Neuropathology II: Brain tumors Flashcards
Brain tumors 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 tumors tend to arise above the tentorium cerebelli in adults
Brain tumors; many seem relatively benign:
-grow slowly
-Relatively well-differentiated (minimal anaplasia)
Even a slow-growing, well-differentiated tumor in the brain can cause serious problems:
-Compression or destruction of smaller, critical brain areas such as the medulla
-Tumors 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 tumor or its removal
Aggressive, poorly differentiated brain tumors are among the deadliest of cancers
Astrocytomas:
Grades for astrocytomas range from I-IV:
higher grade tumors (ex 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;
pilocytic astrocytomas
-Tend to occur in children and young adults
-Often found in the cerebellum, optic nerves, 3rd ventricle
-Can be a solid or cystic mass: either way, the tumor 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 tyrosine kinases? like having a growth factor receptor constantly “turned on”
Grade II & III astrocytomas:
-More common in adults, usually found above the tentorium in the cerebrum (sometimes found in 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:
Glioblastoma multiforme
Unfortunately, the most common brain tumor 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
Astrocytomas clinical features:
Signs and symptoms:
-Headach (worse in morning) intesified by straining and coughing
-Nausea, vomiting
-6th crania nerve palsy
-Focal changes caused by invasion/damage of normal brain tissue (seizures, hemiparesis, ataxia, memory loss…
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 and treatment:
MRI the best imaging method
Treatment depends on the type of tumor:
-radiation
-chemotherapy
-Surgery
(all commonly used)
Signs and 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 tumors are common cases of brain herniations:
-Sub-falcine and transtentorial more likely w/ cerebral masses
Oligodendrogliomas:
5%-15% of gliomas (most common in 40’s & 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 slow 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 can also produce lots of CSF, therefore, can cause communicating (excess of CSF) or non-communicationg (blackage 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 int he 4th ventricle/posterior fossa have the worst 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 tumors
Can be found:
-along the external surfaces of the brain
-within the ventricular system
Pathological findings:
-Rounded masses w/ 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
