BMS100_PAT2-02_F2022 (1).pptx

Neuropathology 2 Brain tumours BMS 100 Week 13 Topics for today General considerations Types of primary CNS tumours: Gliomas Astrocytomas Oligodendrogliomas Ependymomas Meningiomas Neuronal tumours and medulloblastomas Common metastases to the brain Brain tumours – general considerations Epid...

Neuropathology 2 Brain tumours BMS 100 Week 13 Topics for today General considerations Types of primary CNS tumours: Gliomas Astrocytomas Oligodendrogliomas Ependymomas Meningiomas Neuronal tumours and medulloblastomas Common metastases to the brain Brain tumours – general considerations Epidemiology: • 10 - 17 per 100,000 for intracranial tumors • 1 to 2 per 100,000 for intraspinal tumors • about 50 – 75% are primary tumors – the rest are metastases from other organs • Account for 20% of all childhood cancers  70% of childhood CNS tumors arise in the posterior fossa • 70% of CNS tumours tend to arise above the tentorium cerebelli in adults Brain tumours – general considerations • Many seem relatively benign:  Grow slowly  Relatively well-differentiated (minimal anaplasia) • However, even a slow-growing, well-differentiated tumour in the brain can cause serious problems  Compression or destruction of smaller, critical brain areas such as the medulla  Tumours that are difficult to isolate from normal brain tissue can result in extensive destruction when they are removed  Damage to the blood-brain barrier or development of epilepsy due to the tumour or its removal • Aggressive, poorly differentiated brain tumours are among the deadliest of cancers Astrocytomas – the most common gliomas • Grades for astrocytomas range from I – IV  The higher-grade tumours (i.e. IV) exhibit: • greater anaplasia  Anaplasia = abnormal cellular morphology, greater rate of mitosis • greater invasion into the surrounding tissue • Increased necrosis and more sites of hemorrhage/BBB incompetence • Naming conventions for different grades: * know these  Grade  Grade  Grade  Grade I – pilocytic astrocytoma (commonly-used name) II – diffuse astrocytoma III – anaplastic astrocytoma IV – glioblastoma multiforme (commonly-used name) Grade I astrocytomas …aka pilocytic astrocytomas • Tend to occur in children and young adults • Often found in the cerebellum, optic nerves, 3rd ventricle • Can be a solid or a cystic mass – either way, the tumour is well-differentiated and relatively easy to separate from surrounding normal brain tissue  Cells often are large and have only two processes  Few hemorrhagic areas, less necrosis, preservation of BBB • Usually excessive activation of Raf (gene called BRAF) – remember receptor tyrosine kinases?  Like having a growth factor receptor constantly “turned on” Grade I astrocytoma in the cerebellum Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 28.49, p. Review Grade II & III astrocytomas • More common in adults, usually found above the tentorium in the cerebrum  Sometimes found in the cerebellum or medulla • Grade II – poorly differentiated cells, invade surrounding brain • Grade III – similar to grade II, but more mitotic figures, larger cells, more mitotic figures • Mutations include:  PTEN: inactivated PTEN  excessive signaling through the PI3K pathway  Increased EGF or PDGF receptor activity or expression • Epidermal growth factor, platelet-derived growth factor  P16, p14 or p53 inactivation  IDH mutations – isocitrate dehydrogenase mutations that produce a metabolite (2-hydroxyglutarate) that “dysregulates” epigenetic signaling in the glial cell  excessive activation of the RAS pathways Grade IV astrocytomas Aka glioblastoma multiforme • Unfortunately the most common brain tumour in adults – and has the worst prognosis  Prominent hemorrhage, necrosis, rapid growth  Tends to invade the adjacent tissue more than other types  p53, EGFR (epidermal growth factor receptor) mutations are more common Grade II astrocyto ma Grade IV astrocytoma • Necrotic, hemorrhagic infiltrating mass Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9 th ed. Fig Astrocytomas – Clinical Features • Signs and symptoms:  Headache (worse in morning), intensified by straining and coughing  Nausea, vomiting  6th cranial nerve palsy  Focal changes caused by invasion/damage of normal brain tissue • Seizures, hemiparesis, ataxia, memory loss… many • 80% of astrocytomas are Grade II – IV; majority are the more unpleasant ones  5–6-year median survival for Grade II, Grade II has