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Brain Tumors (Brain Cancers)

  • General:
    • Brain tumors:
      • Originate from neural elements inside the brain
      • Stem from metastatic cancer to brain.
      • Most brain cancers are metastatic.
      • Many types of brain cancer: Most common:
        • Gliomas,
        • Pituitary adenomas,
        • Meningiomas, and
        • Acoustic neuromas.
      • Can be supratentorial (above the tentorium) or infratentorial (below the tentorium).
      • Invade other tissues in the brain that are healthy.
      • Cause an increased intracranial pressure (ICP): Brain shifting and herniation (which can be fatal).
      • Block perfusion to parts of the brain.
      • Most do not metastasize but, for those that do, the cerebrospinal fluid is the vehicle for metastases.
      • Signs and symptoms tend to happen slowly.
      • In case of bleeding into the tumor, the symptoms may be sudden.
      • Manifestations of a brain tumor include:
        • Altered mental status,
        • Headaches,
        • Nausea,
        • Vomiting,
        • Ataxia,
        • Gait disturbance,
        • Blurry vision,
        • For generalized seizures,
        • Visual deficits,
        • Speech abnormalities,
        • Focal motor or sensory abnormalities,
        • Headaches are often a late finding and is the worst. Headache is worse in the morning.
      • CT scan with contrast and MRI are the imaging techniques of choice
    • Epidemiology
      • In US About 80,000 brain and CNS tumors are diagnosed per year with about 23,000 of them being cancerous.
      • Incidence is about 7-19 cases out of 100,000 people.
      • Metastatic tumors are far more common.
      • Pituitary adenomas are exceedingly common but are usually benign in nature.
      • Globally, about 257,000 brain cancers are diagnosed each year.
      • Brain tumors are the second most common cancer in children (up to 25 percent of all cancers).
      • Cerebellar cancers are higher in children and cerebral tumors are higher in adults.
    • Gliomas
      • General
        • Begin in the glial cells of the brain or spinal cord.
        • The most common brain cancer (primary brain malignancy),
        • Thirty percent of all brain tumors.
        • Gliomas aren’t all the same but are identified by cell type that they originate from:
          • Ependymoma (from ependymal cells): can be benign or malignant,
          • Astrocytoma (from astrocytes),
          • Oligodendroglioma (from oligodendrocytes),
          • Brain stem glioma (originating in the brain stem),
          • Optic nerve gliomas (around the optic nerve),
          • Mixed gliomas (from different glial cell types),
        • Glioblastoma multiforme is the most common brain tumor in adults and is the deadliest of all brain tumors,
        • Medulloblastomas are the most common type of childhood brain cancer: occur before age 10 years
        • Gliomas are classified by their grade (according to WHO guidelines).
          • Low-grade gliomas (WHO grade II) are not anaplastic and exhibit tendencies that make them slow-grow.
          • High-grade cancers (WHO Grade III-IV) are anaplastic, grow fast, and have a worsened prognosis.
        • Gliomas are also classified by their location: (The tentorium separates the cerebellum and cerebrum)
          • Above the tentorium (Supratentorial): adults about 70 percent or
          • below the tentorium (Infratentorial): 70 percent in children.
          • Pontine tumors are in the brainstem: Severe and affect the person’s vital functions (like heartrate and breathing).
        • Signs and symptoms
          • depend on the rate of growth, and
          • Location
          • Common symptoms:
            • Seizures,
            • Headaches,
            • Vomiting,
            • Vision loss,
            • Cranial nerve defects,
            • Weakness and numbness.
          • Metastases through the CSF (and not the blood or lymph system) so they can metastasize anywhere the CSF is located.
        • Etiology
          • Unknown
          • Hereditary disorders predispose getting a glioma:
            • Neurofibromatosis type 1,
            • Neurofibromatosis type 2, and
            • Tuberous sclerosis.
            • Infection with CMV is often found in glioblastomas and CMV-infected cancers spread faster.
            • Mutations in DNA repair genes will increase the risk of glioma: MGMT promotor repair gene, the ERCC1 repair gene, or in the isocitrate dehydrogenase (IDH) 1 or 2 genes.
          • Pituitary Adenoma
            • General
              • Occur in the pituitary gland.
              • Three different types:
                • Benign adenomas: 65% of pituitary adenoma, 10-25% of brain tumors,
                • Invasive adenomas: 35% of pituitary adenomas, and
                • Carcinomas: 0.1-0.2%
              • OR
                • Micro:
                  • Less than 10 mm in diameter.
                  • Most found incidentally on CT or MRI scan. No symptomatology.
                  • About 1 out of 1000 people need surgical intervention for their adenomas.
                • Macroadenoma: More than 10 mm in diameter.
              • OR
                • Functioning:
                  • Most common: Secretes both growth hormone and prolactin (causing unexpected bone growth and lactation)
                • Non-functioning:
                  • Undetected: Do not have hormonal complications until they grow and jeopardize pituitary function:
                    • Lack of GH, ACTH, prolactin, and TSH
                  • Pituitary adenomas are a part of MEN1 (multiple endocrine neoplasia type 1):
                    • Rare genetic disorder affecting only one out of 30,000 people.
