The correlation of neoplastic vulnerability with central neuroepithelial cytogeny and glioma differentiation

Abstract

The vulnerability of neuroepithelial cells in the central nervous system (CNS) to neoplastic transformation results from the interaction of several factors: the existence of a reserve population of stem cells, the capability of differentiated cells to reenter the kinetic cycle, the number of replicating cells at risk at a particular time, the length of time during which a particular cell population remains in the cycle, the state of differentiation and the further differentiation potential of that population, and the steps of differentiation that are achieved in successive cell generations. This concept explains many aspects of CNS tumor incidence and the relationship of central neuroepithelial embryonal tumors to tumors of adult cell type. The incidence of different types of central neuroepithelial tumors can be correlated with the width of the window of neoplastic vulnerability. Examples illustrating the existence of only a narrow window include such rare tumors as medulloepitheliomas, cerebral neuroblastomas, gangliogliomas and ependymoblastomas. By contrast, cerebellar medulloblastomas, astrocytomas, mixed astrocytomas and oligodendrogliomas, and glioblastomas exemplify instances in which a relatively wider window of vulnerability exists in the light of cellular neuro-ontogeny and of the capacity of glial cells for postnatal replication. The relationship that may occasionally be established between the development of a glioma and the production of cellular gliosis such as may follow brain injury or accompany multiple sclerosis can also be viewed in the light of that concept. Increasing awareness is needed concerning the development of postradiation gliomas, in particular after the apparently successful treatment of acute lymphocytic leukemia.

Neoplasms of the central nervous system in Norway

“…The increase in glioblastoma incidence may in part be due to the progression of anaplasia in a pre-existing astrocytoma. Mixed glioma and oligodendroglioma may also, less commonly, contribute to the glioblastoma group by the same mechanism (19,20). Our findings comply with Rubinstein's concept of neoplastic vulnerability and glioma differentiation (20) and also support his experience that mixed gliomas are far more common than published figures on the relative incidence of the different glioma types seem to indicate.…”

“…The incidence of mixed gliomas is high in the present series. Generally, the range of cellular differentiating potential of tumour cells is less restricted than in non-neoplastic cells (20). Thus, the upward trend in mixed glioma incidence rate with age ( Fig.…”

Clinical Value of Pet with 18F-Fluorodeoxyglucose and L-Methyl-11C-Methionine for Diagnosis of Recurrent Brain Tumor and Radiation Injury

“…However, accumulation of IIC-Met (d) in the abnormalities on CT is similar to that of left cerebellar cortical tissue. large proportion of low grade gliomas undergo malignant transformation (23,26). FRANCAVILLA et al (6) studied 12 patients with malignant transformation of low grade glioma using FOG-PET.…”

Lucien J. Rubinstein: enduring contributions to neuro-oncology

“…Rubinstein was fascinated by these tumors and firmly insisted on maintaining a separation between the cerebellar medulloblastoma and the other embryonal neoplasms found elsewhere in the CNS, on both cytogenetic and practical grounds. 2,6,15,24,31,32,34,42,44,49,63,70,74,81,83,84,92 He supported the hypothesis that the external granular layer is the origin of the medulloblastomas. Along with Kadin and Nelson, 33 he reported the fetal granular layer adjacent to the tumor with marked neoplastic proliferation, which formed an irregular sawtooth pattern extending into the molecular layer in one patient with cerebellar medulloblastoma.…”

“…With his theory, he tried to explain radiation-induced gliomas, in particular those arising after the apparently successful treatment of acute lymphocytic leukemia. 63 Rubinstein properly documented the vascular proliferation of GBMs in vitro and in animal models. He postulated that mitogenic factors were secreted by GBM cells to promote angiogenesis.…”