Definition and Diagnostic Implications of Gemistocytic Astrocytomas: A Pathological Perspective


Gemistocytic astrocytoma still continues to be enigmatic; both in terms of definition and prognostic implications. The major issue of contention has been the clinical relevance of this pathological entity. The currently accepted definition of gemistocytic astrocytoma requires 20% or more gemistocytes, and considers the neoplasm as a diffuse astrocytoma, which is a WHO grade II tumor. Some suggest that gemistocytic morphology should be considered as evidence of a higher grade astrocytoma. However, there is no consensus on the percentage of gemistocytes associated with a worse prognosis than otherwise expected. Given the reported cases and series, it is not clear that this morphology portends a more aggressive biology when all else is equal. There is still a need for studies with sufficient numbers of well-matched gemistocytic and non-gemistocytic astrocytic neoplasms to decide whether upgrading a tumor with ‘significant’ number of gemistocytes is justifiable. This article presents a critical review of the existing studies and a brief mention of our experience from a pathological perspective.

This is a preview of subscription content, access via your institution.


  1. 1.

    P Kleihues WKe Cavenee (2000) Pathology and Genetics of Tumours of the Nervous System. World Health Organization Classification of Tumours IARC Press Lyon

    Google Scholar 

  2. 2.

    JM Kros N Waarsenburg DP Hayes WC Hop H Dekken Particlevan (2000) ArticleTitleCytogenetic analysis of gemistocytic cells in gliomas J Neuropathol Exp Neurol 59 679–86 Occurrence Handle1:STN:280:DC%2BD3cvhtl2itw%3D%3D Occurrence Handle10952058

    CAS  PubMed  Google Scholar 

  3. 3.

    K Abe H Hasegawa Y Kobayashi H Fujimura S Yorifuji S Bitoh (1990) ArticleTitleA gemistocytic astrocytoma demonstrated high intensity on MR images Protein hydration layer Neuroradiology 32 166–7 Occurrence Handle1:STN:280:By%2BA2sjjsFQ%3D Occurrence Handle2398944

    CAS  PubMed  Google Scholar 

  4. 4.

    HG Krouwer RL Davis P Silver M Prados (1991) ArticleTitleGemistocytic astrocytomas: a reappraisal J Neurosurg 74 399–406 Occurrence Handle1:STN:280:By6C3s3is1c%3D Occurrence Handle1993905

    CAS  PubMed  Google Scholar 

  5. 5.

    Y Okamoto PL Patre ParticleDi C Burkhard S Horstmann B Jourde M Fahey D Schuler NM Probst-Hensch MG Yasargil Y Yonekawa UM Lutolf P Kleihues H Ohgaki (2004) ArticleTitlePopulation-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas Acta Neuropathol (Berl) 108 49–56

    Google Scholar 

  6. 6.

    EG Shaw C Daumas-Duport BW Scheithauer DT Gilbertson JR O’Fallon JD Earle ER Laws SuffixJr. H Okazaki (1989) ArticleTitleRadiation therapy in the management of low-grade supratentorial astrocytomas J Neurosurg 70 853–61 Occurrence Handle1:STN:280:BiaB3srnt1Q%3D Occurrence Handle2715812

    CAS  PubMed  Google Scholar 

  7. 7.

    L Westergaard F Gjerris L Klinken (1993) ArticleTitlePrognostic parameters in benign astrocytomas Acta Neurochir (Wien) 123 1–7 Occurrence Handle10.1007/BF01476278 Occurrence Handle1:STN:280:ByuD38nktF0%3D

    Article  CAS  Google Scholar 

  8. 8.

    F Nissl (1904) ArticleTitleZur histopathologie der paralytischen Rindenerkrankung Histol Histopathol Arb Grosshirn 1 315

    Google Scholar 

  9. 9.

    DS Russell LJ Rubinstein (1989) Pathology of Tumors of the Nervous System Williams & Wilkins Baltimore 111–114

    Google Scholar 

  10. 10.

    P Kleihues RL Davis H Ohgaki PC Burger MM Westphal WK Cavenee (2000) Diffuse astrocytoma P Kleihues WK Cavenee (Eds) Pathology and Genetics of Tumors of the Nervous System IARC Press Lyon 22–26

    Google Scholar 

  11. 11.

    KJ Zulch (1957) The Astrocytomas, Brain Tumors, Their Biology and Pathology Springer Publishing Co New York 160–167

    Google Scholar 

  12. 12.

    KJ Zulch (1979) Histological Typing of Tumours of the Central Nervous System World Health Organization Geneva

    Google Scholar 

  13. 13.

    P Kleihues PC Burger BW Scheithauer (1993) Histological Typing of Tumours of the Central Nervous System Springer-Verlag Berlin

    Google Scholar 

  14. 14.

    AR Elvidge A Martinez-Coll (1956) ArticleTitleLong-term follow-up of 106 cases of astrocytom 1928–1939 J Neurosurg 13 230–43 Occurrence Handle1:STN:280:CymD1Mbht1c%3D Occurrence Handle13346399

    CAS  PubMed  Google Scholar 

  15. 15.

