Neuropathology 2 - Brain Tumors PDF

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 Epidemiolog...

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: ▪ ▪ ▪ ▪ Grade I – pilocytic astrocytoma (commonly-used name) Grade II – diffuse astrocytoma Grade III – anaplastic astrocytoma Grade 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. 1297 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 astrocytoma Grade IV astrocytoma Necrotic, hemorrhagic infiltrating mass Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 28.45, p. 1294 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 ▪ 5-6 year median survival for Grade II, Grade II has a 10 – 20% 5-year 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 Disease 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, “primitivelooking” 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