Brain Tumors 5th year neuroscience M.Jamous M.D.

INCIDENCE: Second common cancer in children Accounts for 3.5% of all deaths in pediatric age group. 25% of all tumors in adults are in the brain.

Aetiology: Most primary tumors are sporadic and of unknown aetiology. Fewer than 5% are associated with hereditary syndromes that predispose to neoplasia.

Aetiology: 1. Sex – gliomas commoner in males meningiomas commoner in females Exposure to ionizing radiation implicated in the genesis of meningiomas gliomas nerve sheath tumors Primary CNS lymphoma – is associated with immunodeficiency

Occupational exposures multifactorial Being male Race Age Family history Occupational exposures  

Heritable syndromes with increased risk of CNS tumours Gene locus Gene Type of CNS tumour NF type 1 17q11 NF1 Neurofibro Mameningioma optic nerve glioma NF2 22q12 Meningioma, schwannoma Tuberous sclerosis 9q34,16p13 TSc1/TSC2 SEGA Vonhippel 3p35 VHL Haemangioblastoma Li-Fraumani 17q13 p53 glioma Gorlin’s syndrome 9q31 PNET

Presentation - Neurological deficit 68% - HA 54% - Seizures 26% (Depends on location, size, and type of tumor) - Neurological deficit 68% 45% motor weakness Mental status changes - HA 54% - Seizures 26%

Presentation - Increased intracranial pressure - Cerebral edema - Increased intracranial pressure - Focal neurologic deficits - Obstruction of flow of CSF - Pituitary dysfunction - Papilledema (if swelling around optic disc)

Clinical Presentation Insidious onset Headache Seizure Mental, behavioral and personality changes Lateralizing or focal neurologic deficits Increased ICP Slowly Progressive Tumors

Course of Illness

Ipsilateral limb ataxia Cerebellar tumor Hemisphere lesion Ipsilateral limb ataxia Intention tremor Dysmetria Vermis lesion Dysdiadochokinesia Truncal ataxia No limb ataxia

Site of brain tumors Adults Supratentorial: 80-85% Infratentorial: 15-20% - Children - Infratentorial: 60% - Supratentorial: 40%

Primary Secondary originates in the brain. made up of cells that have spread (metastasized) to the brain . Secondary Primary vs. secondary:

Localized Invasive spread to surrounding areas confined to one area easier to remove Invasive spread to surrounding areas more difficult to remove completely

Intraaxial Extraaxial Intraventricular mostly manifesting as seizures Meningioma Pituitary adenoma Vestibular schwanomma Intraaxial mostly manifesting as seizures Glioma Primary CNS Lymphoma Metastatic Intraventricular

Benign Malignant Cancerous slow-growing Fast-growing and aggressive Noncancerous do not spread to surrounding tissue. Malignant Cancerous Fast-growing and aggressive can invade nearby tissue and also are more likely to recur after treatment.

WHO Histologic Classification of Tumors of the CNS Tumors of Neuroepithelial Tissue Tumors of Cranial and Spinal Nerves Tumors of the Meninges Tumors of Uncertain Histogenesis Hemangioblastoma from primitive vascular structures Lymphomas and Hematopoietic Neoplasm Germ Cell Tumor Ex: Germinoma – common in pineal gland area Cysts and Tumor-like lesions Usually in the third ventricle Tumors of the Sellar Regions Local Extension from Regional Tumors Metastatic Tumors

Neurons

Glial Cells Schwann Cell Astrocyte Microglia Oligodendrocyte

- Neuroepitelial tumors : 1. Astrocytoma I, II benign III (anaplastic astrocytoma) - malignant IV (gliobastoma multiforme) 2. Oligodendroglial tumors Oligodendroglioma 3. Ependymal tumors Ependymoma

4. Mixed gliomas 5. Neuroepitelial tumors – unknown etiology 6. Chorioidal plexus tumors Papiloma papilocarcinoma 7. Neuronal and mixed neuronalglial tumors 8. Pineal parenchymal tumors 9. Tumors with neuroblastic or glioblastic elements (embryonal tumors) Meduloblastoma

- Tumors of sellar region 1. Pituitar adenoma 2. Pituitar carcinoma 3. craniopharyngioma - Hemopoetic tumors CNS lymphoma

