Pathology of Brain Tumors Flashcards
Primary brain tumors
Where do they come from
Tumors of neuroectodermal cells
Mesenchmyal/neural crest cells
Tumors arising in the sellar region
Tumors of non-neuroectodermal origin
Primary brain tumors
Tumors of neuroectodermal cells
list
gliomas: tumors resembling of differentiated brain cells (astrocytomas,oligodendrogliomas, ependymomas, glioblastoma multiforme, choroid plexus tumor, others)
primitive neuroectodermal tumors (PNET): tumors resembling embryonic brain cells (medulloblastoma, cerebral PNET, others)
Primary brain tumors
Mesenchymal/neural crest tumors
list
tumors of brain coverings (meningiomas, others) tumors of nerve roots and peripheral nerves, usually Schwann cells (Schwannomas and neurofibromas, others)
Primary brain tumors
Mesenchymal/neural crest tumors
Tumors arising in the sellar region
tumors derived from Rathke’s pouch (pituitary adenomas, craniopharyngioma)
Primary brain tumors
Mesenchymal/neural crest tumors
Tumors of non-neuroectodermal origin
primary CNS lymphomas, germ cell tumors, etc.
Secondary tumors of the brain
list
intraparenchymal or meningeal metastases (carcinomas, melanomas, systemic lymphomas, etc.)
Brain tumors
Why do they produce clinical sx
Most brain tumors produce clinical symptoms because of mass effect (increased ICP, headache, papilledema), local damage to particular brain structures (focal neurologic deficits), or seizures (usually from damage to cerebral cortex).
Primary brain tumors
Benign or malignant
Primary CNS tumors rarely metastasize outside the CNS and then usually only after surgical biopsy or resection, presumably due to disruption of normal anatomic barriers.
Some tumors (e.g., some gliomas, medulloblastoma), however, can disseminate within CSF pathways causing damage to cranial and spinal nerve roots, blockage of CSF flow with hydrocephalus, etc., despite being relatively low-grade under the microscope.
Prognosis is frequently more related to location and resectability than to histologic type or grade of tumor: e.g., pilocytic astrocytoma (WHO grade 1) located in the optic nerve or hypothalamus may be devastating but in the cerebellum amenable to curative resection.
Primary brain tumors
classification
The terms “benign” and “malignant” are, thus, best avoided, except for certain primary tumors (e.g., primary CNS lymphoma) and metastases to the brain, which are, by definition, malignant. Tumors are, however, graded based on their histologic appearance: low grade = WHO grades 1-2 (usually implies relatively good long-term prognosis); high grade = WHO grades 3-4 (indicates likelihood of rapid growth and poor long-term prognosis). Staging criteria exist but are less utilized than for tumors in other organs.
Gliomas
Types
list
Astrocytomas
Oligodendroglioma
Ependymomas
Choroid plexus tumors
Most common primary brain tumor
Astrocytoma
Diffuse astrocytoma
Gen chars
these characteristically infiltrate the brain (cerebrum in adults, brainstem in children) and show a spectrum of anaplasia with a correspondingly aggressive clinical course.
astrocytoma (WHO grade 2) anaplastic astrocytoma (WHO grade 3)
glioblastoma (AKA glioblastoma multiforme) (WHO grade 4).
Diffuse astrocytoma
Grade vs age
Lower-grade tumors tend to occur in younger to middle-aged adults, and older adults generally have higher-grade tumors at initial diagnosis.
Diffuse astrocytoma
Glioblastoma
Char features
The highest-grade tumor (glioblastoma) typically shows areas of proliferation of microvessels (producing contrast enhancement on imaging studies) and necrosis.
Diffuse astrocytoma
Median survival
Median survivals from diagnosis approximate 5 years for astrocytoma, 2 years for anaplastic astrocytoma, and less than 1 year for glioblastoma. When tumors recur, they have often progressed to a higher grade with correspondingly shortened survival.
Pilocytic astrocytoma
Gen chars
Pilocytic astrocytoma (WHO grade 1): characteristically occurs in children or young adults, usually in the cerebellum, optic nerve, or spinal cord, and usually has an indolent course. Formation of macroscopic cysts and microscopic accumulations of alphaBcrystallin protein in tumor cells (Rosenthal fibers) are common. Tumors only rarely progress to a higher grade at recurrence.
