2.2 Benign Tumors and Malignant Tumors
Benign Tumors
The cells of a benign tumor reproduce very slowly; their mass is well delimited from the surrounding tissue and they do not diffuse to other locations. Meningiomas, neurinomas, pituitary adenomas, craniopharyngiomas are typical intracranial benign tumors, although with occasional exceptions. A benign intracranial tumor may be clinically malignant, if its location is particularly delicate and the operation difficult for the neurosurgeon and unsafe for the patient. In these cases, surgery may be ineffective for a definitive cure.

Malignant Tumors
These tumors are made up of cells that grow and divide rapidly and have unclear boundaries from the surrounding tissue. The adjacent brain becomes rapidly suffering; the patient develops brain edema and the tumor cells appear monstrous, with angiogenesis and pleomorphism.
The malignant brain tumors diffuse in the CNS; they do not metastasize outside the CNS. Although generally not curative, neurosurgery is still the first and most effective therapeutic option also in malignant brain tumors.

The World Health Organization (WHO) suggested an international "grading" for brain tumors. This is an obvious simplification, but still the most widespread method for its simplicity and understandability, either for patients or for family doctors who are not accustomed to dealing with brain tumor patients.
This grading, which mainly applies to gliomas, is based on the following criteria:
Cellular atypia
Mitotic index
Uncontrolled cellular replication
Dead cells in the tumor tissue (necrosis)
Newly formed vessels (tumoral angiogenesis)
Surrounding tissue infiltration.

According to these criteria, brain tumors may be divided in:
WHO Grade I : these are benign tumors which can be cured with surgical removal, depending on their location. Pilocytic Astrocytoma and Ganglioglioma are examples of grade I tumors.
WHO Grade II : these are slow-growing tumors, whose cells are almost normal upon histological examination. Anyway, they may infiltrate the surrounding tissue and, over the years, they may become more aggressive. The rate of surgical removal of these tumors is directly related to prognosis. Fibrillary Astrocytoma and Oligodendroglioma are typical examples of this group.

- Grade I and II are grouped as the so-called low-grade gliomas.

WHO Grade III : these are tumors with intermediate aggressiveness. They recur, generally as more malignant. Neurosurgery, where possible, is the first and most effective therapy. Radiotherapy and chemotherapy follow and are decided on the basis of histological findings and other prognostic factors (see following paragraph). Anaplastic Astrocytoma and Anaplastic Oligodendroglioma are typical Grade III brain tumors.
WHO Grade IV : these are the most malignant. Glioblastoma Multiforme is an example of this group. Its cells are monstrous; its replication rate is high; there is major and diffuse angiogenesis, associated with areas of necrosis. Survival is limited. Glioblastomas recur and often diffuse to the whole brain, Gliomatosis. Anyway, when removed upon the first surgery and then treated by radio-chemotherapy, the median survival may reach 24 months.

- Grade III and IV are grouped as the so-called high-grade gliomas.


In the past few years, several biomolecular and genetic studies have been carried out on Gliomas and other tumors, in order to detect more reliable prognostic factors rather than the simple WHO classification. Actually, some genes have been identified in tumor cells, whose expression or depletion is associated with more favorable prognosis and/or with better response to radio-chemotherapy. This is not the discovery of the definitive glioma therapy, but an important research path to be followed in the coming years, as it seems to have direct clinical applications. Thus, neurosurgical centers should no longer classify their brain tumor patients only on the basis of the WHO grading system, but should identify all those genetic and growing rate data that are currently studied by the most advanced centers. As neurosurgical removal remains the most important step, these data are crucial to determining the type of therapy to be instituted and the rate of response to be expected in the individual cases. For instance, methylation of the MGMT gene promoter in glioblastoma cells is related to better response to radio-chemotherapy and then to better prognosis.

Primary brain tumors, i.e. those originating from structures that are in the skull, are rare. US epidemiologic data suggest 14 new cases/100,000/year.
The most frequent is Meningioma, which accounts for 27% of all intracranial tumors, followed by Glioblastoma Multiforme (GBM) (23%), Astrocytoma (12%), Neurinoma (8%), Pituitary Adenoma (7%), Lymphoma (3%), and Oligodendroglioma (3%).

In absolute terms, the most frequent intracranial tumors are Metastases from malignant tumors arising in other part of the body. Brain metastases are four times more frequent than primary brain tumors.