Brain Histology and Pathologies

Normal Brain Histology

• Key histological features include neurons, neuroglia (glial cells), neuropil, and capillaries.
• Neurons are excitable cells that transmit electrical signals.
• Neuroglia includes astrocytes, microglia, ependymal cells, and oligodendrocytes.
• Astrocytes aid in scar formation and the blood-brain barrier (BBB).
• Microglia are involved in phagocytosis.
• Ependymal cells produce cerebrospinal fluid (CSF).
• Oligodendrocytes are responsible for myelination.

Brain in Pathological Conditions

• Two chromatolytic cell bodies can be adjacent to a normal cell body.
• Major pathologies include infections/inflammations, vascular diseases, metabolic disorders, and tumors/neoplasms.
• Metabolic disorders can include hypertensive encephalopathies, glucose disorders, and parathyroid disorders.
• Common exogenous causes of toxic encephalopathy include alcohol-related disorders, industrial agents and inhaled gases.

Brain Pathologies

• The location of a lesion or tumor leads to specific signs and symptoms.
• Common brain tumor symptoms include seizures, personality changes, nausea, headache, and fatigue.
• Pre-malignant & in-situ stage and High/Low grade are tumor characteristics.

Common Tumors

• Intracranial neoplasms include glioblastoma, oligodendroglioma, meningioma, and brain metastasis.
• Paediatric Tumours include medulloblastoma and retinoblastoma.
• Nerve sheath tumours include schwannoma and neurofibroma.

Brain Tumours Basics

• Risk Factors include age and radiation.
• Increased risk with age correlates with shorter telomeres.
• Radiation exposure increases the risk of meningiomas and gliomas.

Brain Tumours

• Primary brain tumours originate in the brain from cells within the brain parenchyma or extra neural structures.
• Secondary brain tumors (brain metastases) originate in tissues outside the brain and spread to the brain.

Brain Tumours: Cell of Origin

• Astrocytes can give rise to pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma.
• Oligodendrocytes can lead to oligodendroglioma.
• Ependymal cells can result in ependymoma.
• Embryonal cells can cause medulloblastoma.
• Meninges can produce meningioma.
• Cranial nerves can lead to acoustic neuroma.

Brain Tumours: Biological Behaviour

• Brain tumors can be benign or malignant.
• Brain tumors cause symptoms through invasion and destruction, direct compression, increased intracranial pressure, and obstruction of dural venous sinuses, CSF drainage or absorption.

Gliomas: Astrocytoma

• Gliomas are graded from I-IV, with Grade IV being glioblastoma and diffuse midline gliomas.
• Pilocytic astrocytoma (Grade I) has benign cytological features.
• Diffuse astrocytomas (Grade II) have moderate cellularity with no anaplasia or mitotic activity.
• Anaplastic astrocytomas (Grade III) show cellularity, anaplasia, and mitoses.
• Glioblastoma and diffuse midline gliomas (Grade IV) share Grade III features plus microvascular proliferation and necrosis.
• Surgery and radiotherapy are potential treatments.

Glioblastoma Characteristics

• Key pathological characteristics include necrosis, pseudo-palisading of tumor nuclei, vascular or endothelial proliferation, and lymphocytic "cuffing" around blood vessels.
• Systemic metastasis of glioblastoma multiforme (GBM) is rare.

Glioblastoma Management

• Chemo- Temozolomide (Alkylating agent)
• Anti-angiogenesis*- Bevacizumab
• Poor prognostic factors include increased age, increased necrosis, and deep location.

Gliomas: Oligodendroglioma

• Slow-growing gliomas.
• Mutations in isocitrate dehydrogenase (IDH) genes are significant.
• A diagnostic chromosomal deletion is of the p arm of chromosome 1 (1p deletion) or of the q arm of chromosome 19 (19q deletion).
• Most common in forebrain frontal lobes.
• Like astrocytomas, oligodendrogliomas can evolve into more aggressive forms, such as anaplastic oligodendrogliomas (WHO grade III)
• Can appear with seizures (new-onset)

Gliomas: Oligodendroglioma - Pathology

• Characterized by calcifications, fried egg appearance of cells, microcystic degeneration, and chicken wire appearance of capillaries.
• Prognosis is 10-20 years with treatment II and III for 5-10 years.
• Better prognosis includes younger age, gross total tumour resection, postoperative radiation therapy.