- Tumors from germinative cells - Meningioma. - Tumors of cranial and spinal cord nerves Neurinoma (Schwannoma) Neurofibroma - Local tumors Chondrosarcoma Chondrocarcinoma - Metastatic tumors

Common types of brain tumors

GLIOMAS Most common primary brain tumor 50% of all symptomatic brain tumors Incidence increases with advancing age Ionizing radiation: the only clear risk factor Originate from glial cells or their stem cell precursors

GLIOMAS Include: Astrocytoma Oligodendroglioma Ependymoma

Astrocytoma Most common glioma Cerebral astrocytoma (more in adults) Cerebellar astrocytoma (more in children) Brain stem (children)

WHO GRADING SYSTEM for gliomas Benign Grade I-Pilocytic astrocytoma Moderate cellularity-no anaplasia or mitotic activity Grade II-Low-grade astrocytoma Cellularity, anaplasia, mitoses Grade III- Anaplastic astrocytoma Same as Grade III plus microvascular proliferation and necrosis Grade IV-Glioblastoma

WHO Classification: a. Increased cellularity b. Nuclear atypia c. Endothelial proliferation d. Necrosis

Grade I: Pilocytic Astrocytomas Primary in children & young adults Focal astrocytoma may be associated with: Neurofibromatosis type I (NF-I) excellent prognosis

Grade II: Diffuse or Fibrillary Astrocytoma Most common in the cerebral hemisphere in young adults Low grade or benign histologically Infiltrative – usually a problem because the tumor cannot be resected completely if this is a characteristic of the tumor Latent potential for malignant transformation

Grade III: Anaplastic Astrocytoma Grade IV: Glioblastoma multiforme Grades III and IV are high-grade gliomas 55% of gliomas Peak incidence middle to late adulthood

MANAGEMENT FOR GLIOMAS

Prognosis of Astrocytomas Median survival GBM: 1 year Anaplastic astrocytoma: 3 years Low-grade astrocytoma: 5 years Most die from transformation of tumor to higher grade

Oligodendroglioma Derived from oligodendrocytes or their precursors Oligodendrocytes produce the white matter in the brain 5-7% of all intracranial gliomas. Frequently with calcifications. Frontal lobe Most often in the 3rd and 4th decades Highly infiltrative Round regular “fried-egg” cells

“fried egg cells of oligodendroglioma”

Prognosis of Oligodendroglioma Median Survival Low-grade oligodendrogliomas: 8-16 years Anaplastic oligodendrogliomas: 5 years Tumors that have 1p/19q LOH—best prognosis Many patients die from malignant transformation of the tumor

Ependymoma Arise from ependymal cells (an intraventricular tumor) More common in children Most common in the 4th ventricle Spinal lesions more common in adults Intracranial ependymomas predominate in children

Prognosis 10-year survival: 47-68% Better prognosis: Young age Infratentorial Gross total excision Low-grade histology

MENINGIOMA Second most common primary brain tumor. Originate from arachnoid cap cells (meningoepithelial cap cells normally seen in arachnoid villi). 20% of all intracranial tumors (with asymptomatic cases—40% or more). Less than 1 cm per year (very slow growth but can recur) Tumor doubling time: 1.27 to 14.35 years

MENINGIOMA

MENINGIOMA Most diagnosed in 6th % 7th decades Female: Male—3:2 to 2:1 Multiple in 5-15% (NF-2) 90% intracranial 10% intraspinal Spinal meningioma: 10x in women All familial meningiomas occur with NF-2. Rare in children (more in boys) - Rare with dural attachments - Usually Intraventricular or posterior fossa - Frequently with NF-2

ESTROGEN receptors in meningioma - Expressed in 80% of women with meningiomas - Expressed in 40% of men with meningiomas Hormonal therapy

Management: Surgery Complete excision may cure many meningiomas The extent of resection is the most important in determining recurrence For recurrence: reresection

Radiation Therapy for meningioma Residual tumor after surgery Recurrent tumor Atypical or malignant histology

TUMORS OF THE PITUITARY GLAND Third most common primary brain tumor Often asymptomatic Incidence at autopsy: 1.7 – 24% Most common in adults in the 3rd and 4th decade

