**4.2. Histopathology**

Gliomas constitute a heterogeneous group of primary central nervous system tumors. The term astrocytoma includes tumors with astrocytic differentiation. They may have a wide spectrum of cell types in pure or mixed form. The classical tumor cells may show elongated, irregular hyperchromatic nuclei, often with no discernible cytoplasm, and embedded in a dense fibrillary matrix, mixed with cells that display visible eosinophilic cytoplasmic processes. However,cellular diversity, such as gemistocytic cell, protoplasmic cell, sarcomatous cell, epitheliod cell, granular cell, giant cell, or small cell is eventually observed. Glioblastoma display microvascular hyperplasia and tumor necrosis (pseudopalisading areas or infarct-like areas) [11, 12] (**Figure 2**).

**4.3. The 2016 World Health Organization classification of tumors of the central** 

According to the 2016 World Health Organization classification of tumors of the central nervous system [13], the diffuse gliomas include the WHO grade II and grade III astrocytic tumors, the grade II and III oligodendrogliomas, the grade IV glioblastomas, as well as the related diffuse gliomas of childhood. Then, all diffusely infiltrating gliomas (whether astrocytic or oligodendroglial) are grouped together: based not only on their growth pattern and behaviors but also more pointedly on the shared genetic driver mutations in the *IDH1* and *IDH2* genes. This approach leaves those astrocytomas that have a more circumscribed growth pattern, lack IDH gene family alterations, and frequently have *BRAF* alterations (pilocytic astrocytoma, pleomorphic xanthoastrocytoma) or *TSC1*/*TSC2* mutations (subependymal giant cell astrocytoma) distinct from the dif-

Functional and Therapeutic Implications of Mitochondrial Network and Mitochondria…

http://dx.doi.org/10.5772/intechopen.77224

17

The WHO grade II diffuse astrocytomas and WHO grade III anaplastic astrocytomas are now each divided into IDH-mutant, IDH-wildtype, and NOS categories. It is recommended that WHO grading is retained for both IDH-mutant and IDH-wildtype astrocytomas, although the prognosis of the IDH-mutant cases appears more favorable in

Glioblastomas are divided into: (1) glioblastoma, IDH-wildtype (about 90% of cases), which corresponds most frequently with the clinically defined primary or de novo glioblastoma and predominates in patients over 55 years of age [14]; (2) glioblastoma, IDH-mutant (about 10% of cases), which corresponds closely to so-called secondary glioblastoma with a history of prior lower grade diffuse glioma and preferentially arises in younger patients [14];and (3) glioblastoma, NOS, a diagnosis that is reserved for those tumors for which full IDH

Today, gliomas still represent a serious and discouraging brain tumor; despite the diversity of treatment modalities, generally, the prognosis for patients is still poor (i.e., fatality and sequelae). Even with surgical resection and aggressive treatment with chemotherapy and

radiotherapy, the prognosis for patients with astrocytomas remains very poor [15].

**glioma ultrastructural pathology, and their functional and** 

bolic and Ca2+ buffering needs, or in response to different cellular insults [16].

**6. The mitochondrial network, mitochondria-associated membranes,** 

Both the endoplasmic reticulum and mitochondria are highly dynamic organelles, forming networks that may undergo rapid changes in the size, length, and shape, depending on meta-

**nervous system**

fuse gliomas.

both grades.

evaluation cannot be performed.

**therapeutic implications**

**5. Biologic behavior**

The infiltrative or diffuse forms of astrocytoma are composed of individual tumor cells that infiltrate widely throughout the brain parenchyma with a cellular density and degree of anaplasia that increase with tumor grade. They are characterized by invasive growth such that nonneoplastic cells are often intermixed and may even predominate in some areas. The secondary structures of Scherer include subpial condensation, perineuronal satellitosis, and perivascular aggregation. The extreme end of the infiltrative spectrum, previously assigned as gliomatosis cerebri; it involves multiples lobes of the brain, often bilaterally and frequently extending into the brain stem, cerebellum, and even the spinal cord [11, 12].

**Figure 2.** Histopathology. (A) Diffuse astrocytoma. Tumor cells show elongated, irregular hyperchromatic nuclei, with no discernible cytoplasm and embedded in a dense fibrillary matrix, mixed with cells that display visible eosinophilic cytoplasmic processes. (B) Glioblastoma displays a hypercellular-solid neoplasm with fuzzy or ill-defined margins, with diffuse parenchymal infiltration. (C) Glioblastoma: a pseudopalisading necrosis area. (D) Glioblastoma: an epitheliod-like cell area. (E) Glioblastoma: hypercellularity, tumor cells show elongated, irregular hyperchromatic nuclei, with no discernible cytoplasm and embedded in a dense fibrillary matrix, mixed with cells that display visible eosinophilic cytoplasmic processes. (F and G) Glioblastoma: cooption blood vessels surrounded by tumor gemistocytic cells. (H) Glioblastoma displaying microvascular hyperplasia. (I) Giant-cell glioblastoma corresponding to **Figure 1C**.
