Brain Tumours

Brain Tumours

Epidemiology

·        2% of all cancer deaths

·        20% of paediatric neoplasms (21 per 100,000 at 2 years)

·        Incidence 8 – 10 per 100,000 per year

·        Incidence lowest in teens rises to 16 per 100,000 in 70‟s

Histology

·        Cell types in the brain: neurons, microglia (lymphocytic derived, phagocytic function), oligodenrocyte (myelination), choroid cells (make CSF), astrocytes (structural support, star shaped, multiply in sites of injury), ependymal cells (line ventricles), meninges, pituitary, lipophages (histiocytes which phagocytose lipid rich myelin – non-specific marker of white matter destruction)

·        Neuropil = intercellular matrix in the CNS – tangled processes of neurones, astrocytes, oligodendrocytes

·        Tumour ® vasogenic oedema

·        Incidence of neoplasms:

o   Neuroepithelial (ie intrinsic brain cells) ® Gliomas: 52%

§  Astrocytoma: 44%. When severe = Glial Blastoma Multiforme (GBM)

§  Ependymoma 3%

§  Oligodendrioglioma: 2%

§  Medulloblastoma: 3%

o   Metastatic 15% (eg breast, lung)

o   Meningioma: 15%

o   Pituitary: 8%

o   Vestibular Scwhannoma: 8%

o   Also retinoblastoma

·        Different incidence in children: 

o   Normally posterior fossa (as opposed to anterior fossa in adults) and different frequencies of different types

o   Most common tumours are pilocytic astrocytoma and medulloblastoma

Astrocytoma

·        Locally invasive

·        Presentation:

o  ­ICP from obstructive hydrocephalus and from space occupying lesion

o  Focal neurological deficit

o  Epilepsy: ¾ of high grade astrocytoma present with seizure

o  Endocrine

·        By age:

o  Cerebral hemispheres in middle and old age

o  Spinal cord in young adults

o  Cerebellum and pons in childhood

·        Pathology:

o  Benign = won‟t recur if removed.  However, also need to be accessible to have a good prognosis

o  Heterogeneous – range from well-differentiated to anaplastic

o  Characteristic fibrillary background of cytoplasmic processes containing Glial Fibrillary Acidic Protein (GFAP). Can use immunohistochemistry to stain for these. May congregate to form Rosenthal fibres

o  Graded from 1 (low grade, and hard to differentiate from reactive gliosis although these rarely produce a distinct mass) to 3 (anaplastic) to 4 (glioblastoma multiforme – GBM, mitoses common compared with low grade, pallisading necrosis differentiates it from grade 3). Low grade have a tendency to become high grade and are also hard to cure due to their infiltrative nature

o  Grossly: Infiltrative. Either firm or soft/gelatinous. GBM is heterogeneous with focal haemorrhage and necrosis

o  Pilocytic variant of astrocytoma: most common astrocytoma of childhood. Excellent prognosis. Cystic. Usually in cerebellum

o  Astrocytomas (grade 3 or 4) are the most common gliomas to arise subsequent to radiotherapy (usually 5 – 25 years later)

·        Investigations: CT and MRI.  Xray and angiography obsolete

·        Management:

o  Dexamethasone: ¯vasogenic oedema ® ¯ ICP

o  Anticonvulscents ® ¯seizures

o  MR spectroscopy ® biopsy by framed stereotactic or image guidance 

o  Surgery: debulking or macroscopic excision (only if not deep or eloquent areas otherwise too much damage from surgery – use radiotherapy for these) 

o  Arguments for macroscopic excision. High-grade gliomas weigh 100g at diagnosis = 10E11 cells. After macroscopic excision will still have 10E10 cells. Effective radiotherapy ® 10E8 cells. Chemo/radio therapy only kills cells in division

Prognosis

·        For GBM:  Median survival:

o  Without surgery, 17 wks

o  With surgery, radio and chemo, 51 wks

·        For low grade glioma: 50% 5 year survival if total macro excision

Other Neuroepithelial Tumours

·        Subendymal giant cell astrocytoma: associated with tuberous sclerosis

·        Neuronal tumours: not common.  Include:

o  Gangliocytomas

o  Gangligliomas: better prognosis

o  Cerebral neuroblastoma: Rare, in children. Resemble peripheral neuroblastomas – „small round blue-cell tumours‟

·        Oligodendroglioma:

o  5 – 15% of gliomas

o  Radiographically, well demarcated and often show calcification (key differential)

o  Grossly: gelatinous masses +/- cysts and/or haemorrhage

·        Ependymoma: usually in fourth ventricle ® outflow obstruction. Also in intramedullary portions of the spinal chord. Slow growing and not malignant but poor prognosis. CSF spread is common.

·        Significant histological features: „true‟ rosette and perivascular pseudo-rosette.  Numerous subtypes

·        Choroid Plexus Papilloma: rare. In ventricles. Usually children. Cauliflower type projections into ventricular lumen

·        Pineal Neoplasma: Intrinsic tumours are Pineocytoma and Pineoblastoma. Germ cell tumours are the most common, including choriocarcinoma, teratoma, etc. Present with mass effects in men aged 20 – 40. Differential: lymphoma or metastatic cancer

·        Hemangioblastoma: Highly vascularised, cystic tumours, mainly in the cerebellar hemispheres

·        Craniopharyngioma: Arise from the epithelium of Rathke‟s pouch – part of the embryonic nasopharynx the forms the anterior lobe of the pituitary. Present due to mass effects in children and adolescents. Histology: see keratin pearls.

·        Primitive Neuroectodermal Tumours (PNETS):

o   Rare tumours in children arising from primitive glial or neuronal precursor cells. Aggressive and poor prognosis. Usually “small round blue-cell tumour” (differential includes lymphoma)

o   Medulloblastoma: a distinctive PNET. Occurs exclusively in the cerebellum, mainly in children, mainly as a midline mass. Cause CSF obstruction and spread via CSF

·        Scwhannoma: In the cranial vault, nearly all schwannomas are attached to the 8^th cranial nerve in the cerebellar pontine angle Þ acoustic neuroma

·        Lymphoma: Either originated in the CNS or from systemic invasion (usually affect the meninges). Usually B-cell lymphomas

Pituitary

·        Pituitary Adenoma: benign neoplasm in anterior lobe of the pituitary

o   Present with either mass effects (including on the rest of the pituitary) and excess hormone secretion

o   At any age or sex, but most common in men aged 20 – 50

o   Classified on the basis of hormones they secrete by immunocytochemistry. Poor correlation between acidophils, basophils and chromophobes and the hormones secreted

·        Carcinomas are rare.  Diagnosis requires gross brain invasion or discontinuous spread

Metastatic Brain Tumours

·        20% have intracranial mets at autopsy

·        In 15% primary organ not found

·        Surgery for solitary met if primary site controlled or for symptomatic control or for diagnosis 

·        Most mets are carcinomas. 80% are due to (in decreasing frequency): lung, breast, skin (melanoma), kidney and GI 

·        Prognosis:

o   Melanoma & lung solitary: < 30% 1 year survival

o   Breast solitary: 50%

o   Undetermined solitary: 50%

Meningioma

·        20% of primary intracranial neoplasms

·        Incidence peaks in females aged 40 - 50

·        Benign in 90 – 95%

·        Occur anywhere round brain

·        Well circumscribed ® mass effects

·        Histology: meningothelial whorls and psammoma bodies

·        Tx: surgical excision