Pathology Microadenoma Macroadenoma - Less than 1cm - Symptoms due to excess hormone secretion (or hyperfunctioning) a. Growth hormone b. Gonadotropin c. Thyroid hormone d. Adrenal hormone e. Prolactin hormone Macroadenoma - More than 1cm - Symptoms due to compressing normal pituitary gland and neural structure causing hypofunctioning

Pathology Endocrine Active (Secretory) Prolactinoma Most common secretory intrasellar endocrine active tumor Secreted either by microadenoma or macroadenoma Growth hormone Before closure of epiphysis ® gigantism After closure of epiphysis ® acromegaly ACTH: Cushing’s Syndrome FSH and LH Endocrine Inactive (Non-secretory or null cell adenoma)

Histological characteristics: Almost all are histologically benign Pituitary CA: rare

Pituitary Carcinoma Highly invasive Rapidly growing & anaplastic Diagnosis relies on presence of distant metastasis

Clinical Manifestations of Tumors of the Pituitary Gland Compression of neural and vascular structures Headache Hypopituitarism Visual symptoms visual loss visual field abnormality: bitemporal hemianopsia is the most common Papilledema is rare 5% of pituitary adenoma present with pituitary apoplexy

VISUAL FIELD PATHWAYS

bitemporal hemianopsia

Pituitary Apoplexy Hemorrhage or infarction of pituitary adenoma Sudden onset of headache, nausea, vomiting, visual loss, diplopia, altered mental status Diagnosis by CT or MRI Treatment emergency surgery

Treatment Surgery Hormone replacement Radiation Treatment Radiosurgery

Medulloblastoma (MB) Most common malignant primary brain tumor of child age group. Small cell embryonal tumor of the cerebellum. Usually arise in the cerebellar vermis in the region of the apex of the 4th ventricle. Often presents with signs and symptoms of hydrocephalus. All Medulloblastomas are WHO grade IV.

Epidemiology Overall account ~ 7% all brain tumors. 10-20% of brain tumors in pediatric age group. 40% of tumors of the posterior fossa. Peak incidence at the age of 5 –6 yrs In children and 25 yrs in adults. male : female (3:2)

Raised ICT: Due to obstructive or non communicating hydrocephalus Clinical Features Raised ICT: Due to obstructive or non communicating hydrocephalus

Clinical features….cont’ Presenting symptoms are related to the age of the patient. infants (with open cranial sutures): irritability, anorexia, failure to thrive, macrocephaly and setting sun sign. The younger, nonverbal patient presents with behavioral changes, listlessness, irritability, vomiting, and decreased social interactions. Older children and adults headache, especially upon awakening in the morning.

Combination of: Surgery Radiotherapy chemotherapy Treatment: Combination of: Surgery Radiotherapy chemotherapy

Hemangioblastoma -Highly vascular , well circumscribed solid or cystic tumor of the CNS or retina. -The most common primary intra-axial tumor of the posterior fossa in adult. -May occur sporadically or as a part of vHL syndrome (in 20% of the cases). -May be associated with polycythemia

epidemiology 1-2.5 % of all intracranial tumors. Sporadic cases tend to occur in the 4th decade of life , while cases associated with vHL syndrome tend to occur early.

presentation Signs and symptoms of cerebellar Hemangioblastoma are those of post.fossa mass lesion: Headache Nausea and vomiting Cerebellar signs Obstructive hydrocephalus

Cns lymphoma May be primary or secondary. Suspected with homogenously enhancing lesion. Diagnosis highly likely if tumor seen in conjunction with uveitis. Primary B-cell lymphoma.

Conditions with increased risk of primary CNS lymphoma: Collagen vascular diseases. Immunosuppression In transplanted patients. AIDS (PCNSL occur in 10 % of AIDS patients) Epstein – Barr virus (associated with almost 100 % of PCNSL)

METASTATIC BRAIN TUMORS Cerebral metastases are the most common brain tumor seen clinically, comprising slightly more than half of brain tumors. 15-30% of patients with cancer (Ca) develop cerebral mets.

primary tumor was never identified percentages of patients developing brain metastases for specific primary histologies: lung cancer18-64% breast cancer 2-21% melanoma 4-16% % colorectal cancer 2-12 Kidney 1-8% thyroid 1-10% unknown primary 1-18% In up to 26% of cases, the primary tumor was never identified

Secondary tumors CT MRI

Spinal tumors