1. Astrocytomas
Stud. Francesca Ochea, Carol Davila University of Medicine and Pharmacy
Coord. assoc. prof. dr. Ligia Tataranu, Bagdasar-Arseni Emergency Hospital

2. Gliomas
Gliomas comprise a group of primary central nervous system (CNS) neoplasms with characteristics of neuroglial cells (eg, astrocytes, oligodendrocytes) that express varying degrees of aggressiveness.
The slower growing lesions are commonly referred to as low-grade gliomas (LGGs), while the more rapidly progressive tumors are referred to as high-grade gliomas (HGGs).
LGGs are less common, comprising approximately one-fifth of CNS glial tumors.

3. Brain tissue infiltration
WHO grading system
Grade
Brain tissue infiltration I
Small zone of infiltration
Eg. Pilocytic astocitoma II
Diffuse infiltration, low malignity
Eg. Diffuse astroytoma
III
Diffuse infiltration, high malignity
Eg. Anaplastic astrocytoma IV
Diffuse infiltration, extreme malignity
Eg. Glioblastoma

4. Low Grade Gliomas
LGGs can be divided into several distinct entities based upon their histopathologic appearance.
These differences correlate with important differences in biologic behavior and thus have important implications for patient management.
LGGs can develop anywhere in the CNS, although studies usually are directed to a particular location (eg, cerebral hemispheres, optic pathways, brainstem).

5. Low Grade Gliomas
Bailey and Cushing originally proposed that gliomas were derived from transformation of normal glial cells during their development.
Astrocytomas were tumors with the appearance of astrocytes, while oligodendrogliomas had the appearance of oligodendrocytes.
Kernohan estimated the prognosis of glial tumors based upon the extent of observed anaplastic features (ie, mitoses, endothelial proliferation, cellular atypia, necrosis).
Such a classification proved to be of prognostic value, especially for astrocytomas.

6. Low Grade Gliomas
Although the term LGG is widely used, it is not explicitly defined in either system.
LGG describes a spectrum of primary brain tumors composed of cells that histologically resemble one or more differentiated types of macroglial cells (diffuse and fibrillary astrocytes, oligodendrocytes, ependymal cells) without evidence of anaplasia.
In the Kernohan scheme, LGGs encompass grade I and II tumors.

7. Low Grade Gliomas

8. Low Grade Gliomas
LGGs have been referred to as "benign" gliomas, but this is a misnomer.
Although these tumors have a more favorable natural history than HGGs, LGGs are only occasionally associated with prolonged (>10 years) survival and frequently develop characteristics similar to more aggressive brain tumors.

9. Low Grade Gliomas
A tentative diagnosis of LGG often can be made based upon the clinical presentation and imaging findings.
An LGG is highly likely when a patient presents with a transient neurologic disturbance consistent with seizure and imaging studies (MRI and/or CT) reveal a nonenhancing hemispheric lesion that produces little mass effect .
By MRI, these tumors are best seen on T2-weighted MRI sequences.
They are frequently nonenhancing on T1-gadolinium sequences.
Calcifications are sometimes present, most commonly in oligodendrogliomas.

10. Low Grade Gliomas
There is an abnormal poorly enhancing well defined intra-axial lesion in the subcortical white matter of left high parietal lobe. The lesion is seen as hypointense on T1, hyperintense on T2 and FLAIR.
There is an abnormal poorly enhancing well defined intra-axial lesion in the subcortical white matter of left high parietal lobe.
The lesion is seen as hypointense on T1.

11. Low Grade Gliomas The lesion is seen as hyperintense on T2 and FLAIR.
No perilesional edema is noted. No evidence of necrosis, hemorrhage or calcification are seen in the lesion. Mild mass effect is seen in the form of effacement the underlying cortical sulci in the parafalcine area.
The lesion is seen as hyperintense on T2 and FLAIR.

12. Diffuse astrocytomas
Diffuse astrocytomas generally occur in adults with a peak age incidence in their late 30s, approximately 20 years younger than in those with HGGs.
Most commonly arise in the cerebral hemispheres.
Widely infiltrate surrounding neural tissues.

13. Diffuse astrocytomas
Can be subdivided based upon their histopathologic appearance into the following variants:
●Fibrillary — Fibrillary tumors typically arise from deeper white matter. They are firm and rubbery due to the neuroglial fibrils that they produce. Microscopically, fine neuroglial fibrils form a matrix between the cells.
●Gemistocytic — Gemistocytic astrocytomas are composed of gemistocytes, which are cells that appear exceptionally large and are densely packed. In many cases, distention of their cell bodies results in a globoid appearance . Although it has been suggested that these tumors are better classified as anaplastic astrocytomas, the reported survival figures and prognostic determinants generally mirror those for diffuse fibrillary astrocytomas .
●Protoplasmic — Astrocytoma cells can resemble protoplasmic astrocytes. Protoplasmic tumors are the least common variant of diffuse astrocytomas and tend to arise in the cerebral cortex. They may have a better prognosis than other diffuse astrocytomas.

