CNS tumours Flashcards
Describe the cells of the CNS
- Neurons: Functional component (conduct impulses)
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Glial Cells: Support and protect neurons. Main types:
- Astrocytes: Provide metabolic support to neurons, form the blood-brain barrier, and are important for repair and scarring of nervous tissue.
- Oligodendrocytes: Produce myelin surrounding the neurons in white matter.
- Ependymal Cells: Line ventricles and may have both secretory and absorptive functions. Modified ependymal cells form the choroid plexus and produce CSF.
- Microglia: Macrophages in the CNS.
List other cells in the CNS
- Meningothelial (form meninges)
- Pineocytes (pineal gland)
- Epithelial cells (pituitary)
- Endothelial cells (line blood vessels)
- Schwann cells (surround cranial nerves)
- Lymphocytes
- Germ cells (aberrantly migrated germ cells in midline in males)
Also: pituitary adenomas
Contrast intra and extra axial tumours
- Intra-Axial Tumours: Occur in brain or spinal cord parenchyma (e.g., astrocytoma, oligodendroglioma, medulloblastoma).
- Extra-Axial Tumours: Occur external to brain/spinal cord parenchyma (e.g., meningioma, pituitary adenoma, cranial nerve schwannoma, metastases).
Describe the characteristis of neoplasms in CNS
- The distinction between benign and malignant neoplasms is less distinct in the CNS because either are space-occupying lesions, which is the real source of agony with CNS neoplasms, impinging on normal CNS parenchyma
- however it does have significance re: surgical prognosis
- Most malignancies of the CNS do not metastasize outside of the CNS.
- The subarachnoid space and the CSF provide a pathway for seeding of neoplasms that reach the CSF pathway.
Why are brain tumours bad?
- Even a “benign tumour” can have severe consequences if in an unresectable or vital location.
- Tumours don’t have to metastasise to kill – affect vital structures
- may be unresectble
- surgery is a balance of consequence to patient vs benefits of debulking
- often diffuse or multifocal, difficult to resect with good margins
- good margin will involve removing vital tissues, with bad consequences
- BBB: therapeutic consequences
Describe the WHO grading system for astrocytoma
- Good Prognosis vs. Poor Prognosis
- Factors:
- Atypia i.e. cellular
- Mitoses
- Endothelial proliferation
- Necrosis (palisaded)
- Other factors (cellularity, molecular, etc.)
In general higher grade means poorer differentiation and prognosis.
- Grade I tumors: Circumscribed (encapsulated or not) and exhibit mild increase in cellularity
- Grade II tumors: Moderate increase in cellularity, but their margins are poorly-defined or diffuse
- Grade III tumors: Increased cellularity, moderate cellular pleomorphism, and mitosis
- Grade IV tumors: Marked pleomorphism and show microvascular proliferation and/or pseudopalisading necrosis
- Gd 1: Low proliferation, possibility of cure following LR; grade stable
- Gd 2: High cellularity, recur as infiltrative; may be grade unstable, i.e., progression
- Gd 3: More aggressive recurrence with shorter time to demise; often require adjuvant chemoradiation
- Gd 4: Aggressive, high proliferation, rapid growth, usually fatal outcome – some tumors may still be curable with aggressive treatment
Describe astrocytoma
- 80% of adult primary brain tumors
- Usually found in cerebral hemispheres
- Most often in 4th - 6th decades
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Presenting signs and symptoms:
- Seizures
- Headaches
- Focal neurologic deficits related to the anatomic site of involvement
- Grade 2 astrocytoma: Increase cellularity but no pleomorphism, mitosis, or necrosis
- Grade 3 astrocytoma: Increase cellularity, pleomorphism, and mitosis
- Grade 4 (either astrocytoma, IDH-mutant grade 4, or glioblastoma, IDH-wildtype): Marked pleomorphism, microvascular proliferation &/or pseudopalisading necrosis
- Glioblastoma Multiforme: Variegated appearance with necrosis and hemorrhage
- Pseudopalisading necrosis
- Glomeruloid microvascular proliferation
Describe pilocytic astrocytoma
- Most common in cerebellum
- Grade 1 astrocytoma…slow growing…good prognosis
- Piloid gliosis & eosinophilic granular bodies
- Treated with only surgery
- described on imaging as cystic lesion with mural node
Describe astrocytoma prognosis
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Two most powerful prognostic variables are:
- Age: inversely proportional to survival time
- Tumor grade
- Lower grade tumor may become more anaplastic (higher grade) with time (secondary gliomas)
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Poor prognostic factors:
- Higher grade
- Necrosis
- Older age (>45 y)
- Incomplete resection
- Prognosis for glioblastoma is very poor <6 months (variable response to treatment - most patients die within 15-18 months with chemoradiation)
Describe molecular pathology for astrocytomas
Molecular Pathology
- Integration of molecular profile into tumor definitions
- Morphology is important, but definitive diagnosis of many tumor types needs detection of specific genetic changes
- Enough tissue and time are needed to test for these changes
- Adult-type diffuse gliomas now divided into:
- Astrocytoma, IDH-mutant: responds better to therapy
- Glioblastoma, IDH-wildtype – grade 4 tumor with worse prognosis
- Oligodendroglioma, IDH-mutant and 1p/19q codeleted
Molecular Oncology
- IDH1 & IDH2 mutations: Present in astrocytomas, IDH-mutant and oligodendrogliomas
- ATRX mutation: Common in astrocytoma, IDH-mutant
- Molecular alterations in glioblastoma, IDH-wildtype do not have IDH mutations, usually lack ATRX loss
Molecular Oncology, Continued
- Molecular alterations in glioblastoma, IDH-wildtype: EGFR amplification, TERT promoter mutations, Chromosome 7 gain and chromosome 10 loss
- presence of these : straight to grade 4
Molecular Oncology – A Brief Sidetrack
