Brain Pathology Case of the Month - January 2007

FINAL DIAGNOSIS:   Diffuse high-grade glioma


The small volume of tissue samples in stereotactic biopsies complicates the differentiation between diffuse tumorous lesions and lesions of other pathogenesis. Apart from diffuse gliomas - due to the acuteness of clinical symptoms and the expansive, space-occupying character of the lesions - metastatic diseases, primary cerebral Non-Hodgkin's lymphomas, brain abscesses, parasitosis, ischemic brain tissue necrosis, or acute inflammatory demyelinisation (ADEM) may be suspected (3,4,7). In particular, the diffuse dissemination of atypical astrocyte-like cells with plump processes and the marked endothelial proliferation with only sporadical and scant perivasal inflammatory reaction led to the primary intraoperative diagnosis of a diffuse glioma in the presented case. However, only moderately increased cellularity, slight cytological atypia, and in particular, plenty of Creutzfeldt cells and "starburst" mitoses, which are typical findings in acute inflammatory demyelinating disease (1,2, 4,5,7), were confusing.

The pleomorphy and the hyperchromatic nuclei of GFAP positive cells, diminishment of axons, lack of clearly identifiable foamy cells, and the missing inflammatory reaction argued rather for a diffuse glioma than for a reactive/inflammatory lesion. The increased proliferative activity, necroses, and the marked endothelial proliferation, mostly with lack of perivascular inflammation made up the final diagnosis of a high-grade glioma.

Multinucleated astrocytes with micronuclei are a common, but not a specific phenomenon in acute demyelinating disease. They were first described and illustrated in detail by Creutzfeldt in 1923 (2). Another detailed neuropathological and clinical overview of ADEM and description of those "giant-cells" was given 1958 also by Peters (5). Creutzfeldt assigned those cells to glial elements and interpreted the appearance of multiple micronuclei or chromatin clumps as an effect of a deficient karyokinesis, which results from overwhelming reactive glial proliferation. Indeed, his hypothesis have been confirmed recently as cytomolecular investigations have shown, that micronuclei are induced in cytoplasm as a consequence of the formation of chromosomal fragments or remaining chromosomes during cell division by the causes of clastogens or aneugens (6). In practice, micronuclei are used in the mutagenicity research and as an indicator in genotoxicity screening tests.

In tumors, granular mitoses and Creutzfeldt cells are an uncommon finding, but the present case suggests that diagnostic application of those features should be careful, particularly in small biopsy samples.


  1. Burger PC, Scheithauer BW, Vogel SV (2002) Surgical Pathology of the Nervous System and its Coverings, 4th Edition, Churchill Livingstone: New York, Edinburgh, London, Philadelphia
  2. Creutzfeldt HG (1923) Zur Frage der sogenannten akuten multiplen Sklerose (Encephalomeyelitis disseminata non purulenta scleroticans acuta). Zugleich Mitteilung einer besonderen Entstehungsart von Riesenzellen. Arch Psych 68:485-517
  3. Hamilton RL (1997) Case of the month. September 1996 - new onset hemiparesis. Brain Pathol 7:715-716
  4. Niedermayer I, Deinzer M, Moringlane JR, Feiden W (2000) Neuropathological and neuroradiological aspects of acute disseminated encephalomyelitis (ADEM). Radiologe 40: 1030-1035
  5. Peters G (1958) Encephalomeyelitis disseminata non purulenta acuta (Akute multiple Sklerose). In: Handbuch der speziellen pathologischen Anatomie und Histologie, Lubarsch O, Henke F, R?ssle R (eds.), (volume 13) Nervensystem II, Bandteil A, Scholz W (ed.), pp.603-629, Springer: Berlin, Heidelberg, New-York
  6. Rosefort C, Fauth E, Zankl H (2004) Micronuclei induced by aneugens and clastogens in mononucleate and binucleate cells using the cytokinesis block assay. Mutagenesis 19: 277-284
  7. Zagzag D, Miller DC, Kleinman GM, Abati A, Donnenfeld H, Budzilovich GN (1993) Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis. Am J Surg Pathol 17:537-545


Dr. Bernd F.M. Romeike for editorial help and Prof. Dr. Wolfgang Reith and Christian Roth, Institute of Neuroradiology, University of the Saarland, Homburg/Saar, for providing the MRI figures.

Contributed by Yoo-Jin Kim, M.D. and Wolfgang Feiden, M.D.

International Society of Neuropathology