a 10 – 20% 5year survival rate  Very poor (< 1 year) for Grade IV • Worse prognosis associated with:  Infiltration of normal tissue  Hemorrhage and necrosis  Rapid cell division Astrocytomas – Diagnosis & Treatment • MRI the best imaging method • Treatment depends on the type of tumour  Radiation, chemotherapy, surgery all commonly used Remember – signs/symptoms of increased intracranial pressure? • Slowing of mental capacity • headaches (especially if more severe in the morning) • vomiting (more likely in the morning) • blurred and/or double vision  blurred = optic nerve atrophy due to papilledema, double vision = 6th cranial nerve palsy (usually) • In kids – precocious puberty, stunted growth due to hypothalamic impairment • Difficulty walking (spasticity) Herniation due to increases in intracranial pressure or masses Brain tumours are common causes of brain herniations • Sub-falcine and transtentorial more likely with cerebral masses Kumar et. al., Robbins and Cotran Pathologic Basis of Dis 9th ed. Fig 28.3, p. 1245 Oligodendrogliomas • 5% to 15% of gliomas  most common in 40’s and 50’s • Pathogenesis:  Found in the cerebral hemispheres, around white matter areas  IDH mutations common  Cells often similar to normal oligodendrocytes, often surrounded by a capsule  Signs and symptoms typical of slowly increase in intracranial pressure  seizures are quite common • Diagnosis and treatment similar to that of astrocytomas • In general, prognosis is usually better than that of astrocytomas  Determined on a case-by-case basis Ependymomas • Arise from the ependymal cells of the ventricular system  Frequently block the central canal or are near the 4th ventricle in kids • They also can produce lots of CSF • Therefore, can cause communicating (excess CSF) or noncommunicating (blockage of CSF movement) hydrocephalus  In adults, often found in the spinal cord • Easier to remove when found in the spinal cord, difficult to remove from other locations  Ependymomas in the 4th ventricle/posterior fossa have a worse prognosis • Signs and symptoms are typical of hydrocephalus and elevated intracranial pressure if in the cranium  If spinal cord compression - paresis, pain, sensory deficits Meningiomas • Usually fairly benign tumors of adults  attached to the dura, often arise from the meningothelial cell of the arachnoid  compose about 20% of all primary brain tumours • Can be found:  along the external surfaces of the brain  within the ventricular system • Pathological findings:  Rounded masses with a dural base that compress underlying brain but are easily separated from it by a thin fibrous capsule  Sometimes extension into the overlying bone or “sheet-like” spreading through the brain can occur Meningiomas • Pathogenesis - FYI  Loss of the NF2 gene – regulates signaling through a variety of receptors that are involved in growth and the cell cycle • We’ll see it again in the disease neurofibromatosis • Clinical Features  Symptoms/signs of elevated intracranial pressure  Symptoms/signs caused by compression of • The cortex near the falx cerebri • Wing of the sphenoid • Foramen magnum  Interestingly, meningiomas tend to grow quite rapidly during pregnancy (not sure why) • Prognosis tends to be good – they tend to grow slowly and do not usually invade adjacent tissue  Surgery main treatment Medulloblastomas • A tumour with very poorly-differentiated, “primitive-looking” cells  Rapid growth, highly anaplastic  Can metastasize widely, and can even extend down into the cauda equina • Can occur in children or adults • Only grows in the cerebellum, and can obstruct CSF flow (due to encroachment on the 4th ventricle)  Signs and symptoms due to damage to the cerebellum and impaired drainage of CSF (hydrocephalus) • Has a good prognosis because it is very responsive to radiation therapy Brain metastases • Many tumours metastasize to the brain  The other tumours discussed so far are primary brain tumours – they started in the brain  Brain metastases are often found on/in the meninges but can also penetrate deep into cortical structures • Five most common primary (initial) sites that metastasize to the brain later include:  Lung  Breast  Melanoma (skin)  Kidney  GI tract cancers • Clinical features are the usual:  Elevated intracranial pressure findings  Focal findings from invasion and damage of specific brain structures • Most cancers have a relatively poor prognosis after brain metastases have occurred