On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics

Abstract

Glioblastoma multiforme (GBM) is a grade IV WHO malignant tumor with astrocytic differentiation. As one of the most common clinically diagnosed central nervous system (CNS) oncological entries, there have been a wide variety of historical reports of the description and evolution of ideas regarding these tumors. The first recorded reports of gliomas were given in British scientific reports, by Berns in 1800 and in 1804 by Abernety, with the first comprehensive histomorphological description being given in 1865 by Rudolf Virchow. In 1926 Percival Bailey and Harvey Cushing gave the base for the modern classification of gliomas. Between 1934 and 1941 the most prolific researcher in glioma research was Hans-Joachim Scherer, who postulated some of the clinico-morphological aspects of GBM. With the introduction of molecular and genetic tests the true multifomity of GBM has been established, with different genotypes bearing the same histomorphological and IHC picture, as well as some of the aspects of gliomagenesis. For a GBM to develop, a specific trigger mutation needs to occur in a GBM stem cell - primary GBM, or a slow aggregation of individual mutations, without a distinct trigger mutation - secondary GBM. Knowledge of GBM has been closely related to general medical knowledge of the CNS since these malignancies were first described more than 200 years ago. Several great leaps have been made in that time, in the footsteps of both CNS and advancements in general medical knowledge.

Identification of the role of TRPM8 in glioblastoma and its effect on proliferation, apoptosis and invasion of the U251 human glioblastoma cell line

“…Due to the limited efficacy of conventional treatments such as surgery, chemotherapy, and radiotherapy, there is an urgent need to identify novel and effective treatments. Over the past decade, numerous studies have made great progress in investigating the genetics and epigenetics of GBM (13,14). Despite advances in early diagnosis and treatment, GBM has strong invasion cababilities and is characterized by its significantly shorter patient survival among intracranial tumors (15)(16)(17)(18).…”

Glioblastoma Unique Features Drive the Ways for Innovative Therapies in the Trunk-branch Era

“…Furthermore, Scherer was the first to study several samples of the same primary bulk separately, providing evidence that the particular glioblastoma features such as microvascular hyperplasia and pseudopalisading necrosis are heterogeneously distributed within the tumor mass. 63,64 Currently, glioblastoma research studies must absolutely take into consideration both the tumor bulk and the micro-infiltrated brain parenchyma and can be carried out analyzing neoplastic and "healthy" material obtained from living patients (a), using animal models (b), studying post-mortem samples from rapid autopsies (c), comparing local and distant recurrences with the primary tumor (d).…”

“…In the literature, several studies report that both modalities enable higher resection rates and better survival outcome compared to those previously obtained with conventional microsurgery. [64][65][66][67][68] Intraoperative MRI has the advantage of revealing the modifications of the cerebral structures which continuously occur during brain surgery. However, recent work compared tumor fluorescent tissue boundaries recorded in the neuronavigation system during surgery with those of the contrast-enhancement MRI previously uploaded.…”

Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

“…According to the WHO classification of glioblastomas based on histopathological origin, it is categorised as a primary brain tumour of neuroepithelial, glial origin. 51 When glioblastoma is ranked according to its clinical and prognostic significance, it is within the highest grade IV and is highly aggressive. 52 Glioblastoma can be a result of progression from less malignant glial tumours (secondary type) or can occur de novo (primary).…”