tumor and is composed of infiltrative and diffuse tumor cells that reside amongst histo-logically normal brain where the BBB remains intact.
In 1938, Scherer carefully documented the diffusely invasive growth pattern of HGGs and correctly predicted that this biological property of HGGs would limit the ability to surgically cure these tumors . Further confirmation of these studies came with the advent of CT and MR imaging. Histological analysis of stereotac-tic biopsies taken from radiographically defined regions of HGGs consistently demonstrates the presence of tumor cells beyond areas of contrast enhancement, with infiltration of tumor tissue and/or isolated tumor cells throughout areas of CT hypodensity and prolonged T2 signal on MR images. In a study by Kelly et al., only 18 out of 186 biopsy samples from regions of prolonged T2 signal had no evidence of isolated tumor cells or tissue . Furthermore, isolated tumor cells can be detected histologically or cultured from HGG biopsy samples that are obtained from regions of radiographically normal brain .
Aside from limiting the ability to effectively resect HGGs, this invasive and diffuse growth pattern likely underlies the demonstration of functional cortex in areas of brain that are infiltrated or grossly involved by tumor . In addition, the presence of an intact BBB in this region limits the ability to deliver many therapeutic agents that rely on its breakdown to achieve cytotoxic doses. While neurosurgical management is generally focused on maximal resection of the central region of necrosis and solid or bulk tumor that contributes primarily to mass effect, emerging treatment modalities that address the invasive tumor component may require neurosurgical expertise as well (see below).
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