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
Meningiomas clinical featres:
Symptoms/signs of elevated intracranial pressure
Symptoms/signs caused by compression of:
-cortex near the falx cerebri
-wing of the sphenoid
-Foramen magnum
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 is main treatment
Medulloblastomas:
A tumor 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 metastasis:
Many tumors metastasize to the brain:
-other brain tumors discussed, are primary brain tumors: 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
-Focal findings from invasion and damage of specific brain structures
Most cancers have a relatively poor prognosis after brain metastases have occurred.