- O6 methylguanine DNA methyltransferase (MGMT) promoter methylation: Favorable prognostic marker in high-grade glioma, detectable with PCR
Describe oligodendroglioma
- Frequency: 5% to 15% of gliomas
- Age Group: Most common in the 4th to 5th decades
- Symptoms: Several years of neurological complaints, often including seizures
- Location: Mostly in cerebral hemispheres, with a predilection for white matter
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Growth Pattern: Typically slow-growing
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Unique Features:
- Calcification due to slow growth
- Delicate ‘Chicken wire’ vessels
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‘Fried egg’ appearance to cells
- Round nuclei
- Perinuclear halo
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Unique Features:
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Images:
- Chicken wire vessel pattern
- Fried egg appearance:
Pathology/Molecular Biology
- Prognosis: Better than patients with astrocytomas
- Survival: Average of 5 to 10 years
- Treatment: Combines surgery, chemotherapy, and radiotherapy
- Cytogenetic Abnormality:
- 1p and 19q deletion: Excellent response to treatment
- Without 1p and 19q deletion: Refractory to treatment
- Diagnostic Tool: Fluorescent In Situ Hybridization showing loss of 1p19q
Describe ependymoma
- Frequency: 3-9% of gliomas
- Origin: Arises from the ependymal lining of the ventricular system or spinal cord
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Age Group:
- Children: 5% to 10% of primary brain tumors, often near the fourth ventricle
- Adults: Commonly in the spinal cord, especially with neurofibromatosis type 2
- Symptoms: Often related to obstruction of CSF flow
- Microscopy: Perivascular rosettes, true ependymal rosettes, and papillary structures; may also see exophytic growth projecting into vent cavity
- Prognosis: Often poor despite slow growth and lack of histologic evidence of anaplasia; CSF dissemination is common; average survival of about 4 years post-surgery and radiotherapy
Describe choroid plexus papilloma
- Age Group: Common in children (lateral ventricles), rare in adults (4th ventricle)
- Symptoms: Presents as hydrocephalus
- Possible Etiology: Papovavirus
Broadly describe neuronal tumours
- Types: Gangliocytoma, Ganglioglioma, Neurocytoma
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Characteristics:
- Mature tumors resemble mature cell types - gang and neuro –> name depends of % of ganglion cells; appears in children, can present with epilepsy
- Primitive neuronal tumors (e.g., Medulloblastoma, PNET) are immature, resembling fetal cell types
Describe gangliocytoma or ganglioma
- Composition: Well-differentiated/mature neuronal cells (ganglion cells)
- Frequency: Rare, 0.4% of all CNS tumors
- Age Group: First 3 decades of life (8-25 years)
- Location: Occurs anywhere in the brain, commonly in the temporal lobe
- Symptoms: Indolent or may present with protracted partial complex epilepsy
Describe neurocytoma
- Composition: Highly differentiated diminutive neuronal elements
- Location: Intraventricular tumor, possibly arising from the septum pellucidum
- Age Group: Adults 20-40 years
- Prognosis: Generally good, unless there’s invasion of periventricular structures or dissemination via CSF
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Microscopy
- small round uniform cells
- salt and pepper chromatin
- resemble oligodendroma
- shows neuronal lineage
- positive with synaptophysin
Describe medulloblastoma
- Age Group: 70% under 16 years, mean age 7 years, more common in males
- Location: 75% in the cerebellum’s vermis
- Symptoms: Truncal ataxia, headache, CSF obstruction - disseminates easily into spinal cord
- Microscopy: Hypercellular tumor, several mitoses, Homer Wright rosettes
- Prognosis: Highly malignant, dismal for untreated patients, exquisitely radiosensitive tumour, 5-year survival 50-70% with treatment
- poor prognostic factors include being under 3 years, metastases and presentation and incomplete resection
- treatment involves a combination of surgery, radio and chemotherapy
- causes short and long term complications
Briefly describe other parenchymal tumours
- Include: Primary CNS Lymphoma, Germ Cell Tumors, Schwannoma, Metastatic Tumors
- Primary CNS lymphoma: 2% of extranodal lymphomas and 1% intracranial tumours – most common in CNS neoplasm in immunosuppressed e.g. AIDS and post transplantation. no need for debulking. Use chemotherapeutic agent
- GC tumours occur along midline mostly pinear and suprasellar regions, tumour of young: 90% in first two decasdes; 0.2-1% in Europeans, 10% in Japanese
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Meningioma: 20% of primary intracranial tumors, age 40-70 years, more common in females, especially in the spine. Usually attached to dura
- arises from meningothelial cells of arachnoid granulations
- extra axial
- slow growing
- WHO grade a strong predictor of clinical course, typically low grade
- prognosis depends on size and completeness of resection
- macro: firm and rubbery (due to connective tissue)
- micro: whorls of meningothelial cells, psammomma bodies (calcified)
- Schwannoma: 8% of intracranial and 29% of intraspinal tumors, common in 4th-6th decade, associated with NF-2; arises from spinal and cranial nerves esp. 8th i.e. acoustic neuroma, slow growing and rarely malignant; NF-2 (Schwannomatosis = bilateral acoustic neuromas and meningiomas)
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Metastatic Tumors: Mostly carcinomas, 25-50% of intracranial tumors, meninges a frequent site of involvement by metastatic disease; 80%/common sites of origin include lung, breast, skin (melanoma), kidney, and GI tract
- metastatic tumours may be first manifestation of cancer
- some metastases can present with intracranial haemorrhage e.g. melanoma and RCC