    S Kosel BW Scheithauer MB Graeber (2001) ArticleTitleGenotype-phenotype correlation in gemistocytic astrocytomas Neurosurgery 48 187–93 Occurrence Handle1:STN:280:DC%2BD3M7jvVamsw%3D%3D Occurrence Handle11152345

    CAS  PubMed  Google Scholar 

  16. 16.

    HJ Yang JE Kim SH Paek JG Chi HW Jung DG Kim (2003, ) ArticleTitleThe significance of gemistocytes in astrocytoma Acta Neurochir (Wien) 145 1097–103 Occurrence Handle10.1007/s00701-003-0149-4 Occurrence Handle1:STN:280:DC%2BD3srotFGitg%3D%3D

    Article  CAS  Google Scholar 

  17. 17.

    D Naidoo (1955) ArticleTitleGemistocytic astrocytoma: cytological observations on the rate of hydrolysis of some phosphoric acid esters Acta Psychiatr Neurol Scand 30 499–506 Occurrence Handle1:CAS:528:DyaG2MXosFOnsA%3D%3D Occurrence Handle13301910

    CAS  PubMed  Google Scholar 

  18. 18.

    T Hoshino BC Wilson WG Ellis (1975) ArticleTitleGemistocytic astrocytes in gliomas. An autoradiographic study J Neuropathol Exp Neurol 34 263–81 Occurrence Handle1:STN:280:CSqC1M7htlQ%3D Occurrence Handle167133

    CAS  PubMed  Google Scholar 

  19. 19.

    F Giangaspero PC Burger (1983) ArticleTitleCorrelations between cytologic composition and biologic behavior in the glioblastoma multiforme. A postmortem study of 50 cases Cancer 52 2320–33 Occurrence Handle1:STN:280:BiuD2MvpvFQ%3D Occurrence Handle6315212

    CAS  PubMed  Google Scholar 

  20. 20.

    JM Kros SZ Stefanko AA Jong Particlede CC Vroonhoven Particlevan RO Heul Particlevan der TH Kwast Particlevan der (1991) ArticleTitleUltrastructural and immunohistochemical segregation of gemistocytic subsets Hum Pathol 22 33–40 Occurrence Handle1:STN:280:By6D1crptlI%3D Occurrence Handle1985075

    CAS  PubMed  Google Scholar 

  21. 21.

    PC Burger B Scheithauer FS Vogel (2002) The Brain-Tumors, Surgical Pathology of the Nervous System and Its Coverings Churchill Livingstone Philadelphia 160–378

    Google Scholar 

  22. 22.

    A Ridley JB Cavanagh (1971) ArticleTitleLymphocytic infiltration in gliomas: evidence of possible host resistance Brain 94 117–24 Occurrence Handle1:STN:280:CS6C2MbgsFI%3D Occurrence Handle5552158

    CAS  PubMed  Google Scholar 

  23. 23.

    DK Boker R Kalff F Gullotta S Weekes-Seifert U Mohrer (1984) ArticleTitleMononuclear infiltrates in human intracranial tumors as a prognostic factor. Influence of preoperative steroid treatment. I. Glioblastoma Clin Neuropathol 3 143–7 Occurrence Handle1:STN:280:BiqD3c3ktlM%3D Occurrence Handle6478676

    CAS  PubMed  Google Scholar 

  24. 24.

    J Takeuchi RO Barnard (1976) ArticleTitlePerivascular lymphocytic cuffing in astrocytomas Acta Neuropathol (Berl) 35 265–71 Occurrence Handle1:STN:280:CSmB2cbkt1w%3D

    CAS  Google Scholar 

  25. 25.

    PC Burger FS Vogel SB Green TA Strike (1985) ArticleTitleGlioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications Cancer 56 1106–11 Occurrence Handle1:STN:280:BiqB2Mvjt1E%3D Occurrence Handle2990664

    CAS  PubMed  Google Scholar 

  26. 26.

    K Watanabe O Tachibana Y Yonekawa P Kleihues H Ohgaki (1997) ArticleTitleRole of gemistocytes in astrocytoma progression Lab Invest 76 277–84 Occurrence Handle1:STN:280:ByiC1Mvnt1I%3D Occurrence Handle9042164

    CAS  PubMed  Google Scholar 

  27. 27.

    KH Fulling DM Garcia (1985) ArticleTitleAnaplastic astrocytoma of the adult cerebrum. Prognostic value of histologic features Cancer 55 928–31 Occurrence Handle1:STN:280:BiqD1MfpvVM%3D Occurrence Handle3967200

    CAS  PubMed  Google Scholar 

  28. 28.

