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Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype

Departments of Neurological Surgery (D.A.L., S.C., E.K., M.S.B.), Radiology (S.C., M.C.M., M.-H.C.), and Neuropathology (S.V.), University of California, San Francisco, San Francisco, CA 94143, USA

Address correspondence to Daniel A. Lim or Mitchel S. Berger, Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus St., M779, Box 0112, San Francisco, CA 94143, USA (limd{at}neurosurg.ucsf.edu or bergerm{at}neurosurg.ucsf.edu).

Neural stem cells with astrocyte-like characteristics exist in the human brain subventricular zone (SVZ), and these cells may give rise to glioblastoma multiforme (GBM). We therefore analyzed MRI features of GBMs in specific relation to the SVZ. We reviewed the preoperative and serial postoperative MR images of 53 patients with newly diagnosed GBM. The spatial relationship of the contrast-enhancing lesion (CEL) with the SVZ and cortex was determined preoperatively. Classification was as follows: group I, CEL contacting SVZ and infiltrating cortex; group II, CEL contacting SVZ but not involving cortex; group III, CEL not contacting SVZ but involving cortex; and group IV, CEL neither contacting SVZ nor infiltrating cortex. Patients with group I GBMs (n = 16) were most likely to have multifocal disease at diagnosis (9 patients, 56%, p = 0.001). In contrast, group IV GBMs (n = 14) were never multifocal. Group II (n = 14) and group III (n = 9) GBMs were multifocal in 11% and 29% of cases, respectively. Group I GBMs always had tumor recurrences noncontiguous with the initial lesion(s), while group IV GBM recurrences were always bordering the primary lesion. Group I GBMs may be most related to SVZ stem cells; these tumors were in intimate contact with the SVZ, were most likely to be multifocal at diagnosis, and recurred at great distances to the initial lesion(s). In contrast, group IV GBMs were always solitary lesions; these may arise from non-SVZ, white matter glial progenitors. Our MRI-based classification of GBMs may further our understanding of GBM histogenesis and help predict tumor recurrence pattern.

Key Words: glioblastoma multiforme (GBM) • MRI • neural stem cell • subventricular zone (SVZ) • tumor stem cell

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