Neuro-oncology

Primary brain tumors can occur at any age, from infancy to late in life. These tumors often afflict people during their prime years. Factors such as age, tumor location, and clinical presentation are helpful in differential diagnosis. Most types of primary brain tumors are more common in men with the exception of meningiomas, which are more common in women.[2]

Human Central Nervous System

Cancer spreads to the nervous system by direct invasion, compression, or metastasis. Direct invasion or compression from continuous tissues relates to the proximity of the nervous system to other structures, such as the brachial plexus, lumbosacral plexus, vertebral neuroforamina, base of skull, cranium, and pelvic bones.[2]

There are three types of intracranial metastasis: brain metastasis, dural metastasis, and leptomeningeal metastasis. Brain metastasis can be single or multiple and involve any portion of the brain. Metastasis to dural structures generally occurs by hematogenous spread or direct invasion from a contiguous bone. Dural metastases can invade the underlying brain and cause focal edema and associated neurologic symptoms. These processes tend to cause seizures early in the course because of their cortical location. Metastasis to the leptomeninges is an uncommon but well-recognized clinical presentation in cancer patients. Leptomeningeal metastasis most commonly is due to breast, lung, or melanoma primary tumors.[2]

Metastases to the skull are divided into two categories by general site: calvarium and skull base. Metastases to the calvarium usually are asymptomatic. Metastases to the skull base quickly become symptomatic because of their proximity to cranial nerves and vascular structures.[2]

The spine most often is affected by metastatic disease involving the epidural space. This usually occurs as direct tumor spread from a vertebral body (85%) or by invasion of paravertebral masses through a neuroforamin (10–15%).[2]

There are multiple hereditary conditions that increase a person's chance of developing brain tumors.

Few issues in medicine are as potentially contentious as the suspicion of environmental and occupational causes of cancer, including brain tumors. Prior cranial irradiation is the only risk factor that definitely predisposes to brain tumor formation. Some of the risk factors are ionizing radiation, nonionizing radiation, nitrosamines and industrial chemicals.

Seizures are common in patients with low-grade tumors such as dysembryoblastic neuroepithelial tumors, gangligliomas, and oligodendrogliomas. The rapid growth of fast-growing high-grade brain tumors may damage the subcortical network essential for electrical transmission, whereas slow-growing tumors have been suggested to induce partial deafferentation of cortical regions, causing denervation hypersensitivity and producing an epileptogenic milieu. Studies strongly suggest that genetic factors may play a role in tumor development and tumor-related epilepsy.[3][4]

The location of tumors is closely related to their histology. The majority of glioneuronal tumors occur in the temporal lobe. Some data have shown that oligodendroglial tumors were more likely to be located in frontal lobe, whereas astrocytomas were more commonly found in temporal locations. It may be postulated that tumor-related seizures have unique characteristics, which may share some common genetic pathways with tumorigenesis.

Human and animal studies have suggested that perturbations in neurovascular integrity and breakdown of the BBB lead to neuronal hypersynchronization and epileptiform activity. Relevant molecular changes in brain tumors that affect BBB structure and function include decreased expression of transmembrane junctional proteins and heightened release of vascular endothelial growth factor. Results suggest that pathological disruption of the BBB in brain tumor patients may contribute to seizure activity.

Contemporary imaging techniques provide testimony to the remarkable differences between the peri-tumoral brain and normal tissue.

Certain morphological changes in the peri-tumoral brain tissue, such as persistent neurons in the white matter, inefficient neuronal migration, and changes in synaptic vesicles, are also believed to contribute to seizure generation.

Tumors with insufficient blood supply often cause interstitial hypoxia, which subsequently contributes to acidosis. The intratumoral hypoxia and acidosis may extend to the surrounding tissue. Furthermore, hypoxia causes acidosis as a consequence of both heightened metabolic requirements of the proliferating tissue and impaired oxidative energy metabolism.

Ionic changes in the peri-tumoral zone may influence neuronal activity. An interesting hypothesis was proposed by Sontheimer, who suggested that glioma invasion into the peri-tumoral zone is in part mediated by chloride channel overexpression, allowing cells to traverse the extracellular space through rapid changes in cell shape.