Differential Diagnosis of New-Onset Seizure

• Toxicologic etiologies include alcohol withdrawal, cocaine, isoniazid, and theophylline.
• Metabolic abnormalities to consider are hypoglycemia/hyperglycemia, hyponatremia/hypernatremia, and hepatic encephalopathy.
• Serum blood glucose and serum electrolytes are investigations to order.

Meningioma

• Almost always benign, slow-growing brain tumors arise from arachnoid cap cells of the arachnoid villi.
• Predisposing factors include female gender, presence of hormone receptors, familial syndromes, and radiation-induced factors.
• Meningioma's tend to infiltrate bone, which is thickened.

Meningioma: Radiological Findings

• Radiological findings: Round and usually well-circumscribed mass attached to dura.
• A cellular mass without necrosis occurs.

Meningioma Key Pathological Features

• Round and well circumscribed mass.
• Well circumscribed mass with some angiogenic changes.
• Tumor separates readily from surrounding brain tissue, elongated cells.

Meningioma: Arising Locations

• Benign which are usually are in nature; however, a small percentage are malignant.
• Many types of meningiomas are asymptomatic.
• Symptomatic meningiomas are treated with surgery.
• Can cause visual field defects or anosmia.

Peripheral Nerve Sheath Tumours: Schwannomas

• Benign tumors arise from Schwann cells in the nerve sheath.
• Can originate from cranial nerves, peripheral nerves, and the sympathetic trunk.
• Vestibular schwannomas almost always arise from the vestibular division of the 8th cranial nerve.

Schwannoma Details

• Firm gray mass attached to nerve, but no invasion
• Radiology: Well circumscribed and encapsulated mass in the paraspinal region.
• Gross: Mass is attached to the nerve, but is non-invasive
• Histology: Cells are uniformly spindled, hyper and hypocellular regions

Myxoid Schwannoma

• Schwannoma are more common than neurofibromas present usually as solitary tumours.
• Around 60-80% of nerve-sheath tumours arise from nerve roots before leaving the dural sac.

Neurofibromas

• Benign peripheral nerve sheath tumor can be a symptom of Neurofibromatosis type.
• Multiple neurofibromas are the distinguishing characteristic.
• 3 Subtypes, Localized cutaneous Neurofibroma, Plexiform Neurofibroma, and Diffuse Neurofibroma.
• Neurofibroma is a fusiform mass involving the whole nerve, while schwannoma exhibits an eccentric mass around the nerve.

Paediatric Tumours: Medulloblastoma Characteristics

• Most frequent in midline of cerebellum.
• Small cells around a central neuropil creating characteristic Homer-Wright rosettes.
• Tumor Dissemination commonly occurs via CSF.

Paediatric Tumours: Retinoblastoma

• The most common primary intraocular malignancy in children.
• sporadic or inherited mutations in the retinoblastoma gene
• Can be a white pupil due to reflection from chalky tumors (Leukocoria)

Ependymoma Characteristics

• The tumor arises from ependymal cells of the ventricular system.
• fourth ventricle is the most common location for tumors.
• Round to oval nuclei with a fibrillary background microscopically.
• Can cause perivascular pseudorosettes.

Cerebral Palsy

• Cerebral Palsy is loss or impairment of motor function.
• The neurological disorders that appear in infancy or early childhood affect body movement and muscle coordination.
• Spastic Cerebral Palsy can be diplegic where lower limbs more affected.

Shaken Baby Syndrome Triad

• Retinal hemorrhaging
• Brain swelling
• Subdural hematoma

Metastatic Brain Tumours

• Metastatic lesions from carcinomas in the lung, breast, skin (melanoma), kidney, and gastrointestinal tract, are common.
• Morphological features: Sharply demarcated lesions if the metastasis is within the brain parenchyma.
• Commonly seen at the junction between white and grey matter.