Journal of Neuro-Oncology

, Volume 140, Issue 2, pp 467–475 | Cite as

Clinical, neuroimaging and histopathological features of gliomatosis cerebri: a systematic review based on synthesis of published individual patient data

  • Marios K. Georgakis
  • Georgios Tsivgoulis
  • Dimitrios Spinos
  • Nikolaos G. Dimitriou
  • Athanasios P. Kyritsis
  • Ulrich Herrlinger
  • Eleni Th. Petridou
Clinical Study



Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating CNS tumor. As consistent disease features have not been established, the tumor comprises a diagnostic challenge.


We conducted a systematic literature search for published case reports and case series on patients with histologically confirmed GC. Clinical, diagnostic, neuroimaging, histopathological, and molecular data on individual or summary patient level were extracted and analyzed.


A total of 274 studies were identified, including 866 patients with individual-level data and 782 patients with summary data (58.9% males, mean age 43.6 years). Seizures (49.8%) were the most common presenting symptom followed by headache (35.9%), cognitive decline (32.2%), and focal motor deficits (32%). Imaging studies showed bilateral hemisphere involvement in 65%, infratentorial infiltration in 29.9% and a focal contrast-enhanced mass (type II GC) in 31.1% of cases. MRI (extensive hyperintensities in T2/FLAIR sequences) and MR spectroscopy (elevated choline, creatinine, and myoinositol levels; decreased NAA levels) showed highly consistent findings across GC patients. Low-grade and anaplastic astrocytoma were the most prevalent diagnostic categories, albeit features of any histology (astrocytic, oligodendroglial, oligoastrocytic) and grade (II–IV) were also reported. Among molecular aberrations, IDH1 mutation and MGMT promoter methylation were the most commonly reported. Increasing time elapsed from symptom onset to diagnosis comprised the only independent determinant of the extent of CNS infiltration.


A distinct clinical, neuroimaging, histopathological, or molecular GC phenotype is not supported by current evidence. MRI and MR spectroscopy are important tools for the diagnosis of the tumor before confirmation with biopsy.


Gliomatosis cerebri Glioma Diagnostics Clinical features Brain tumor 


Compliance with ethical standards

Conflict of interest

No author has anything to declare.

Supplementary material

11060_2018_2976_MOESM1_ESM.docx (327 kb)
Supplementary material 1 (DOCX 327 KB)