14. Low grade gliomas
Although the natural history of low-grade gliomas vary greatly, most patients eventually deteriorate.
For many patients there will be a period of relative radiographic and clinical stability that averages five to seven years for astrocytic tumors and often longer for oligodendroglial tumors.
However, tumor growth eventually accelerates, and the clinical course then is indistinguishable from that of an high-grade glioma (ie, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, glioblastoma).

15. Low grade gliomas
Immediate surgery is generally required for patients presenting with a large mass or extensive neurologic symptoms, both to establish the diagnosis and debulk the tumor.
Gross total resection is often not possible without a significant risk of serious neurological sequelae because of the diffuse infiltrative nature of these tumors, however, and a combined modality approach using adjuvant radiation therapy and/or chemotherapy may be indicated.
The optimal timing of additional therapy is uncertain, however, and the decision to proceed with immediate versus delayed postoperative therapy must be individualized.

16. Low grade gliomas
●For young patients (≤40 years) who undergo complete resection of a tumor with favorable molecular features, is recommended initial observation after surgery. It is expected that these patients will eventually recur and require additional therapy at the time of progression.
●For older patients with residual disease and one or more unfavorable molecular features, is suggested immediate postoperative therapy.
●For patients who do not fall into either of these categories, the more risk factors present, the more likely the patients are to be treated with immediate postoperative therapy.

17. High grade gliomas
High-grade gliomas are malignant, often rapidly progressive brain tumors that are divided into:
anaplastic gliomas (anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma)
glioblastoma (GBM)
based upon their histopathologic features.

18. High grade gliomas
Patients with high-grade glioma typically present with subacute and progressive neurologic signs and symptoms that vary according to the location of the tumor within the brain.
Magnetic resonance imaging (MRI) of the brain provides confirmatory evidence of a mass lesion, but a tissue diagnosis is ultimately required to distinguish high-grade gliomas from other primary and metastatic brain tumors.

19. High grade gliomas
Contrast-enhanced MRI is superior to computed tomography (CT) for the characterization of brain tumors. On MRI, high-grade gliomas are typically hypointense on T1-weighted images, and enhance heterogeneously following contrast infusion.
Enhancing tumor can be distinguished from the surrounding hypointense signal of edema on T1-weighted sequences.
Regardless of the histologic grade, high-grade gliomas generally show increased T2 and FLAIR signal intensity. However, some anaplastic gliomas do not manifest contrast enhancement.

20. High grade gliomas
MRI of the brain demonstrates a large heterogeneously enhancing tumour in the left parietal lobe extending down towards the ventricle. It has a non-enhancing central fluid signal component suggesting central necrosis. There is surrounding oedema with mass effect. 

21. High grade gliomas

22. High grade gliomas
Typical appearances of a butterfly glioma, with little possible differential. 
Pathologically proven.

23. High grade gliomas
A tissue diagnosis in patients with a presumed high-grade glioma is essential.
This can be accomplished either at the time of surgical resection or in a separate biopsy procedure.
Biopsy alone is used in situations where the lesion is not amenable to resection, a meaningful amount of tumor tissue cannot be removed, or the patient's overall clinical condition will not permit surgery.
In the remaining cases, maximal safe resection is the preferred initial approach to both diagnosis and management

24. High grade gliomas
The initial treatment for high-grade gliomas is resection. Maximal resection with preservation of neurologic function is an important goal in the initial management of patients with high-grade gliomas, and the extent of surgery must be balanced with preservation of neurologic function.
The available evidence suggests that aggressive resection is associated with improved functional status and possibly with prolonged survival.

25. High grade gliomas
The most important prognostic factors affecting outcome in patients with high-grade glioma are age, tumor grade (anaplastic glioma versus GBM), Karnofsky performance status (KPS) and several molecular genetic alterations.
The extent of initial surgical resection also appears to influence prognosis.

27. High grade gliomas
High-grade gliomas are rapidly progressive tumors that are best managed with a combined modality approach, incorporating maximal surgical resection, adjuvant postoperative radiation therapy, and adjuvant chemotherapy.

28. Take home messages
Low grade gliomas are slower growing lesions than high grade gliomas.
Low grade gliomas are not benign tumors. LGG’s will eventually reccur and develop characteristics similar to HGG’s.
Immediate surgery with gross total resection is recommended for both types, while adjuvant therapy must be individualised based on patient’s comorbidities and HP findings.
The best treatment is total resection without neurological damage.

29. Thank you!