Brain Tumours Overview

Brain Tumours - Overview

• Prevalence: Brain tumours account for 2% of all cancers. In children under 15, they are the leading cause of cancer death.
• Types: Primary (originate in the brain) or secondary (originate elsewhere and spread). Examples of secondary sources include lung, breast, and melanoma cancers.
• Presentation: Characterised by symptoms/signs of increased intracranial pressure, seizures, signs of hydrocephalus, and focal neurological deficits.
• Metastasis: Primary brain tumours rarely metastasize (spread).
• Prognosis: Prognosis not solely based on tumour grade, but also on the tumour site, which significantly impacts resectability (surgical removal).

Learning Outcomes

• Classification: Understand the rationale behind classifying brain tumours and the significance of their varied biological behaviours.
• Biological Differences: Explain the biological variations between brain tumours and other body tumours.
• Cerebral Oedema: Explain the causes and consequences of localised and generalised brain swelling (oedema).
• Intracranial Pressure: Explain the effects of elevated intracranial pressure.
• Pathophysiology: Describe the mechanisms of abnormal water accumulation in the brain.
• Hydrocephalus: Discuss hydrocephalus, a condition involving excessive cerebrospinal fluid in the brain's ventricles.

Primary Brain Tumours

• Cell Types: Include tumours arising from meninges, neurons, glioma, pineocytomas, pituitary adenoma, embryological remnant cells, nervous tissue, and primitive/precursor cells.
• Embryonal Tumours: Medulloblastoma and other embryonal tumors arise from primitive or immature cells in the developing brain and are commonly located in the cerebellum or brainstem, frequently affecting children. Craniopharyngiomas, on the other hand, originate from embryonic tissue, usually in the pituitary gland.
• Neuroglia: Most common brain tumours are derived from glial cells (astrocytes and oligodendrocytes), often referred to as gliomas.

Grading of Brain Tumours (Glioma)

• WHO Grade I: Defined by specific type (e.g., pilocytic astrocytoma). Excellent prognosis (5-year survival rate >95%).
• WHO Grade II: Absence of high-grade features. Median survival around 10 years.
• WHO Grade III: Presence of mitosis (cell division). Median survival between 3 and 5 years.
• WHO Grade IV: Mitosis, microvascular proliferation, and necrosis. Survival is usually measured in months with a 5-year survival rate of less than 5%.

Molecular Neuropathology

• Diagnostic Adjunct: Useful for making diagnosis or grading tumour type.
• Predictive Value: Can predict responsiveness to therapy.

Common Molecular Abnormalities

• BRAF: Important in pilocytic astrocytomas; BRAF inhibitors can be therapeutic
• IDH1/2, 1p19q co-deletion and MGMT methylation: Relevant molecular markers used in glioma and other tumour types frequently correlating to prognosis.
• Histone H3: Mutations within this protein can indicate aggressive (high-grade) types of glioma.
• Isocitrate dehydrogenase (IDH): Mutations can lead to tumorigenesis through altered DNA methylation and gene expression. IDH mutations often correlate with less aggressive forms of tumours.
• MGMT (O6-methylguanine-DNA methyltransferase): Methylation is associated with improved response to temozolomide treatment.

Targeted Therapies

• NTRK Fusions: NTRK fusion proteins promote cancer growth and division and are a target for therapies such as larotrectinib and entrectinib.

Case Studies

• Case 1 (14-year-old): Diffusive midline glioma with H3K27M mutation, WHO grade 4. The significant presence of this mutation is an indicator of high-grade malignancy.
• Case 2 (39-year-old): Oligodendroglioma grade II, with 1p19q co-deletion and IDH1/2 mutation. This case provides examples of how genetic markers define specific tumour types.
• Case 3 (1-year-old): Atypical teratoid/rhabdoid tumour (AT/RT), WHO grade IV. This case relates to understanding malignant embryonal tumours. Key features are the poorly differentiated cells' characteristics with diverse origins and the presence of SMARCB1 mutation.

Intracranial Pressure (ICP)

• Compartment: The brain is enclosed within a rigid skull.
• Compensatory Phase: Initially, cerebrospinal fluid (CSF) shifts to the spinal cord, and blood volume decreases in cerebral veins. When this initial phase persists, increased swelling causes vascular compression and insufficiency, leading to raised ICP.
• Causes: Cerebral edema, hydrocephalus, and tumours.
• Symptoms: Headaches (often worse when lying down or in the early parts of the day), nausea/vomiting (especially in children), decreased consciousness/coma, and swelling of optic nerve head (papilloedema).

Cerebral Herniation

• Forces brain tissue to move from one compartment to another.
• Types and Causes: Uncal (temporal lobe), central, and tonsillar herniation are the different types; usually owing to elevated intracranial pressure (ICP).
• Compression: Brain tissue shift causes further compression, disrupting its function and blood supply.
• Vascular Compression: Herniation can compress blood vessels, which leads to vascular ischemia and tissue death (infarction)

Hydrocephalus

• Causes: Increased cerebrospinal fluid (CSF) volume within the brain's ventricular system. This can result from overproduction (e.g., choroid plexus tumours). or inadequate absorption (e.g., blockage of arachnoid granulations). or both. Interference with CSF flow (common), like neoplasm, malformations, infections, or haemorrhage/gliosis, can also cause hydrocephalus.
• Symptoms: Infants with hydrocephalus typically present with a rapidly enlarging head circumference, bulging fontanelles (soft spots on the skull), and other symptoms like vomiting, irritability, sleepiness, and abnormal eye movements ('sunset eyes').

Cerebral Oedema

• Vasogenic oedema: Caused by increased vascular permeability of the blood-brain barrier. Fluid leaks into the brain tissues.
• Cytotoxic oedema: Occurs due to cellular dysfunction, often resulting from neuronal/glial/endothelial injury (e.g., lack of oxygen). Cellular swelling due to the failure of pumps, like Na+/K+ ATPase (a sodium-potassium pump), and abnormal water and electrolyte movement.

Rhabdoid Tumor Predisposition Syndrome (RTPS)

• Diagnosis: Characterised by presence of rhabdoid tumors, particularly if multiple primary tumors are present, or if there is a family history.
• Additional features: Supporting evidence includes additional malignant entities such as cribriform neuroepithelial tumors, peripheral nerve sheath tumors, and non-malignant schwannomas or meningiomas.
• **Gene mutations:**Germline mutations in SMARCB1 or SMARCA4 highlight the role of these genes in the development and progression of brain tumors.

Brain Tumors and Cancer Family Syndromes

• Association: Several specific cancers are linked to known cancer-prone syndromes. These associations demonstrate that specific genetic profiles can increase susceptibility to specific brain and other tumours.
• Examples: Neurofibromatosis, von Hippel-Lindau disease, tuberous sclerosis, Li-Fraumeni syndrome, Cowden syndrome, and Turcot syndrome are all associated with increased susceptibility to specific tumors.

This quiz offers an essential overview of brain tumours, their prevalence, types, and presentation. You'll learn about primary vs. secondary tumours, the implications of metastasis, and factors affecting prognosis. Additionally, you'll explore the classification of brain tumours and their biological differences compared to other cancers.