Cent Eur Neurosurg 2010; 71(1): 20-25
DOI: 10.1055/s-0029-1241190
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Multicentric Tumor Manifestations of High Grade Gliomas: Independent Proliferation or Hallmark of Extensive Disease?

M. Hefti1 , G. von Campe2 , C. Schneider3 , U. Roelcke4
  • 1UKSH, Neurosurgery, Kiel, Germany
  • 2Universitätslinik Graz, Neurosurgery, Graz, Austria
  • 3Kantonsspital Winterthur, Neurosurgery, Winterthur, Switzerland
  • 4Kantonsspital Aarau, Neurology, Aarau, Switzerland
Further Information

Publication History

Publication Date:
19 February 2010 (online)

Abstract

Objective: Improvements in microneurosurgical techniques, radiotherapy and chemotherapy for the treatment of high grade gliomas resulted in better local tumor control and longer progression-free survival. Multicentric (MC) lesions located distant from the initial resection area contribute to treatment failure in a growing number of patients. These MC lesions may develop within the course of the disease (metachronous) or may already be present at the time of first tumor manifestation (synchronous). To look for mechanisms and regular patterns behind MC glioma manifestations and to investigate whether they are “a second primary tumor” or the result of continuous diffuse glioblastoma cell invasion, we retrospectively analyzed the initial and all follow-up MR studies of our high grade glioma (HGG) patients.

Patients and Methods: MR studies of 247 consecutive patients treated for HGG at a single institution were analyzed. MC tumor manifestation was defined as more than one gadolinium enhancing lesion within the brain on MRI without a connecting signal alteration in T2 sequences and/or without a connecting hypointense mass in T1 sequences. The minimal distance to define two solitary lesions was set at >10 mm. According to these specifications 40 patients showed MC tumor manifestations in their MR studies on admission or during treatment of their disease. The MR studies of these cases were retrospectively analyzed for patterns in MC tumor manifestation and progression. Topographical specifications and delay in manifestation were used to explain possible pathways of development. Kaplan Meyer survival graphs for metachronous and synchronous MC disease were calculated.

Results: 24 patients showed MC tumor manifestation at the time of admission. 16 cases developed MC manifestation within a follow-up period of 3–57 months. The location of all lesions could be categorized into one of three distinct patterns (white matter, subependymal, intraventricular). The patterns showed individual and location-specific time gaps to metachronous manifestation. Calculated from the time of first tumor diagnosis, the median survival was longer for patients with metachronous MC lesions (353 days, p<0.05) compared to patients with synchronous MC lesions (110 days) or patients without multicentricity (234 days). Patients with metachronous lesions showed a similar survival (72 days) as patients with synchronous MC lesions (110 days) once they developed MC disease.

Conclusion: The topographical patterns and temporal characteristics of MC disease suggest that all manifestations share common mechanisms such as an active migratory process. Our data therefore do not support the concept of an independent MC development of multiple gliomas.

