**Grading**. Grade II WHO.

**Clinical presentation**. The classical presentation of a patient with oligodendroglioma is with seizures that precede with years and with other neurological signs like mental disturbances, neurological deficits, or signs of increased intracranial pressure (mostly headache). Even in patients with no seizures at the onset, they will develop such clinical manifestations during the course of disease. The brutal debut due to an intratumoral hemorrhage although rare, is more frequent in oligodendrogliomas than in other low-grade gliomas [62].

**Imaging**. *CT scan* is usually the first imagistic tool in emergency, and for more than 50% of oligodendrogliomas that present intratumoral calcification, it is a useful diagnostic method. On CT scan, oligodendrogliomas are present as well-delineated cortical-based hypodense lesion with intratumoral or peripheral calcification. Cystic component are not rare and hemorrhagic regions may also be encountered (**Figure 6**). Contrast enhancement is absent or marginal. Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management http://dx.doi.org/10.5772/intechopen.76205 105

*2.2.1. Multimodal treatment*

104 Glioma - Contemporary Diagnostic and Therapeutic Approaches

*2.2.1.1. Surgical treatment*

*2.2.1.2. Adjuvant treatment*

**2.3. Diffuse astrocytoma NOS**

**Grading**. Grade II WHO.

determined.

gliomas [62].

and oral administration, is superior or not to PCV [61].

**2.4. Oligodendroglioma, IDH-mutant, and 1p/19q codeleted**

deficits [57, 58].

Surgical treatment with the goal of early radical surgery is nowadays the first step in the standard of care of low-grade gliomas. Complete tumor removal based on functional borders more than on imagistic ones with the help of neuronavigation, awake surgery, and intraoperative neurophysiological monitoring (IEM) proved to offer a longer progression-free survival (PFS) and overall survival (OS) compared with subtotal removal, with reduced neurological

Knowing that the wild-type astrocytomas have a worse prognosis, a low-dose radiotherapy regimen in the immediate postoperative period is recommended instead of close clinical imagistic observation. There are arguments in favor of radiotherapy in terms of prolonged PFS but not necessarily the OS [59]. Due to the fact that the patients receiving associated radiotherapy and chemotherapy have an improved long-term survival [60], a combined radio-chemotherapy regimen seems to be recommendable. Further studies will have to determine whether temozolomide, which was historically preferred by neuro-oncologists due to its lower toxicity

**Definition**. A diffuse astrocytoma for which the presence of the IDH mutation could not be

**Definition**. Tumor with a diffuse growth pattern, slow growth, showing IDH mutations and the 1p/19q codeletion. Oligodendrogliomas develop many similarities with DA IDH-mut con-

**Clinical presentation**. The classical presentation of a patient with oligodendroglioma is with seizures that precede with years and with other neurological signs like mental disturbances, neurological deficits, or signs of increased intracranial pressure (mostly headache). Even in patients with no seizures at the onset, they will develop such clinical manifestations during the course of disease. The brutal debut due to an intratumoral hemorrhage although rare, is more frequent in oligodendrogliomas than in other low-grade

**Imaging**. *CT scan* is usually the first imagistic tool in emergency, and for more than 50% of oligodendrogliomas that present intratumoral calcification, it is a useful diagnostic method. On CT scan, oligodendrogliomas are present as well-delineated cortical-based hypodense lesion with intratumoral or peripheral calcification. Cystic component are not rare and hemorrhagic regions may also be encountered (**Figure 6**). Contrast enhancement is absent or marginal.

cerning clinical presentation, imagistic diagnosis, and therapeutical management.

**Figure 6.** Axial and coronal CT scan examination of a case with an hypodense left frontal lobe lesion with intratumoral calcifications and discrete enhancement (a and b).

**Figure 7.** Axial T2W (a), axial (b) and coronal (c) FLAIR sequences of a left frontal oligodendroglioma.

Recently, it was suggested that presence of calcification is highly associated with 1p/19q codeletion and, as a consequence, has a prognosis role [63].

*Standard MRI* reveals an hyperintense inhomogeneous lesion on T2W and FLAIR sequences, respectively, an inhomogeneous hypointense cortical-based well-delineated lesion on T1W sequences with no or discrete enhancement. Calcifications, cysts, and hemorrhagic lesions increase the heterogeneity of the lesion (**Figure 7**).