Recent work has demonstrated a close link between seizure activity and high extracellular glutamate in tumor-related epilepsy. Glutamate activation of ionotropic receptors leads to a rapid excitatory signal based on cation influx that can cause release of calcium from intracellular stores.[2]

The imaging studies commonly used in neurooncology are computed tomography (CT) and magnetic resonance imaging (MRI). Less commonly used are myelography, positron emission tomography (PET), and diagnostic angiography.[7][8]

Lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis are important for the evaluation of some primary tumors, metastatic conditions, and neurologic complications of cancer.[7]

Accurate histologic diagnosis is critical for treatment planning and patient counseling. Surgically obtained tissue usually is required to make a histologic diagnosis. For certain tumors, a definitive diagnosis can be accomplished by vitreous aspirate, cerebrospinal fluid (CSF) cytology, or suggested by the presence of certain tumor markers in the CSF.[7]

1. Malignant Astrocytomas

Malignant astrocytomas are the most common primary brain tumors in adults. Malignant astrocytomas generate symptoms and signs by mass effect, local brain infiltration, tissue destruction, cerebral edema, and increased intracranial pressure. Headaches and seizures are the most frequent initial symptoms. Associated focal neurologic signs and symptoms occur depending on the anatomic location of the tumor. Confusion and mental status difficulties occur in patients with large tumors, those that cross the corpus callosum and those with a lot of associated edema.[10]

2. Other Astrocytomas

Tumors of presumed or known astrocytic lineage other than the malignant astrocytomas include a variety of tumors categorized by histology, location, age of onset, and natural history.[10]

3. Oligodendrogliomas

The oligodendrogliomas include low-grade oligodendroglioma, anaplastic oligodendroglioma, and oligoastrocytoma (mixed glioma). This group of tumors, although less common than astrocytomas, has received increased attention in the past decade because of reports of chemosensitivity and a favorable survival rate when compared with astrocytomas of similar grade.[10]

4. Brain Stem Gliomas

Brain stem glioma is a distinct category of central nervous system tumor because of its unique location and behavior. The histology of brain stem gliomas spans the spectrum of gliomas located elsewhere in the central nervous system. The cause of these tumors is still unknown. Researchers have not found any direct genetic link.[10]

5. Pituitary Region Tumors

A wide variety of tumors can occur in and around the sella turcica. The most common tumors in this region are craniopharyngiomas, pituitary adenomas, meningiomas, and optic chiasm gliomas. Visual impairment is a common presenting symptom, due to compression or invasion of the optic chiasm.[10]

6. Germ Cell and Pineal Region Tumors

Most tumors of the pineal region are either germinomas or pineal cell tumors, and are tumors of adolescents and young adults. Presentation relates to the location in the nervous system.[11]

7. Medulloblastoma and Other Primitive Neuroectodermal Tumors

Medulloblastoma and other primitive neuroectodermal tumors (PNETs) are a group of highly aggressive central nervous system tumors with a tendency to spread via cerebrospinal fluid pathways. These typically are tumors of childhood and young adulthood.[11]

8. Meningiomas and Other Meningeal Tumors

Meningioma is the most common tumor in the central nervous system. Although most are slow growing and histologically benign, they can induce significant symptoms depending on location.[11]

9. Tumors of the optic nerve and optic chiasma

These tumors include the tumors involving the orbit and optic pathways, which include optic nerve gliomas and optic nerve sheath meningiomas.[12]

10. Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL), a rare central nervous system tumor, occurs preferentially in immunocompromised patients; however, it is increasing in incidence in both the HIV and non-HIV populations.[12]

11. Primary Spinal Cord Tumors

Primary spinal cord tumors are uncommon and most are either astrocytomas or ependymomas.[12]

1. Spinal Cord Metastasis

The management of spinal cord metastasis depends on whether or not the metastasis is causing epidural spinal cord compression as well as the overall status of the patient's systemic cancer.[13]

2. Brain Metastasis

The occurrence of brain metastases represents a significant challenge in the care of patients with cancer. Symptoms may significantly alter the quality of life of affected patients, and brain metastases generally represent overall treatment failure. Long-term survival is poor.[13]

3. Leptomeningeal Metastasis

Leptomeningeal metastasis (LM) is a rare complication of systemic cancer in which the leptomeninges are infiltrated by cancer cells. The overall incidence is 3–8% but is increasing as more cancer patients survive following initial treatment.[13]