  1. 1.
    Ranjan S, Warren KE (2017) Gliomatosis cerebri: current understanding and controversies. Front Oncol 7:165. CrossRefGoogle Scholar
  2. 2.
    Greenfield JP, Castaneda Heredia A, George E, Kieran MW, Morales La Madrid A (2016) Gliomatosis cerebri: a consensus summary report from the First International Gliomatosis cerebri Group Meeting. Pediatr Blood Cancer 63:2072–2077. CrossRefGoogle Scholar
  3. 3.
    Herrlinger U (2012) Gliomatosis cerebri. Handb Clin Neurol 105:507–515. CrossRefGoogle Scholar
  4. 4.
    Yu A, Li K, Li H (2006) Value of diagnosis and differential diagnosis of MRI and MR spectroscopy in gliomatosis cerebri. Eur J Radiol 59:216–221. CrossRefGoogle Scholar
  5. 5.
    Ruda R, Bertero L, Sanson M (2014) Gliomatosis cerebri: a review. Curr Treat Options Neurol 16:273. CrossRefGoogle Scholar
  6. 6.
    Georgakis MK, Spinos D, Pourtsidis A, Psyrri A, Panourias IG, Sgouros S, Petridou ET (2018) Incidence and survival of gliomatosis cerebri: a population-based cancer registration study. J Neurooncol. Google Scholar
  7. 7.
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) World Health Organization histological classification of tumours of the central nervous system. Lyon, FranceGoogle Scholar
  8. 8.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. CrossRefGoogle Scholar
  9. 9.
    Broniscer A, Chamdine O, Hwang S, Lin T, Pounds S, Onar-Thomas A, Shurtleff S, Allen S, Gajjar A, Northcott P, Orr BA (2016) Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas. Acta Neuropathol 131:299–307. CrossRefGoogle Scholar
  10. 10.
    Herrlinger U, Jones DTW, Glas M, Hattingen E, Gramatzki D, Stuplich M, Felsberg J, Bahr O, Gielen GH, Simon M, Wiewrodt D, Schabet M, Hovestadt V, Capper D, Steinbach JP, von Deimling A, Lichter P, Pfister SM, Weller M, Reifenberger G (2016) Gliomatosis cerebri: no evidence for a separate brain tumor entity. Acta Neuropathol 131:309–319. CrossRefGoogle Scholar
  11. 11.
    Carroll KT, Hirshman B, Ali MA, Alattar AA, Brandel MG, Lochte B, Lanman T, Carter B, Chen CC (2017) Management and survival patterns of patients with gliomatosis cerebri: a SEER-based analysis. World Neurosurg 103:186–193. CrossRefGoogle Scholar
  12. 12.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefGoogle Scholar
  13. 13.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. CrossRefGoogle Scholar
  14. 14.
    Glas M, Bahr O, Felsberg J, Rasch K, Wiewrodt D, Schabet M, Simon M, Urbach H, Steinbach JP, Rieger J, Fimmers R, Bamberg M, Nagele T, Reifenberger G, Weller M, Herrlinger U, Neuro-Oncology Group of the German Cancer S (2011) NOA-05 phase 2 trial of procarbazine and lomustine therapy in gliomatosis cerebri. Ann Neurol 70:445–453. CrossRefGoogle Scholar
  15. 15.
    Skerman HM, Yates PM, Battistutta D (2012) Identification of cancer-related symptom clusters: an empirical comparison of exploratory factor analysis methods. J Pain Symptom Manage 44:10–22. CrossRefGoogle Scholar
  16. 16.
    Almutary H, Douglas C, Bonner A (2016) Multidimensional symptom clusters: an exploratory factor analysis in advanced chronic kidney disease. J Adv Nurs 72:2389–2400. CrossRefGoogle Scholar
  17. 17.
    Hanwella R, de Silva VA (2011) Signs and symptoms of acute mania: a factor analysis. BMC Psychiatry 11:137. CrossRefGoogle Scholar
  18. 18.
    Bourne TD, Schiff D (2010) Update on molecular findings, management and outcome in low-grade gliomas. Nat Rev Neurol 6:695–701. CrossRefGoogle Scholar
  19. 19.
    Boots-Sprenger SH, Sijben A, Rijntjes J, Tops BB, Idema AJ, Rivera AL, Bleeker FE, Gijtenbeek AM, Diefes K, Heathcock L, Aldape KD, Jeuken JW, Wesseling P (2013) Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution. Mod Pathol 26:922–929. CrossRefGoogle Scholar
  20. 20.
    Masui K, Cloughesy TF, Mischel PS (2012) Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathol Appl Neurobiol 38:271–291. CrossRefGoogle Scholar
  21. 21.
    Guzman-de-Villoria JA, Sanchez-Gonzalez J, Munoz L, Reig S, Benito C, Garcia-Barreno P, Desco M (2007) 1H MR spectroscopy in the assessment of gliomatosis cerebri. AJR Am J Roentgenol 188:710–714. CrossRefGoogle Scholar
  22. 22.
    Bendszus M, Warmuth-Metz M, Klein R, Burger R, Schichor C, Tonn JC, Solymosi L (2000) MR spectroscopy in gliomatosis cerebri. AJNR Am J Neuroradiol 21:375–380Google Scholar
  23. 23.
    Georgakis MK, Karalexi MA, Kalogirou EI, Ryzhov A, Zborovskaya A, Dimitrova N, Eser S, Antunes L, Sekerija M, Zagar T, Bastos J, Agius D, Florea M, Coza D, Bouka E, Bourgioti C, Dana H, Hatzipantelis E, Moschovi M, Papadopoulos S, Sfakianos G, Papakonstantinou E, Polychronopoulou S, Sgouros S, Stefanaki K, Stiakaki E, Strantzia K, Zountsas B, Pourtsidis A, Patsouris E, Petridou ET (2017) Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US. J Neurooncol 131:163–175. CrossRefGoogle Scholar
  24. 24.
    Taillibert S, Chodkiewicz C, Laigle-Donadey F, Napolitano M, Cartalat-Carel S, Sanson M (2006) Gliomatosis cerebri: a review of 296 cases from the ANOCEF database and the literature. J Neurooncol 76:201–205. CrossRefGoogle Scholar
  25. 25.
    Shimony N, Shofty B, Ram Z, Grossman R (2017) Perioperative risk assessment of patients with gliomatosis cerebri. World Neurosurg 98:334–338. CrossRefGoogle Scholar
  26. 26.
    Chen S, Tanaka S, Giannini C, Morris J, Yan ES, Buckner J, Lachance DH, Parney IF (2013) Gliomatosis cerebri: clinical characteristics, management, and outcomes. J Neurooncol 112:267–275. CrossRefGoogle Scholar
  27. 27.
    Kaloshi G, Guillevin R, Martin-Duverneuil N, Laigle-Donadey F, Psimaras D, Marie Y, Mokhtari K, Hoang-Xuan K, Delattre JY, Sanson M (2009) Gray matter involvement predicts chemosensitivity and prognosis in gliomatosis cerebri. Neurology 73:445–449. CrossRefGoogle Scholar
  28. 28.
    Kim K, Chie EK, Park HJ, Kim DG, Jung HW, Park SH, Kim IH (2014) Exclusive radiotherapy for gliomatosis cerebri: long-term follow-up at a single institution. Clin Transl Oncol 16:829–833. CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Second Department of Neurology, “Attikon” University Hospital, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of NeurologyUniversity of Tennessee Health Science CenterMemphisUSA
  4. 4.Department of Neurology, University Hospital of Ioannina, Medical SchoolUniversity of IoanninaIoanninaGreece
  5. 5.Division of Neurooncology, Department of NeurologyUniversity Medical Center BonnBonnGermany
  6. 6.Unit of Clinical EpidemiologyKarolinska InstituteStockholmSweden

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