                    • Affects the parathyroid glands and the pancreatic islet cells.
                    • Non-endocrine-related tumors can also result from this syndrome, such as ependymomas, meningiomas, lipomas, collagenomas, leiomyomas, and angiofibromas.
                  • Signs and Symptoms
                    • Visual field defects are common, particularly bitemporal hemianopsia from compression of the optic nerve at the optic chiasma. The actual visual field defect depends on the place where the tumor is growing in relation to the optic nerve.
                    • Prolactinomas start to become symptomatic in pregnancy because the hormone (progesterone) in pregnancy will increase the growth rate, sometimes leading to increased intracranial pressure.
                    • Headache, which can be like a migraine or cluster headache.
                    • Psychiatric symptoms of any type could sometimes be seen in pituitary adenoma cases.
                    • Acromegaly: Adenoma secreting excess growth hormone: Lead to gigantism and coarse facial features from bones.
                    • Cushing’s syndrome: Excess ACTH secretion.
                    • Hyperpituitarism: Adenoma secretes several hormones (like TSH, LH, FSH, ACTH, prolactin, and GH).
                    • Central diabetes insipidus can happen when the amount of vasopressin is diminished by an overgrown adenoma.
                    • Pituitary apoplexy happens with hemorrhage or tissue necrosis, leading to a sudden headache and loss of pituitary function.
                  • Meningiomas
                    • General
                      • Slowly-growing cancer
                      • Starts in the meninges.
                      • Symptoms due to pressure on brain tissue.
                      • Mostly asymptomatic.
                      • Gradual onset of:
                        • Dementia,
                        • Seizures,
                        • Visual problems,
                        • Hemiplegia, or
                        • Loss of bladder control.
                      • Age at 30 and 70 years of age.
                      • Symptomatic cases only need treatment
                      • Thirty percent of brain tumors.
                    • Risk factors
                      • Exposure to ionizing radiation.
                      • Positive family history of the disease.
                      • Neurofibromatosis 2.
                      • If surgically treated (needed): twenty percent recurrence after surgery.
                      • Chemotherapy does not help initially or with recurrences.
                      • Radiotherapy used to treat residual tumor.
                    • Etiology
                      • Radiation to the scalp: higher risk.
                      • Brain injury: higher risk.
                      • Neurofibromatosis 2: higher incidence.
                      • Eight percent: truly malignant.
                      • Genetically-mediated:
                        • Fifty percent of cases of meningioma have inactivity of their neurofibromatosis 2 gene on chromosome 22.
                          • Reasons aren’t clear.
                        • Twenty five percent will have a TRAF7 mutation.
                        • Less common mutations include KLF4, AKT1, and SMO gene mutations.
                      • Acoustic Neuroma
                        • General
                          • Slowly growing, mostly benign, and mostly non-invasive tumors of the vestibulocochlear nerve (CN VIII).
                            • They grow 1-2 mm each year, although half will stop growing for many years.
                            • Erratic periods of growth and no-growth
                            • Large acoustic neuroma is at least 2.5 cm in diameter: Giant acoustic neuromas: 4 cm in diameter.
                            • Large tumors will block the CSF flow in the brain.
                          • Could be called: Vestibular schwannoma.
                          • Neither acoustic nor a neuroma.
                          • Benign brain tumor of the myelin-forming cells of the 8th cranial nerve (the vestibulocochlear nerve).
                          • Arises from the Schwann cells that make the myelin-sheath.
                          • Usually arises from the vestibular portion of the nerve and not from the cochlear component.
                          • Can be inside the internal auditory canal, in the cistern (outside the canal), or in the cerebellum.
                          • About 2000-3000 new cases of acoustic neuroma are identified per year.
                          • Mostly diagnosed between the age of 30-60 years.
                          • Most with no family history.
                          • Major risk factor: the presence of the NF2 gene mutation.
                        • Signs and Symptoms
                          • Onset may be subtle.
                          • Fullness in the ears.
                          • Ninety four percent: Hearing loss
                            • Most common symptom in this disease.
                            • Unilateral with damage to the cochlear pathways to the brain or the cochlea itself.
                            • High frequencies are lost first.
                            • Gradually worsens with time.
                          • Tinnitus (83 percent),
                          • Vertigo (49 percent): Occurs with poor balance
                          • Large cancers: Present with trigeminal nerve or facial nerve injury (numbness or paralysis of the face on one side).
                          • Symptoms often persist, even with treatment.
                        • Etiology
                          • Tumor suppressor genes being defective or missing.
                            • Loss of a tumor repressor gene on chromosome 22 is most associated with the finding of acoustic neuroma.
                          • NF2 (neurofibromatosis 2) will lead to an acoustic neuroma because of deletion/mutation of chromosome 22.
                            • Incidence of acoustic neuroma is so high in NF2 cases: Most children or young adults will have this disease bilaterally (along with other brain or spinal cord tumors).
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