**Advanced MRI techniques**. As for the diffuse astrocytomas, MRI spectroscopy reveals higher NAA (N-acetylaspartate) peak near 2 ppm. The mIns (myoinositol) peak is relatively higher when compared with normal brain; the reduction of peak signaling is a possible malignant transformation of tumor. The NAA/Cr (creatinine) ratio is higher in low-grade gliomas, meanwhile the ratio Cho(Choline)/Cr is higher in high-grade gliomas [64]. As it was already mentioned, 2HG peaks serve as an indicator for IMD 1 mutation. Perfusion MRI, an another physiologic imaging sequence, reveals that relative cerebral blood volume (rCBV) is reduced in low-grade gliomas (LGG) compared with high-grade ones. Increase in rCBV in a LGG is an indicator for rapid progression and possible malignant transformation (**Figure 8**) [65]. Diffusion tensor imaging (DTI) could also add some supplementary information in order to differentiate LGG from high-grade gliomas (HGG) [66].

**Figure 8.** T1W + C sequence (a), DTI (b) and perfusion MR (c) sequences in a patient with a LGG with a nodule of contrast enhancement corresponding to a region of increased rCBV; the patient presented 4 years previously for epileptic fits; MRI examination performed at that time was suggestive for a LGG, but the patient refused any treatment except the antiepileptic one; readmitted for signs of increased intracranial pressure and clear imagistic findings for progression and malignant transformation.

**Macroscopy**. It is a well-defined lesion at the interface between the white and the gray matter (*with an affinity for the cerebral cortex*). In cross-section, the surface is soft and frequent calcifications gives it a gritty look. Hemorrhagic and cystic degeneration areas can be seen.

**Histological diagnosis**. The aspect is that of an infiltrative tumor consisting of monomorphic cells. Cellularity is moderately increased, but it can vary considerably. The well-differentiated tumors can feature well-circumscribed nodules of increased cellularity. The nuclei are slightly enlarged, uniform, round (low atypia), and slightly hyperchromatic ("salt and pepper"). In hematoxylin-eosin, they are surrounded by a water clear cytoplasm with sharp borders, which gives them the artefactual aspect of fried egg or honeycomb. Typically, they show a network of branching capillaries in a chicken wire shape. Calcifications, cysts, and areas of mucoid degeneration can also be encountered. Mitoses are rare [67]. Immunohistochemically, the cells are IDH+ and ATRX+, and p53− [3]. GFAP and vimentin are variably expressed. Olig1 and Sox10 are positive but non-specific [68]. The differential diagnosis can be done with macrophage-rich lesions, diffuse astrocytoma, and clear cell ependymoma.

The use of neuronavigation with co-registered preoperative T2W and FLAIR sequences and CT scan data in the presence of intratumoral calcification improved the grade of resection (**Figure 10**). As for other LGG, intraoperative electrostimulation mapping (IEM) on awake patient greatly improved not only functional outcome of the patient but also made possible to extend safely the grade of resection, with a great impact on the prolonged survival rate [72].

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**Figure 10.** Preoperative T2W and T1W + C (a and b), respectively; 12 months postoperative T2W and T1W + C (c and d) sequences of a case with left frontal oligodendroglioma completely removed without any neurological deficit; (e) intraoperative aspect after completion of radical removal of a right temporal low-grade glioma with the preservation of

**Figure 9.** Molecular sand histopathological diagnosis of oligodendrogliomas.

Labbe vein (personal archive).

**Genetic diagnosis**. By definition, these tumors feature mutations in the IDH1 and IDH2 genes, as well as the deletion of the whole arm of the 1p and 19q chromosomes [69]. The incomplete/partial codeletion is present in glioblastomas and anaplastic astrocytomas. TERT mutation is associated with the IDH mutation and codeletion in the early onset of the tumor. *CIC* and *FUB* occur at a later stage [70]. The TP53 mutation is absent. As to the epigenetics, just like in the other cases, the IDH mutation induces a hypermethylated status—G-CIMP [38]. The methylation of the MGMT promoter is associated with a better survival rate, given the response to treatment (**Figure 9**) [71].

### *2.4.1. Multimodal treatment*
