**3.3. Anaplastic astrocytoma NOS**

**Definition**. Diffuse anaplastic astrocytoma for which the presence of the mutation in the IDH gene could not be determined.

**Grading**. Grade III tumor.

## *3.3.1. Multimodal treatment*

### *3.3.1.1. Surgical treatment*

Being malignant tumors, early radical surgery represents the first step of the multimodal treatment of anaplastic astrocytomas. Due to the diffuse infiltration of the brain, radical excision is rarely achieved, meaning that if 1% of the initial volume remains in place, a local recurrence is almost certain. Additionally, the location of tumor in high eloquent areas prevents a radical excision in order not to produce severe neurological deficits. The main goals of surgery in highgrade gliomas (HGG) are to reduce the mass effect, to obtain relevant pathological tissue, to reduce the tumor burden, and to prolong survival with improved quality of life. There are many factors influencing OS in high-grade gliomas such as preoperative Karnofsky score, age, general and neurological status at the preoperative and postoperative period, pathology and genetics of the tumor, grade of resection, response and tolerance to the adjuvant therapy. Among all these factors only those related to surgery could be influenced, namely the grade of resection and the neurological status after the operation [78]. There is a very delicate balance between the radical surgery and preservation of neurological function. The more aggressive the surgery, the higher the risk for neurological deficiencies stands (**Figure 15**). After the publication of the trial conducted by Stupp and in 2005 [79], in which the role of surgery was minimized, a large amount of studies were published underlying the importance of gross total resection (GTR) compared not only with biopsy but also with near total resection (NTR) and subtotal resection (STS) as a factor that independently influences OS in HGG. For example, in anaplastic astrocytomas, there is a difference of 12 months in median of survival in favor of GTR compared with STR [80].

A retrospective study performed by us on 266 cases of HGG reveals the fact that gross total removal (GTR) greatly influences survival compared with STR. At the three periods of monitoring (12, 18, and 24 months), the difference regarding survival mean between GTR vs. STR ranged from 2.8 months (at 12 months monitoring) to 4.4 months (at 18 months monitoring) up to 5.1 months (at 24 months monitoring) including all types of malignant gliomas. We also found that the type of surgery and the age are prognostic factors that significantly influenced in all three periods of monitoring, while the histopathology was a prognostic factor for survival only at the 24 months monitoring (**Table 1**) [81].

**Grading**. The tumor is grade III WHO.

areas.

cits. Other signs are related to the location of tumor [82].

*Clinically*, the most frequent presenting symptom is seizures, less frequent than in the lowergrade tumors, accompanied with signs of increased intracranial pressure and cognitive defi-

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management

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

113

**Imaging**. On *MRI* studies, they are typically heterogeneous, predominantly hypointense in T1W, and respectively hyperintense in T2W sequences. The frontal lobe cortical based location, the presence of calcification, cystic degeneration and hemorrhage, and intense enhancement along with minimal perilesional edema are more suggestive for anaplastic oligodendroglioma than for other gliomas. For follow-up imagistic studies, the T2W and FLAIR sequences are more sensitive in identification the local progression [83]. *CT scans* usually performed in

**Macroscopy**. As compared to grade II oligodendroglial tumors, they show additional necrotic

**Microscopic diagnosis**. Increased cellularity, in a pattern that is infiltrative or compact with little intervening parenchyma. The cells have the characteristic fried egg aspect, but a significant pleomorphism or giant multinucleated cells can also occur. Significant mitotic activity is

emergency may clearly define calcification and hemorrhagic changes (**Figure 16**).

**Figure 15.** Integrated histological and molecular diagnosis of anaplastic astrocytoma IDH-mutant.

A more detailed discussion regarding the role of surgery will be presented later in the chapter, along with the types of glioblastomas.

### **3.4. Anaplastic oligodendroglioma, IDH-mutant, 1p/19q-codeleted**

**Definition**. Infiltrative tumor with the histopathological aspect of oligodendroglioma showing a significant proliferative activity and microvascular proliferations.

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management http://dx.doi.org/10.5772/intechopen.76205 113


**Figure 15.** Integrated histological and molecular diagnosis of anaplastic astrocytoma IDH-mutant.

**Grading**. The tumor is grade III WHO.

**3.3. Anaplastic astrocytoma NOS**

112 Glioma - Contemporary Diagnostic and Therapeutic Approaches

gene could not be determined.

**Grading**. Grade III tumor.

*3.3.1. Multimodal treatment*

*3.3.1.1. Surgical treatment*

**Definition**. Diffuse anaplastic astrocytoma for which the presence of the mutation in the IDH

Being malignant tumors, early radical surgery represents the first step of the multimodal treatment of anaplastic astrocytomas. Due to the diffuse infiltration of the brain, radical excision is rarely achieved, meaning that if 1% of the initial volume remains in place, a local recurrence is almost certain. Additionally, the location of tumor in high eloquent areas prevents a radical excision in order not to produce severe neurological deficits. The main goals of surgery in highgrade gliomas (HGG) are to reduce the mass effect, to obtain relevant pathological tissue, to reduce the tumor burden, and to prolong survival with improved quality of life. There are many factors influencing OS in high-grade gliomas such as preoperative Karnofsky score, age, general and neurological status at the preoperative and postoperative period, pathology and genetics of the tumor, grade of resection, response and tolerance to the adjuvant therapy. Among all these factors only those related to surgery could be influenced, namely the grade of resection and the neurological status after the operation [78]. There is a very delicate balance between the radical surgery and preservation of neurological function. The more aggressive the surgery, the higher the risk for neurological deficiencies stands (**Figure 15**). After the publication of the trial conducted by Stupp and in 2005 [79], in which the role of surgery was minimized, a large amount of studies were published underlying the importance of gross total resection (GTR) compared not only with biopsy but also with near total resection (NTR) and subtotal resection (STS) as a factor that independently influences OS in HGG. For example, in anaplastic astrocytomas, there is a difference of 12 months in median of survival in favor of GTR compared with STR [80].

