The Story of Glioblastoma: History and Modern Correlates

History of glioblastoma: from trephination to World Health Organization classification

Although evidence of trephination or trepanation has been found from ancient cultures dating back to the late Paleolithic period from around the world, the first medical description of the procedure was documented by Hippocrates. Practitioners performed trephination for traumatic injuries (to elevate depressed skull fractures) and for a variety of other reasons, including to alleviate seizures, headaches, superficial growths, and psychiatric maladies ( Fig. 1.1 ). The ancient physician and surgeon, Abu al-Qasim Al-Zahrawi (Latinized to Albucasis) of Andalusia, developed and described numerous surgical instruments and procedures in the volumes of Kitab al-Tasrif (The Method of Medicine), including operations to treat neurosurgical disorders. These disorders included tumors of the central nervous system.

The acceptance and formalization of the scientific method, advancements in clinical and laboratory medicine, and the development of equipment like the light microscope brought forth new knowledge and opportunities to study human disorders. Between 1856 and 1865, Rudolph Ludwig Carl Virchow first described neuroglia, defined the gliomas and separated them into what are now considered low-grade and high-grade disorders, and developed the foundation for pathologic study. At the time, tumors found in the brain at autopsy were named according to the presumed (normal) cellular counterpart. Given the available staining and visualization techniques, many of the cell types that are now considered glial cells were not clearly defined; they were thought of as elements of connective tissue without a cellular origin. Based on Camilo Golgi’s work in identifying foot processes along neurons (1873), and Michael von Lenhossék’s description of the astrocyte (1891), the idea that glial cells provided support for neurons was propagated. Santiago Ramón y Cajal and Pío del Río-Hortega contributed much to the understanding of glial cells and the cellular architecture of the brain using gold-based (labeling glial fibrillary acidic protein) and platinum-based (labeling oligodendrocytes) agents.

In 1926, Percival Bailey and Harvey Cushing, both American Midwesterners by birth and upbringing, collaborated to publish A Classification of the Tumors of the Glioma Group on a Histogenetic Basis with a Correlated Study of Prognosis . Bailey used histologic staining techniques to study 254 gliomas from Cushing’s series. These and an additional 160 gliomas were used in classifying 13 groups according to the cellular configuration. The classification scheme was later condensed. In addition, tumors were grouped according to patient survival. Before this work, central nervous system tumors were generally considered gliomas; prognosis was not clearly linked to histopathologic diagnosis. Because of the important and practical implications of this work, it was received with great interest worldwide ( Figs. 1.2–1.4 ).

Cushing and Bailey identified spongioblastoma multiforme as a distinct tumor with a specific cell of origin based on its histologic appearance, which appeared different from the other gliomas (see Fig. 1.2 ). Despite heterogeneity (prompting the term multiforme) when visualized under the microscope, patients with these tumors uniformly experienced rapid declines in their clinical trajectories. By the 1940s, spongioblastoma multiforme became better known as glioblastoma multiforme.

The German neuropathologist Hans Joachim Scherer first hypothesized the concept of primary versus secondary glioblastoma in 1938 and published a series of articles substantiating this into the 1940s. His ideas were ahead of his time in both a theoretic and scientific sense. He noted that patients with secondary glioblastoma had long clinical courses compared with those with primary glioblastoma, emphasizing that they could be distinguished from biological and clinical perspectives. Although this was noted by both Scherer and Cushing, both were in disagreement over systems of classification. Penfield, Kernohan, Sayre, Schaffer, Bergstrand, Purdy, and Olivecrona proposed differing systems of classification based on novel clinical and histopathologic findings; these systems were introduced with considerable bias.

A consensus system for classification was needed. From 1956 to 1979, the World Health Organization (WHO) recruited 23 centers worldwide consisting of approximately 300 pathologists to provide microscopic samples of brain tumors for classification. In 1979, the first edition of the WHO Classification of Tumors of the Central Nervous System was published. Subsequent editions were published in 1982, 2000, and 2007. At the time of this writing, a fifth edition is due for release (See Chapter 4 for details).