Hans Joachim Scherer and His Impact on the Diagnostic, Clinical, and Modern Research Aspects of Glial Tumors

Abstract

The historical descriptions of glial tumors are often poorly understood and interpreted. The gross and histological depictions of glial tumors are often credited to Virchow, and while the first true histological description is truly his, gross descriptions can be traced back to the beginning of the 1800s, with their classification and histogenesis attributed to Percival Bailey and Harvey Cushing. Without any question, the most prominent and under-credited researcher in the field of glioma pathobiology was the German neuropathologist Hans Joachim Scherer. Despite the limited armamentarium available to him, his systematic approach led to conclusions, some of which have now been molecularly explained today while some are still being widely researched. Scherer defined pseudopalisadic necrosis as a pathognomonic feature of glioblastoma multiforme (GBM), as well as secondary features due to tumor growth, known collectively as secondary Scherer figures, for example, neuronal and vascular satellitosis, tract and subpial aggregation. All these features are key points in the modern histological diagnosis of glial tumors. Other contributions by Scherer include the definition of glomeruloid vascular proliferation and his conclusion that they are caused by vascular factors released by the tumor, decades before vascular endothelial growth factor and its receptors were discovered and their role in glioma evolution was established. Furthermore, he concluded that GBMs can arise de novo (primary) or from a preceding lower-grade glioma (secondary). All his contributions find their place in all modern aspects of glioma research, with some giving a simple explanation of the phenomena observed in glial tumors.

Historical origin and meaning of the term „glial tumor“

“…The German neuropathologist Hans Joachim Scherer made huge contributions to the diagnosis and classification of glial tumors, although for many years he remained unappreciated for political reasons. 10 His work reached conclusions categorically proven and explained only after the introduction of molecular analysis and genetic research. For the first time, he introduced the term arising de novo "primary glioblastoma" and "secondary glioblastoma" -arising on the basis of a preceding low-grade neoplasia of the astrocytic line, paying attention not only to their origin, but also to the prognosis and differences in the course of the disease.…”

Cerebral Glioblastoma: A Review on Genetic Alterations, Signaling Pathways, and Clinical Managements

“…The existence of PTEN is necessary due to its capability to inhibit the PI3K signaling (3,10,11,16). PTEN is a multifunctional tumor suppressor and a genome stabilizer that has important effects on many biological processes, including cell growth, cell proliferation, cell survival, cell invasion, and cell migration (3,8). Loss of PTEN results in the accumulation of PKB due to the loss of PI3K blockage (8,16).…”

“…PTEN is a multifunctional tumor suppressor and a genome stabilizer that has important effects on many biological processes, including cell growth, cell proliferation, cell survival, cell invasion, and cell migration (3,8). Loss of PTEN results in the accumulation of PKB due to the loss of PI3K blockage (8,16). Although PTEN mutation almost exclusively occurs in primary glioblastoma, EGFR amplification accompanied by EGFRvIII, the most common deletion mutation in the extracellular domain of EGFR in human cancer, stays on the top of the list of primary glioblastoma genetic alterations (3,14).…”

“…There is also a molecular classification for glioblastoma that comprises of four subtypes, based on the gene alteration (2), as follows classic, mesenchymal, proneural, and neural glioblastomas (Table 1) (2). Because of the cellular complexity of glioblastoma and the atypical-multiform appearance of its cells (that vary in size and shape), the term 'spongioblastoma multiform' was introduced by Bailey and Cushing in 1926 (2,(4)(5)(6)(7)(8). Glioblastoma was previously known as 'spongioblastoma multiform'.…”

“…Despite different methods available for diagnosis, treatment, and management of patients with glioblastoma, prognostic factors such as age, gender, the extent of tumor resection, and neurological status play an important role in the overall outcome of a patient (1,3,9). While various factors can be used to classify glioblastoma, generally, it is characterized into primary and secondary glioblastomas (Table 2) (3,9,10), which was first presented by Hans Joachim Scherer (1906 -1945), the German neuropathologist (3,8). Primary glioblastoma, also known as wild-type IDH (wild-type isocitrate dehydrogenase) glioblastoma, is the most common type of glioblastomas, accounting for more than 90 percent of cases (incidence rate: 2.578 per 100000 people per year according to World Standard Population) and the time between its emergence and development is so short that no specific clinical or histological evidence of a less malignant precursor can be observed, which is the main reason that it is named as 'de Novo' glioblastoma (3,5,10).…”