A retrospective study performed by us on 266 cases of HGG reveals the fact that gross total removal (GTR) greatly influences survival compared with STR. At the three periods of monitoring (12, 18, and 24 months), the difference regarding survival mean between GTR vs. STR ranged from 2.8 months (at 12 months monitoring) to 4.4 months (at 18 months monitoring) up to 5.1 months (at 24 months monitoring) including all types of malignant gliomas. We also found that the type of surgery and the age are prognostic factors that significantly influenced in all three periods of monitoring, while the histopathology was a prognostic factor for sur-

A more detailed discussion regarding the role of surgery will be presented later in the chap-

**Definition**. Infiltrative tumor with the histopathological aspect of oligodendroglioma show-

vival only at the 24 months monitoring (**Table 1**) [81].

**3.4. Anaplastic oligodendroglioma, IDH-mutant, 1p/19q-codeleted**

ing a significant proliferative activity and microvascular proliferations.

ter, along with the types of glioblastomas.

*Clinically*, the most frequent presenting symptom is seizures, less frequent than in the lowergrade tumors, accompanied with signs of increased intracranial pressure and cognitive deficits. Other signs are related to the location of tumor [82].

**Imaging**. On *MRI* studies, they are typically heterogeneous, predominantly hypointense in T1W, and respectively hyperintense in T2W sequences. The frontal lobe cortical based location, the presence of calcification, cystic degeneration and hemorrhage, and intense enhancement along with minimal perilesional edema are more suggestive for anaplastic oligodendroglioma than for other gliomas. For follow-up imagistic studies, the T2W and FLAIR sequences are more sensitive in identification the local progression [83]. *CT scans* usually performed in emergency may clearly define calcification and hemorrhagic changes (**Figure 16**).

**Macroscopy**. As compared to grade II oligodendroglial tumors, they show additional necrotic areas.

**Microscopic diagnosis**. Increased cellularity, in a pattern that is infiltrative or compact with little intervening parenchyma. The cells have the characteristic fried egg aspect, but a significant pleomorphism or giant multinucleated cells can also occur. Significant mitotic activity is


**Genetic diagnosis**. Apart from the IDH mutation and the codeletion of the whole arm of the 1p and 19q chromosomes, the concurrent polysomy of 1p and 19q is more frequently encountered in anaplastic oligodendrogliomas [86]. Other chromosomal aberrations can occur: gain of 7, 8q, and 15q, and losses of 4q, 18, and 22q. Just like in the case of low-grade tumors, TERT, CIC, and FUBP1 mutations are present. Epigenetically, the IDH mutation induces G-CIMP,

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management

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

115

**Definition**. The diagnosis concerns the anaplastic oligodendrogliomas whose genetic profile

The diagnosis of *oligoastrocytoma* has been discontinued following the latest WHO classification.

As for the other types of gliomas, the grade of surgical resection is an independent factor for PFS and OS. As a consequence, GTR is recommendable wherever is possible without neuro-

**Figure 17.** Axial (a) and coronal (b) contrasted CT scan demonstrating the presence of a voluminous expansive lesion with large cystic components and peripheral calcification with a reduced perilesional edema, aspect highly suggestive for an anaplastic oligodendroglioma; after GTR the axial T2W (c) and coronal FLAIR (d) sequences at 2 years follow-up

while in most cases MGMT is hypermethylated [87].

(IDH mutation and 1p/19q codeletion) cannot be determined.

**3.5. Anaplastic oligodendroglioma, NOS**

*3.5.1. Multimodal treatment*

logical damage (**Figure 17**).

do not indicate a local progression.

**Table 1.** Disease free interval regarding the age, type of surgery, and histopathology.

**Figure 16.** Preoperative T2W and T1W+ C (a and b) sequences of a case with left frontal anaplastic astrocytoma completely removed; follow-up MRI performed at 4 months postoperatively and after concomitant radio- and chemotherapy with temozolomide showed no signs of local recurrence (c and d).

also present [84]. Sarcomatoid areas can be seen. The minigemistocytes are more numerous than in the case of grade II oligodendrogliomas [85]. As a characteristic, the chicken wire aspect is accompanied by microvascular proliferation. As opposed to grade II oligodendrogliomas, they can involve palisading necrosis. Secondary structures can also be encountered. Immunohistochemically, the profile is that of grade II tumors, with a higher proliferation index evinced by way of Ki-67 (generally >5%). The differential diagnosis can be done using clear cell ependymoma, glioblastoma, and anaplastic astrocytoma.

**Genetic diagnosis**. Apart from the IDH mutation and the codeletion of the whole arm of the 1p and 19q chromosomes, the concurrent polysomy of 1p and 19q is more frequently encountered in anaplastic oligodendrogliomas [86]. Other chromosomal aberrations can occur: gain of 7, 8q, and 15q, and losses of 4q, 18, and 22q. Just like in the case of low-grade tumors, TERT, CIC, and FUBP1 mutations are present. Epigenetically, the IDH mutation induces G-CIMP, while in most cases MGMT is hypermethylated [87].
