appear, as well as gait disturbances, cranial nerve palsies, urinary incontinence, hemiparesis, aphasia, and disorientation, while vertigo is described in a minority of cases [1] [2] [6]. Moreover, various psychiatric manifestations have been described in patients with glioblastomas, such as personality disorders, loss of emotional control and anger, mood disorders (depression, mania) and marked anxiety, whereas hallucinations and psychosis, although rare, have also been observed [7].

A complete physical workup is essential in order to place glioblastoma into the differential diagnosis of nonspecific central nervous system (CNS) symptoms and associated features. Firstly, a detailed patient history can reveal a history of epilepsy, the appropriate age for the development of glioblastoma (elderly patients) and a somewhat sudden onset of symptoms. Secondly, a thorough physical examination confirms the presence of neurological deficits and roughly determines the area of the brain that is affected by the underlying disorder. To solidify the diagnosis, imaging studies are the modality of choice, ranging from computed tomography (CT) and magnetic resonance imaging (MRI) to more advanced methods, such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) [2]. MRI, and even CT, however, are often sufficient to confirm the tumor, and the mean diameter at the time of diagnosis is about 4 cm [1]. An enhancing heterogeneous mass with areas of central necrosis and surrounding edema is the typical presentation [2]. Despite evident clinical and imaging criteria, a definite diagnosis can only be made after obtaining a valid sample for biopsy and a histopathological examination with immunohistochemistry [1] [2]. Postoperative sampling is mandatory, while in cases when the tumor is not resectable, a fine needle aspiration or stereotactic biopsy can be performed [1] [2]. The decreased presence of glial fibrillary acidic protein (GFAP) in glioma cells, as well as S100 positivity on immunohistochemistry, is important in the diagnosis of glioblastoma [1].

1. Urbańska K, Sokołowska J, Szmidt M, Sysa P. Glioblastoma multiforme – an overview. Contemporary Oncology. Contemp Oncol (Pozn). 2014;18(5):307-312.
2. Mesti T, Ocvirk J. Malignant gliomas: old and new systemic treatment approaches. Radiol Oncol. 2016;50(2):129-138.
3. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica. 2007;114(2):97-109.
4. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
5. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
6. Sanli AM, Turkoglu E, Dolgun H, Sekerci Z. Unusual manifestations of primary Glioblastoma Multiforme: A report of three cases. Surg Neurol Int. 2010;1:87.
7. Boele FW, Rooney AG, Grant R, Klein M. Psychiatric symptoms in glioma patients: from diagnosis to management. Neuropsychiatric Disease and Treatment. 2015;11:1413-1420.