**3. High-grade gliomas**

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

**Definition**. Tumoral proliferation which, from a histopathological point of view, displays an astrocytic phenotype, a diffuse growth pattern and proliferative activity, and which, genetically speaking, features mutations in the IDH1 or IDH2 genes.

**Figure 13.** Upper row: left frontal lesion hyperintense in T2W (a) and FLAIR (b) sequences with no contrast and T1W sequence (c) MRI in a 24 years old men diagnosed with grade III astrocytoma; lower row: left frontal lesion having similar characteristics in T2W (d) and FLAIR (e) sequences but with a discrete enhancement in T1W (f) sequences revealed in the young men's father MRI examinations, operated 5 years before with an anaplastic astrocytoma (personal archive) suggesting a hereditary determinism in this particular case.

the presence of several mitoses is not sufficient for a diagnosis. The nuclei are larger, hyperchromatic, and their shapes vary more than in the case of grade II astrocytomas, while the nucleoli are more visible. Multinucleated cells, gemistocytes, small cells, and perivascular lymphocytes can

**Figure 14.** The immunohistochemical analysis (Clone H09) of the IDH1 R132H mutation performed on a patient with anaplastic astrocytoma. Infiltrating tumor cells positives at cytoplasmic level are observed in a background of negative normal astrocytes (left). In vivo single-voxel localized PRESS spectra were performed for the same patient. Black line represents the sum of spectra obtained during MRS. Pink line represent the spectra of 2-hydroxyglutarate identified at

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*The immunohistochemical profile* is the same as in the grade II IDH-mutant diffuse astrocytoma: Olig2+, IDH1 R132H+, ATRX−, and p53+ in some cases. The Ki-67 proliferation index is generally high (5–10%), but it can vary considerably [77]. The differential diagnosis is performed with reactive gliosis, demyelinating diseases, progressive multifocal leukoencephalopathy,

**Genetic diagnosis**. Generally, it matches that of grade II astrocytomas. The IDH 1/2 mutation is present by default, in association with TP53 and ATRX. Chromosome arm 9p and 19q losses are more frequent in grade III tumors. As with grade II astrocytomas, the presence of the IDH mutation means a better prognosis, with the median survival rate for these patients being 9.3 years. The presence of EGFR, 10q loss, and 7q gain means a less favorable prognosis, and may suggest a molecular diagnosis of glioblastoma, even if there is no indication of it in the

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

**Genetic diagnosis**. One in five anaplastic astrocytomas does not feature the IDH mutation, the genetic profile and the clinical evolution of these tumors being that of wild-type glioblastoma.

plasia, and which, genetically speaking, does not feature mutations in the IDH gene.

also be seen. There are no calcifications, necrosis, or microvascular proliferation [76].

grade II astrocytoma, glioblastoma, and anaplastic oligodendroglioma.

histology (**Figure 14**) [35]. By definition, the 1p/19q codeletion is absent.

**3.2. Anaplastic astrocytoma, IDH wild-type**

**Grading**. Grade III tumor.

TE 35 ms (right).

**Grading**. Diffuse astrocytoma is deemed grade III WHO.

*Clinically*, the patients experience seizures, headache, neurocognitive disturbances, and neurological deficits in more advanced stages.

**Imaging**. MRI features are quite variable, with isointense mixed with hypointense signaling on T2 W sequences and heterogeneous hyperintensity in T2W and FLAIR sequences. The contrast enhancement is subtle or is lacking in majority of cases [75] (**Figures 13** and **14**).

**Macroscopy**. Anaplastic astrocytoma appears as an expansion of the tissue tending to infiltrate the surrounding nervous structures, but without destroying them. It is difficult to distinguish from the grade II astrocytoma, but the increased cellularity makes it easier to identify the edges of the tumor. Also, in cross section, we see areas of low consistency, granular, or opaque. Cysts are rarely encountered.

**Histological diagnosis**. The aspect is that of a tumoral proliferation with astrocytic phenotype and a diffuse growth pattern. As compared to grade II astrocytomas, it shows increased cellularity, anaplasia, and mitotic activity. These three parameters can vary between grade II astrocytoma and glioblastoma and must therefore be assessed in context. A heightened mitotic activity is sufficient for a diagnosis, even if the cellularity is low or normal. Also, just one mitosis in a stereotactic biopsy can be sufficient for a diagnosis. There are also atypical mitoses. In a large biopsy, Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management http://dx.doi.org/10.5772/intechopen.76205 111

**Figure 14.** The immunohistochemical analysis (Clone H09) of the IDH1 R132H mutation performed on a patient with anaplastic astrocytoma. Infiltrating tumor cells positives at cytoplasmic level are observed in a background of negative normal astrocytes (left). In vivo single-voxel localized PRESS spectra were performed for the same patient. Black line represents the sum of spectra obtained during MRS. Pink line represent the spectra of 2-hydroxyglutarate identified at TE 35 ms (right).

the presence of several mitoses is not sufficient for a diagnosis. The nuclei are larger, hyperchromatic, and their shapes vary more than in the case of grade II astrocytomas, while the nucleoli are more visible. Multinucleated cells, gemistocytes, small cells, and perivascular lymphocytes can also be seen. There are no calcifications, necrosis, or microvascular proliferation [76].

*The immunohistochemical profile* is the same as in the grade II IDH-mutant diffuse astrocytoma: Olig2+, IDH1 R132H+, ATRX−, and p53+ in some cases. The Ki-67 proliferation index is generally high (5–10%), but it can vary considerably [77]. The differential diagnosis is performed with reactive gliosis, demyelinating diseases, progressive multifocal leukoencephalopathy, grade II astrocytoma, glioblastoma, and anaplastic oligodendroglioma.

**Genetic diagnosis**. Generally, it matches that of grade II astrocytomas. The IDH 1/2 mutation is present by default, in association with TP53 and ATRX. Chromosome arm 9p and 19q losses are more frequent in grade III tumors. As with grade II astrocytomas, the presence of the IDH mutation means a better prognosis, with the median survival rate for these patients being 9.3 years. The presence of EGFR, 10q loss, and 7q gain means a less favorable prognosis, and may suggest a molecular diagnosis of glioblastoma, even if there is no indication of it in the histology (**Figure 14**) [35]. By definition, the 1p/19q codeletion is absent.
