**3. Primary vs. secondary GBM**

**Figure 2.** Gross Appearance of GBM

6 Tumors of the Central Nervous System – Primary and Secondary

**Figure 3.** Histological Appearance of Grade III Anaplastic Oligodendroglioma. [16]

shows mitotic figures at arrows and endothelial proliferation at asterisk. [16]

**Figure 4.** Histological Appearance of GBM. First Panel shows Pseudopalisading Nuclei at area of asterisk; second panel

Upon diagnosis, GBM is customarily delineated into one of two broad categories--Primary GBM, which arises *de novo* in brain tissue, or Secondary, which develops from lower grade astrocytomas (Refer to Table 2 for salient respective features and differences). In addition to the fundamental etiological difference, primary GBM possesses categorically different genetic and epigenetic differences from Secondary GBM. (Epigenetics refers to those meiotically or mitotically heritable traits resulting in phenotypic/gene expression patterns not related to changes in the underlying actual DNA code.) The vast majority of cases are GBM are primary, i.e*. de novo,* and comprise upwards of 90% of diagnosed cases. Epidemiologically, Primary GBMs are almost always found in the elderly population with a mean age of diagnosis of 62 years and is characterized by a rapidly inexorable course till death [27]. The genetic/epigenetic features that beget the malignant transformation in primary GBM and encompass its difference from secondary GBM include: mutations in and amplification of EGFR, loss of heterozygosity of Chromosome 10q, deletion of the phosphatase and tensin homologue (PTEN) on Chromo‐ some 10, and p16 deletion [16,23]. Secondary GBM, on the other hand, predominantly affects younger patients with a mean age at diagnosis of 45 years, and is characterized by a much slower, more smoldering course than Primary GBM [23]. Secondary GBM evolves from Grade II (Low Grade Well-Differentiated) and Grade III (Anaplastic) astrocytomas, has a predilection for the frontal lobes, and develops from its precursors over the course of years. An epidemio‐ logical study from 2005 showed that the time of progression from low-grade astrocytoma to GBM was approximately 5.3 years whereas the time of progression from anaplastic astrocy‐ toma to GBM was approximately 1.4 years [28]. This stands in stark contrast to the rapidity of Primary GBM progression, with roughly two-thirds of patients having a clinical history from time of diagnosis to death of less than 3 months [27]. As stated, secondary glioblastoma has a genetic/epigenetic footprint that differs from Primary GBM, the exception being the common‐ ality of loss of heterozygosity of Chromosome 10q. The differences in this epigenetic footprint include: mutations in p53, over expression of Platelet-Derived Growth Factor Receptor (PDGFR), aberrancies in p16/Retinoblastoma pathways, and global differences in transcription patterns and DNA copy numbers [16]. It is worthy of emphatic mention here that primary and secondary GBM, though developing through distinct genetic and molecular pathways, are grossly and histologically indistinguishable from one another.

Though there are no pathognomonic symptoms that may help the clinician to reliably distinguish between the two WHO Grades of malignant gliomas, there have been cohort

High Grade Glioma — Standard Approach, Obstacles and Future Directions

http://dx.doi.org/10.5772/58548

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Astrocytoma and Glioblastoma Multiforme (See Table 3). Prognostic factors boding favorably for patients diagnosed with malignant gliomas include a lower tumor grade, resection of tumor mass, younger age (less than 50 years) at time of diagnosis, higher performance status (e.g.

**Symptom Grade III, % Grade IV, %**

**Table 3.** Initial Symptoms in 565 Patients with Grade III or Grade IV Malignant Glioma (Data from Glioma Outcomes

The diagnostic modalities for suspected GBM in the appropriate clinical setting are, broadly, twofold: imaging and biopsy. The cornerstone of imaging is MRI with and without Gadolinium contrast enhancement. Prior to administration of contrast, malignant gliomas are hypo-intense on T1-weighted images (See Figure 5). Upon administration of Gadolinium, it is found that tumor enhances heterogeneously; this allows it to be distinguished from surrounding edema that remains hypo-intense on T-1 weighted images (See Figure 5). Another ancillary MRI submodality is FLAIR (Fluid Attenuated Inverse Reconstruction) MRI (See Figure 5) [30]. The utility of FLAIR MRI is that, as an inversion recovery MRI technique, it can essentially nullify or subtract the effects of fluid, thereby suppressing CSF in brain imaging. This can be especially useful in planning radiation therapy (to be discussed in more detail below) when it is of vital

importance to delineate malignancy from native vital brain parenchyma [31].

studies done that have shown some nuances in symptomatology between Anaplastic

Headache 53 57 Seizure 56 23 Memory Loss 26 39 Motor Weakness 25 36 Visual Symptoms 23 21 Language Deficits 22 36 Cognitive Changes 22 39 Personality Changes 11 27 Change in Consciousness 11 18 Nausea and Vomiting 8 15 Sensory Deficit 5 12 Papilledema 5 5

ECOG) score and intact neurological function [35].

Project [29])

**5. Diagnosis**


**Table 2.** Primary vs. Secondary GBM