Oligodendroglioma
chars
Oligodendroglioma (WHO grade 2) and anaplastic oligodendroglioma (WHO grade 3): these usually occur in the cerebrum of younger adults, show infiltrative growth, often cause seizures, and may contain calcifications. Median survival approaches 10 years for grade 2 tumors
Ependymomas
chars
Ependymomas (grade 1 or grade 2) grow as solid tumors, typically in the ventricles or central canal of the spinal cord, may cause obstructive hydrocephalus, and may form microscopic structures resembling mini- ventricles (true ependymal rosettes). Anaplastic ependymoma (grade 3) usually occurs in children. Prognosis varies by subtype and grade, but ependymomas in children often have poor long-term outcomes.
Choroid plexus tumors
Gen chars
Choroid plexus tumors (choroid plexus papilloma, WHO grade 1, or choroid plexus carcinoma, WHO grade 3) also occur within the ventricles and may cause obstructive hydrocephalus or overproduction of CSF.
Primitive neuroectodermal tumors (PNET)
Gen chars
Tumors resembling embryonic brain cells most commonly occur in children, are highly aggressive tumors, and may occur in the setting of particular tumor syndromes.
PNET
Most common type
Medulloblastoma
Medulloblastoma
Gen chars
Medulloblastoma (WHO grade 4): is the most common PNET, occurs in the cerebellum, often shows primitive neuronal differentiation (sometimes in the form of microscopic structures called Homer-Wright rosettes), and has a tendency to disseminate in the subarachnoid space or even outside the CNS. Although many medulloblastomas can be successfully treated, bad prognostic signs include deletion of chromosome 17p, MYC amplification, and inability to achieve a complete resection at initial treatment
PNET
Medulloblastoma-like tumors in other CNS sites
Medulloblastoma-like tumors occur in other CNS sites and are termed simply CNS PNET. These are genetically distinct from medulloblastoma and have a worse prognosis. Similar tumors can also arise primarily in the peripheral nerves and are termed “peripheral PNET.” These appear to be cytogenetically different from central PNET.
Meningeal Tumors
Where do they come from
Most tumors arising in the subarachnoid space are derived from the arachnoidal cells and are called meningiomas.
Meningiomas
Who do they occur in/why do they cause sx
Meningiomas are typically solid tumors, occur in older adults, and produce symptoms by compressing the underlying brain or spinal cord and by causing increased intracranial pressure.
Meningiomas
Assoc with…
Many are associated with deletions in chromosome 22. Meningiomas may also occur as a second tumor following radiation therapy.
Meningiomas
Subtypes/classic feature
meningiomas come in a variety of subtypes; most are grade 1, but grade 2 (atypical meningioma) and grade 3 (anaplastic meningioma) also occur. The higher grades grow more rapidly and show a higher incidence of recurrence following resection, but infrequently metastasize.
calcifications known as psammoma bodies are common.
estrogen hormones may play a role in pathogenesis and account for a higher incidence in women.
Tumors of non-neuroectodermal origin
Primary CNS lymphoma
Chars/type
Although the CNS does not contain lymphatics or lymphoid tissue, primary lymphomas occasionally arise as CNS intraparenchymal tumors. These are most commonly high-grade large B cell lymphomas.
Tumors of non-neuroectodermal origin
Primary CNS lymphoma
Most common in…/how to dx
They are most common in elderly or immunosuppressed people. Individuals with AIDS are at particular risk, and AIDS-associated lymphomas have a strong association with Epstein-Barr virus infection.
Primary or metastatic lymphomas in the CNS may display solid or infiltrative growth patterns and, hence, be difficult to diagnose clinically or by imaging.
Primary CNS germ cell tumors
Gen chars
Tumors of germ cells (teratoma, dysgerminoma, choriocarcinoma, etc.) are most commonly found in the gonads but can occasionally arise in the CNS, usually in the pineal or the hypothalamus of children and young adults. Other than teratomas, germ cell tumors are malignant and produce effects by rapid growth and compression or destruction of surrounding structures (e.g., hypothalamus). Measurement of markers such as α-fetoprotein and β-HCG can aid in diagnosis.