Literatur

  • 1 Abbott NJ. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology.  Neurochem Int. 2004;  45 545-552
  • 2 Arita N, Taneda M, Hayakawa T. Leptomeningeal dissemination of malignant gliomas. Incidence, diagnosis and outcome.  Acta Neurochir (Wien). 1994;  126 84-92
  • 3 Barnard RO, Geddes JF. The incidence of multifocal cerebral gliomas. A histologic study of large hemisphere sections.  Cancer. 1987;  60 1519-1531
  • 4 Batzdorf U, Malamud N. The problem of multicentric gliomas.  J Neurosurg. 1963;  20 122-136
  • 5 Borovich B, Mayer M, Gellei B. et al . Multifocal glioma of the brain. Case report.  J Neurosurg. 1976;  45 229-232
  • 6 Berens ME, Giese A. “…those left behind”. Biology and oncology of invasive glioma cells.  Neoplasia. 1999;  1 208-219
  • 7 Bradley WL. Case of gliosarcomatous tumors of the brain.  Proc Conn Med Soc. 1880;  2 39-41
  • 8 Budka H, Podreka I, Reisner T. et al . Diagnostic and pathomorphological aspects of glioma multiplicity.  Neurosurg Rev. 1980;  3 233-241
  • 9 Chadduck WM, Roycroft D, Brown MW. Multicentric glioma as a cause of multiple cerebral lesions.  Neurosurgery. 1983;  13 170-175
  • 10 Dandy WE. Removal of the right hemisphere for certain tumours with hemiplegia: preliminary report.  J Am Med Assoc. 1928;  90 823-825
  • 11 Djalilian HR, Shah MV, Hall WA. Radiographic incidence of multicentric malignant gliomas.  Surg Neurol. 1999;  51 554-557
  • 12 Gaspar LE, Fisher BJ, Macdonald DR. et al . Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment.  Int J Radiat Oncol Biol Phys. 1992;  24 55-57
  • 13 Geer CP, Grossman SA. Interstitial fluid flow along white matter tracts: a potentially important mechanism for the dissemination of primary brain tumors.  J Neurooncol. 1997;  32 193-201
  • 14 Giese A, Westphal M. Glioma invasion in the central nervous system.  Neurosurgery. 1996;  39 235-250
  • 15 Giese A. Glioma invasion–pattern of dissemination by mechanisms of invasion and surgical intervention, pattern of gene expression and its regulatory control by tumorsuppressor p53 and proto-oncogene ETS-1.  Acta Neurochir Suppl. 2003;  88 153-162
  • 16 Globus J KH. The subependymal cell plate (matrix) and its relationship to brain tumors of the ependymal type.  J Neuropathol Exp Neurol. 2006;  3 1-35
  • 17 Gowers WR. Manual of Diseases of the Nervous System.  Philadelphia: P Blakiston, Son & Co. 1896; 
  • 18 Hartmann M, Jansen O, Egelhof T. et al . Effect of brain edema on the recurrence pattern of malignant gliomas.  Radiologe. 1998;  38 948-953
  • 19 Hirschmann-Jax C, Foster AE, Wulf GG. et al . A distinct “side population” of cells with high drug efflux capacity in human tumor cells.  PNAS. 2004;  101 14228-14233
  • 20 Krex D, Mohr B, Appelt H. et al . Genetic analysis of a multifocal glioblastoma multiforme: a suitable tool to gain new aspects in glioma development.  Neurosurgery. 2003;  53 1377-1384
  • 21 Kutsi K, Soner Y, Nezi M. et al . Magnetic resonance imaging findings of multicentric glioma.  The Medical Journal of Kocatepe. 2006;  5 55-57
  • 22 Kyritsis AP, Levin VA, Yung WK. et al . Imaging patterns of multifocal gliomas.  Eur J Radiol. 1993;  16 163-170
  • 23 Lim DA, Cha S, Mayo MC. et al . Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype.  Neuro-Oncology. 2007;  9 424-429
  • 24 Noctor SC, Flint AC, Weissman TA. et al . Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia.  J Neurosci. 2002;  22 3161-3173
  • 25 Onda K, Tanaka R, Takahashi H. et al . Cerebral glioblastoma with cerebrospinal fluid dissemination: a clinicopathological study of 14 cases examined by complete autopsy.  Neurosurgery. 1989;  25 533-540
  • 26 Reis RM, Herva R, Brandner S. et al . Second primary glioblastoma.  J of Neuropathology and Experimental Neurology. 2001;  60 ((2)) 208-215
  • 27 Reya T, Morrison SJ, Clarke MF. et al . Stem cells, cancer, and cancer stem cells.  Nature. 2001;  414 105-111
  • 28 Sanai N, Varez-Buylla A, Berger MS. Neural stem cells and the origin of gliomas.  NEJM. 2005;  353 811-822
  • 29 Scherer HJ. The forms of growth in gliomas and their practical significance.  Brain. 1940;  63 1-35
  • 30 van Nifterik KA, Elkhuizen PH, van Andel RJ. et al . Genetic profiling of a distant second glioblastoma multiforme after radiotherapy: recurrence or second primary tumor?.  J Neurosurg. 2006;  105 739-744
  • 31 Willis RA. Pathology of Tumors. London: Butterworths; 1960 : 811
  • 32 Zakrzewska M, Szybka M, Biernat W. et al . Diverse molecular pattern in a bihemispheric glioblastoma (butterfly glioma) in a 16-year-old boy.  Cancer Genetics and Cytogenetics. 2007;  177 125-130

Korrespondenzadresse

Dr. Martin Hefti

UKSH, Neurosurgery

Schittenhelmstraße 10

24105 Kiel

Germany

Phone: 431/597/48 11

Fax: 431/597/48 31

Email: heftim@nch.uni-kiel.de