    A Perry RB Jenkins JR O’Fallon PL Schaefer DW Kimmel MR Mahoney BW Scheithauer SM Smith EM Hill TJ Sebo R Levitt J Krook LK Tschetter RF Morton JC Buckner (1999) ArticleTitleClinicopathologic study of 85 similarly treated patients with anaplastic astrocytic tumors. An analysis of DNA content (ploidy), cellular proliferation, and p53 expression Cancer 86 672–83 Occurrence Handle10.1002/(SICI)1097-0142(19990815)86:4<672::AID-CNCR17>3.0.CO;2-G Occurrence Handle1:STN:280:DyaK1MzmvFOmuw%3D%3D Occurrence Handle10440696

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    DC Martins JN Stavale SM Malheiros LH Santiago LC Roman KC Aguiar (2001) ArticleTitle[Fraction of gemistocytic astrocytes and immunoexpression of p53 protein in astrocytomas grade II and III (WHO)] Arq Neuropsiquiatr 59 926–31 Occurrence Handle1:STN:280:DC%2BD3Mnos12ksw%3D%3D Occurrence Handle11733839

    CAS  PubMed  Google Scholar 

  30. 30.

    JM Kros WC Schouten PJ Janssen TH Kwast Particlevan der (1996) ArticleTitleProliferation of gemistocytic cells and glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells in gliomas: a MIB-1/GFAP double labeling study Acta Neuropathol (Berl) 91 99–103 Occurrence Handle1:STN:280:BymA28bhsVI%3D

    CAS  Google Scholar 

  31. 31.

    M Ogashiwa M Nakadai Y Asoh T Maeda H Yokoyama K Takeuchi S Uchigasaki K Akai (1987) ArticleTitle[Morphological analysis of recurrent gliomas. Giant cell and gemistocytic cell formation] Neurol Med Chir (Tokyo) 27 276–82 Occurrence Handle1:STN:280:BieD28nit1A%3D Occurrence Handle10.2176/nmc.27.276

    CAS  Article  Google Scholar 

  32. 32.

    EW Newcomb SK Bhalla CL Parrish RL Hayes H Cohen DC Miller (1997) ArticleTitleBcl-2 protein expression in astrocytomas in relation to patient survival and p53 gene status Acta Neuropathol (Berl) 94 369–75 Occurrence Handle1:CAS:528:DyaK2sXlvFCnu7g%3D

    CAS  Google Scholar 

  33. 33.

    K Onda RL Davis CB Wilson T Hoshino (1994) ArticleTitleRegional differences in bromodeoxyuridine uptake, expression of Ki-67 protein, and nucleolar organizer region counts in glioblastoma multiforme Acta Neuropathol (Berl) 87 586–93 Occurrence Handle1:CAS:528:DyaK2cXlslKgu7c%3D

    CAS  Google Scholar 

  34. 34.

    MB Lopes HJ Altermatt BW Scheithauer CW Shepherd SR VandenBerg (1996) ArticleTitleImmunohistochemical characterization of subependymal giant cell astrocytomas Acta Neuropathol (Berl) 91 368–75 Occurrence Handle1:STN:280:BymB2MvivVI%3D

    CAS  Google Scholar 

  35. 35.

    SZ Powell AT Yachnis LB Rorke AM Rojiani TA Eskin (1996) ArticleTitleDivergent differentiation in pleomorphic xanthoastrocytoma. Evidence for a neuronal element and possible relationship to ganglion cell tumors Am J Surg Pathol 20 80–5 Occurrence Handle10.1097/00000478-199601000-00009 Occurrence Handle1:STN:280:BymC3s%2Fit1E%3D Occurrence Handle8540612

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    K Watanabe A Peraud C Gratas S Wakai P Kleihues H Ohgaki (1998) ArticleTitlep53 and PTEN gene mutations in gemistocytic astrocytomas Acta Neuropathol (Berl) 95 559–64 Occurrence Handle1:CAS:528:DyaK1cXislWmtbo%3D

    CAS  Google Scholar 

  37. 37.

    RM Reis A Hara P Kleihues H Ohgaki (2001) ArticleTitleGenetic evidence of the neoplastic nature of gemistocytes in astrocytomas Acta Neuropathol (Berl) 102 422–5 Occurrence Handle1:CAS:528:DC%2BD3MXotFSiur8%3D

    CAS  Google Scholar 

  38. 38.

    W Paulus C Grothe M Sensenbrenner T Janet I Baur M Graf W Roggendorf (1990) ArticleTitleLocalization of basic fibroblast growth factor, a mitogen and angiogenic factor, in human brain tumors Acta Neuropathol (Berl) 79 418–23 Occurrence Handle1:STN:280:By%2BB2M3lsF0%3D

    CAS  Google Scholar 

  39. 39.

    DF Stefanik LR Rizkalla A Soi SA Goldblatt WM Rizkalla (1991) ArticleTitleAcidic and basic fibroblast growth factors are present in glioblastoma multiforme and normal brain Ann N Y Acad Sci 638 477–80 Occurrence Handle1:CAS:528:DyaK38XkvVOks7Y%3D Occurrence Handle1723863

    CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Tarik Tihan.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tihan, T., Vohra, P., Berger, M.S. et al. Definition and Diagnostic Implications of Gemistocytic Astrocytomas: A Pathological Perspective. J Neurooncol 76, 175–183 (2006).

Download citation


  • astrocytoma
  • classification
  • gemistocytic
  • glioma
  • pathology
  • review