Metastatic tumors
Patterns of involvement
20-30% or more of brain tumors are metastatic, depending on series: incidence is greater in older people (paralleling increased incidence of cancer). Patterns of involvement include:
intraparenchymal masses
leptomeningeal masses and diffuse dissemination (leptomeningeal carcinomatosis)
craniospinal masses +/- fractures
paraneoplastic syndromes (covered in another lecture)
Metastatic tumors
sources
Sources (approximate order of frequency): lung, breast, malignant melanoma, kidney, GI tract, others, including systemic lymphomas.
Metastatic tumors
Clinical manifestations
Clinical manifestations include mass effect, seizures, focal deficits, and stroke-like syndromes (due to hemorrhage) but many may be asymptomatic. 85% or more are multiple within nervous system.
May occur in patients with advanced systemic cancer or be the first manifestation of systemic cancer.
Metastatic tumors
pathology
Usually solid or cystic, circumscribed mass, often with central necrosis; often cause prominent vasogenic edema in surrounding brain.
Leptomeningeal carcinomatosis (“carcinomatous meningitis”)
Diagnostic findings/can clinically mimick
Spread of tumor cells into the subarachnoid spaces and through the CSF pathways is often associated with high CSF protein, hydrocephalus, and involvement of multiple cranial and spinal nerve roots, clinically mimicking an acute or chronic leptomeningitis.
Leptomeningeal carcinomatosis (“carcinomatous meningitis”)
Clinical findings
Leptomeningeal carcinomatosis (LC) may be asymptomatic, produce non-specific symptoms such as malaise and headache, or cause complex patterns of deficit, making clinical diagnosis difficult. A high index of suspicion supplemented by detailed neuroimaging and study of CSF may help.
Leptomeningeal carcinomatosis (“carcinomatous meningitis”)
Occurs most frequently with…
LC occurs most frequently with breast carcinoma, lung carcinoma, small cell carcinoma, systemic lymphoma, and medulloblastoma.
Who is likely to have a genetic syndrome predisposing to brain tumor
Although most brain tumors are not associated with identifiable genetic syndromes, a number of genetic syndromes, such as neurofibromatosis (NF), are associated with occurrence of tumors involving the nervous system as well as other organs. Patients with both CNS and other tumors or with multiple tumors in the brain or other organs are likely to have a genetic syndrome predisposing to tumor formation.
CNS/PNS tumors/Typical non-neural tumors
NF-1
CNS/PNS Tumors: Nerve sheath tumors, Gliomas
Typical non-neural tumors: hamartomas
CNS/PNS tumors/Typical non-neural tumors
NF-2
CNS/PNS Tumors: Nerve sheath tumors, Gliomas, Meningiomas
Typical non-neural tumors: pheochromocytomas
CNS/PNS tumors/Typical non-neural tumors
Tuberous sclerosis
CNS/PNS Tumors: Special forms of astrocytoma
Typical non-neural tumors:Renal tumors
CNS/PNS tumors/Typical non-neural tumors
VHL
CNS/PNS Tumors: Hemangioblastoma
Typical non-neural tumors:Renal Cell CA
CNS/PNS tumors/Typical non-neural tumors
Ataxia-Telangiectasia
CNS/PNS Tumors: Gliomas
Typical non-neural tumors:
Leukemia
Lymphoma
Telangiectasia
CNS/PNS tumors/Typical non-neural tumors
Turcot
CNS/PNS Tumors: Medulloblastoma
Typical non-neural tumors: Adenomatous polyp
CNS/PNS tumors/Typical non-neural tumors
Gorlin
CNS/PNS Tumors:
Medulloblastoma
Meningioma
Typical non-neural tumors:
Skin based cell CA
CNS/PNS tumors/Typical non-neural tumors
Li-Fraumeni
CNS/PNS Tumors:
Glioma
Medulloblastoma
CP Papilloma
Typical non-neural tumors:
Breast/colon CA
Brain tumors in adults
Cerebrum
list
astrocytomas/glioblastomas metastatic carcinomas meningiomas oligodendrogliomas lymphomas pituitary adenomas
Brain tumors in adults
Posterior fossa
list
metastatic carcinomas
meningiomas
Schwannomas (CN VIII)
Brain tumors in children
Cerebrum
list
PNET’s (cerebral PNET) ependymomas choroid plexus tumors optic nerve gliomas germ cell tumors craniopharyngiomas
Brain tumors in children
Posterior fossa
list
PNET’s (cerebellar medulloblastoma)
pilocytic astrocytomas
ependymomas
brainstem gliomas
