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induced systemic anti-tumor immune reactions distant tumor cells, e.g. Guerilla cells could be treated. Several mechanisms contribute therefore. Cells killed by PDT produce signals, increasing antigen presentation by dendric cells (DCs) and recruit antigen-specific cytotoxic

Great importance is also given to so called damage-associated molecular patterns (DAMPs). DAMPs are intracellular molecules in living cells, exposed by sudden cell damage as initialized for example by PDT. Up to date it is generally accepted that PDT activates the immune system. Complete understanding of the processes and how to influence them for improvement the immune responses is mandatory and could be advanced by closer

PDT for malignant gliomas is an interesting additional therapeutic tool with low side effects. By fundamentally distinct mechanisms compared to radiochemotherapy PDT also offers new opportunities for patients with tumor relapse. Hypericin seems to be a quite effective fluorescence marker for the detection of glioma. Since hypericin exhibits excellent photosensitizing properties, as demenostrated in detail *in vitro,* it might also be a promising PS in glioma therapy. Further *in vivo* investigations will proof this hypothesis in future. Due to high induction of apoptosis by hypericin mediated PDT, further investigations should focus on anti-tumor immunity by hypericin PDT, a chance to be more than only a local

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**11** 

*Germany* 

Jens Schittenhelm

*University of Tübingen,* 

**Diagnostic Evaluation of Diffuse Gliomas** 

 *Department of Neuropathology, Institute of Pathology and Neuropathology* 

Diffuse gliomas are preferentially located in the subcortical or deep white matter of the cerebral hemispheres and are the most frequent CNS neoplasms accounting for approximately 60 per cent of all CNS tumors (CBTRUS 2011). This definition excludes the circumscribed and biological different pilocytic astrocytoma and pilomyxoid astrocytoma which are covered in a separate chapter in this book. Other rare distinct glial neoplasms with a favourable prognosis such as the subependymal giant cell astrocytoma of lateral ventricles and the pleomorphic xanthoastrocytoma of children and young adults also do not belong into the group of diffuse gliomas. Ependymomas indeed are diffuse growing glial neoplasms but are biologically different. Moreover they appear in a different population as astrocytic and oligodendroglial neoplasms. Because of space limitations the current chapter deals only with astrocytomas, oligodendrogliomas, oligoastrocytomas and glioblastomas. These tumors are grouped here under the umbrella term "diffuse gliomas". They have a predilection for frontal and temporal lobes accounting together for more than two third of all cases. However diffuse astrocytomas may be seen in any other region of the brain

Although serious advances in neuroimaging of these brain tumors have been made in the past, histopathologic evaluation of neurosurgically removed tumor specimens is still required for definite diagnosis of diffuse gliomas. These CNS tumors show an extensive variety of histologcial and cytological appearance making diagnosis somewhat difficult for those who are not familiar in working with brain tumors. The current chapter focuses on neuropathological features of the different types of diffusely infiltrating gliomas based on the latest World Health Organization (WHO) classification of tumors of the nervous system. Core features and distinct pattern and variants are also introduced and illustrated. Immunohistochemistry and molecular biology have contributed to an improved classification and shown in some cases to be of prognostic value. The advantages and limitations of the most commonly used antibodies such as GFAP, WT1, MAP2, MIB-1, P53, IDH1R132H; NOGO-A are discussed in the current chapter. Molecular analysis of 1p19q codeletion, MGMT promoter methylation, Tp53 and isocitrate dehydrogenase mutations are

Regional incidences vary with generally higher number in developed countries and are estimated between 2.2 per million people for low-grade lesions (i.e. WHO grade II

including cerebellum and spinal cord (Louis et al., 2007a).

presented in detail and their implications are discussed.

**2. Incidence and overview** 

**1. Introduction** 

Uzdensky, A. B., Ma, L. W., Iani, V., Hjortland, G. O., Steen, H. B., & Moan, J. 2001, "Intracellular localisation of hypericin in human glioblastoma and carcinoma cell lines", *Lasers Med.Sci.*, vol. 16, no. 4, pp. 276-283.
