*2.4.1.1. Surgical treatment*

Surgical principles are the same with those of DA IDH-mut, gross total resection (>90% volume reduction on 24–48 h postoperative MRI) being correlated with a longer PFS and OS, compared with subtotal resection [57].

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

**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 calcifica-

**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

**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

**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].

Surgical principles are the same with those of DA IDH-mut, gross total resection (>90% volume reduction on 24–48 h postoperative MRI) being correlated with a longer PFS and OS,

tions gives it a gritty look. Hemorrhagic and cystic degeneration areas can be seen.

macrophage-rich lesions, diffuse astrocytoma, and clear cell ependymoma.

*2.4.1. Multimodal treatment*

malignant transformation.

106 Glioma - Contemporary Diagnostic and Therapeutic Approaches

*2.4.1.1. Surgical treatment*

compared with subtotal resection [57].

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].

**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 Labbe vein (personal archive).

**Figure 11.** Staged resection of a high-grade gliomas with the aid of intraoperative contrasted ultrasound: after the dural opening (a), partial resection (b) and after complete resection (c) of the tumor.

postoperative radiotherapy and those receiving radiotherapy as a salvage therapy, the actual recommendation is to delay radiotherapy until signs of progression are evident. In cases of incompletely removed tumors or in the presence of any imagistic or clinical signs of progression, combined radiotherapy and PCV chemotherapy is superior to radiotherapy alone (**Figure 12**) [73]. Some authors argued that even in cases with foci of anaplasia imbedded in low-grade glioma, the total resection is sufficient for a long-term PFS, and no adjuvant treatment is needed; but this is not the standard of care as the authors already mentioned at the conclusions [74].

transformation; re-operated in emergency, patient followed the standard radio-chemotherapy regimen.

**Figure 12.** Serial follow-up MRI examination of a patient with oligodendroglioma completely removed in September 2009, presenting with imagistic signs of progression 1 year later, but without any additional clinical manifestation; 15 months later the patient was readmitted for signs of increased intracranial pressure and clear findings of malignant

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management

http://dx.doi.org/10.5772/intechopen.76205

109

**Definition**. Infiltrative tumor with the histopathological aspect of oligodendroglioma, for which the genetic determinations relevant for the diagnosis (IDH mutation and 1p/19q code-

**Definition**. Tumoral proliferation which, from a histopathological point of view, displays an astrocytic phenotype, a diffuse growth pattern and proliferative activity, and which, geneti-

**2.5. Oligodendroglioma, NOS**

letion) cannot be determined.

**3. High-grade gliomas**

**3.1. Anaplastic astrocytoma, IDH-mutant**

cally speaking, features mutations in the IDH1 or IDH2 genes.

Despite the fact that there are no randomized trials comparing grade of resection with and without intraoperative MRI, it is intuitive that having real-time data on the progression of removal is at least useful for completion of tumor excision. An alternative is the intraoperative ultrasound which can detect significant remnants in real time without interruption of surgery (**Figure 11**). The introduction of new equipment with 4D and contrast enhancement dramatically improves the quality of images, but their role in detecting fine details in low-grade gliomas is to be established in near future.

### *2.4.1.2. Adjuvant treatment*

Immediate postoperative radiotherapy of completely removed oligodendroglioma IDH-mut 1p/19q codel is still under debate. Based on the results of EORTC 22845 trial which revealed that there is no significant difference in terms of OS between patients receiving immediate

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management http://dx.doi.org/10.5772/intechopen.76205 109

**Figure 12.** Serial follow-up MRI examination of a patient with oligodendroglioma completely removed in September 2009, presenting with imagistic signs of progression 1 year later, but without any additional clinical manifestation; 15 months later the patient was readmitted for signs of increased intracranial pressure and clear findings of malignant transformation; re-operated in emergency, patient followed the standard radio-chemotherapy regimen.

postoperative radiotherapy and those receiving radiotherapy as a salvage therapy, the actual recommendation is to delay radiotherapy until signs of progression are evident. In cases of incompletely removed tumors or in the presence of any imagistic or clinical signs of progression, combined radiotherapy and PCV chemotherapy is superior to radiotherapy alone (**Figure 12**) [73].

Some authors argued that even in cases with foci of anaplasia imbedded in low-grade glioma, the total resection is sufficient for a long-term PFS, and no adjuvant treatment is needed; but this is not the standard of care as the authors already mentioned at the conclusions [74].

### **2.5. Oligodendroglioma, NOS**

Despite the fact that there are no randomized trials comparing grade of resection with and without intraoperative MRI, it is intuitive that having real-time data on the progression of removal is at least useful for completion of tumor excision. An alternative is the intraoperative ultrasound which can detect significant remnants in real time without interruption of surgery (**Figure 11**). The introduction of new equipment with 4D and contrast enhancement dramatically improves the quality of images, but their role in detecting fine details in low-grade glio-

**Figure 11.** Staged resection of a high-grade gliomas with the aid of intraoperative contrasted ultrasound: after the dural

Immediate postoperative radiotherapy of completely removed oligodendroglioma IDH-mut 1p/19q codel is still under debate. Based on the results of EORTC 22845 trial which revealed that there is no significant difference in terms of OS between patients receiving immediate

mas is to be established in near future.

opening (a), partial resection (b) and after complete resection (c) of the tumor.

108 Glioma - Contemporary Diagnostic and Therapeutic Approaches

*2.4.1.2. Adjuvant treatment*

**Definition**. Infiltrative tumor with the histopathological aspect of oligodendroglioma, for which the genetic determinations relevant for the diagnosis (IDH mutation and 1p/19q codeletion) cannot be determined.
