Nervous System Malignancies Flashcards
3 characteristics of neoplasms
*autonomous - growth is independent of physiologic growth signals
*clonal - acquired mutations affect cell and its progeny
*proliferative - mutations confer cell survival and growth advantage
benign vs. malignant neoplasms
*differentiation - how well do neoplastic cells resemble normal?
*invasion - is there infiltration/destruction of surrounding tissues?
*metastasis - has neoplasm spread to physically discontinuous sites?
behavior of neuro neoplasms
*benign vs. malignant distinction less evident in the brain:
-confined space in skull
-widely infiltrate the brain parenchyma
-may be lethal if situated in critical brain region, even if “benign”
*patterns of spread differs from other organ systems
-may spread within CNS through the CSF
-rarely metastasize to other organ systems
primary neuro neoplasms
*from cells intrinsic to the nervous system
*locally infiltrative and destructive
*approx 66% of neuro neoplasms
metastatic neuro neoplasms
*from other organ systems (LUNG, breast, kidney, skin)
*multiple, well-circumscribed lesions at gray-white matter junction
*approx 33% of neuro neoplasms
typical adult neuro neoplasms
*SUPRAtentorial/cerebral hemispheres
*types: glioblastoma, meningioma, schwannoma
typical childhood neuro neoplasms
*INFRAtentorial/posterior fossa
*account for nearly 20% of all cancers in childhood
*types: pilocytic astrocytoma, ependymoma, medulloblastoma
risk factors of neuro neoplasms
*most CNS tumors are sporadic
*about 1% are hereditary
*immunosuppression - strongly associated with primary CNS lymphoma
*RADIATION is a strong risk factor, esp for gliomas and meningiomas
neurofibromatosis type 1
*inherited neoplastic syndrome
*gene = NF1 (17q11)
*tumor types = neurofibroma, pilocytic astrocytoma
neurofibromatosis type 2
*inherited neoplastic syndrome
*gene = NF2 (22q12)
*tumor types = schwannoma, meningioma, ependymoma
tuberous sclerosis
*inherited neoplastic syndrome
*gene = TSC1/TSC2 (9q34/16p13)
*tumor types = subependymal giant cell astrocytoma
Von Hippel-Lindau
*inherited neoplastic syndrome
*gene = VHL (3p25)
*tumor type = hemangioblastoma
Li-Fraumeni
*inherited neoplastic syndrome
*gene = TP53 (17p13)
*tumor types = gliomas
primary neuro neoplasms - classification
*glial tumors/gliomas (astrocytomas, oligodendrogliomas, ependymomas)
*embryonal tumors (medulloblastomas)
*meningiomas
*nerve sheath tumors (schwannomas)
what types of things cause ring-enhancing lesions on MRI of brain
*high-grade gliomas (ex. glioblastomas)
*abscesses
*central nervous system toxoplasmosis
*organizing infarcts
gliomas - overview
*neoplasms of glial cell origin (non-specific)
*types: astrocytomas, oligodendrogliomas, ependymomas
*tissue biopsy required to confirm dx
gliomas - general characteristics
-no recognizable premalignant or in situ stages
-produce major clinical abnormalities
-rarely spread outside CNS
gliomas - signs and symptoms
*focal OR generalized signs/symptoms:
-headaches, seizures, aphasia, vomiting, visual disturbances
-cognitive dysfunction (memory + mood disorders)
-intracranial pressure may be increased
-suspected on basis of imaging studies (MRI)
grade I glioma
*slow growing and unlikely to spread
*survival > 5 years; curable if excised
*general category = benign (pilocytic astrocytoma)
grade II glioma
*unlikely to grow and spread, but more likely to come back after treatment
*survival > 5 years; tendency to recur
*general category = low grade malignant (oligodendroglioma, diffuse astrocytoma)
grade III glioma
*grow quickly with rapidly dividing cells, but no necrosis
*survival 2-3 years
*general category = high grade malignant (anaplastic astrocytoma)
grade IV glioma
*grow and spread quickly with rapidly dividing cells; has vascular proliferation and necrosis
*survival < 1 year
*general category = high grade malignant (glioblastoma)
astrocytoma - pathogenesis
*mutation of IDH1 (or IDH2)
*mutated genes encode forms of isocitrate dehydrogenase with new enzymatic activity
*presence of IDH1/2 mutations predicts better prognosis in all grades of astrocytic tumors
astrocytomas - overview
*neoplasms of astrocytes
*specific type of glioma
classifications of astrocytomas
*non-infiltrative/localized: pilocytic astrocytoma (grade I)
*infiltrative:
-diffuse astrocytoma (grade II)
-anaplastic astrocytoma (grade III)
-glioblastoma (grade IV)
pilocytic astrocytoma - overview
*BENIGN neoplasm of astrocytes (grade I); non-infiltrative
-most common benign CNS tumor in children
-very slow growing, usually arises in cerebellum
pilocytic astrocytoma - pathogenesis
*mutations/translocations involving BRAF (functions in RAS signaling pathway)
*IDH1 mutations NOT seen
pilocytic astrocytoma - appearance
*discrete CYSTIC lesion with mural nodules
*biphasic architecture: loose “microcystic” and compact, densely fibrillar areas
*ROSENTHAL FIBERS: bright-red corkscrew-shaped astrocyte inclusion
infiltrative astrocytomas - overview
*MALIGNANT neoplasms of astrocytes (grade II-IV)
*account for 80% of adult gliomas, usually in the 40s-60s
*low-grade tumors progress to high-grade tumors
*on imaging, low grade is non-enhancing, and high-grade is enhancing
diffuse astrocytoma
*grade II (infiltrative) astrocytoma
*most common in young adults
*IDH1 mutations
*transition between neoplastic and normal tissues not distinct:
-infiltrate diffusely
-increased cellular astrocyte proliferation with atypia
-mitoses RARE
-microvascular proliferation + necrosis ABSENT
anaplastic astrocytoma
*grade III (infiltrative) astrocytoma
*IDH1 mutations
*transition between neoplastic and normal tissues not distinct:
-mitoses increased
-microvascular proliferation
-necrosis ABSENT
glioblastoma
*grade IV (infiltrative) astrocytoma
*most common and most malignant primary brain tumor of adults (commonly crosses corpus callosum - “butterfly” lesion)
*NOT associated with IDH1, unless progression from lower grade
*transition between neoplastic and normal tissues not distinct:
-highly pleomorphic
-mitoses numerous
-extensive endothelial proliferation and areas of necrosis
oligodendrogliomas
*malignant neoplasm of oligodendrocytes
*constitute 5-15% of gliomas
*best prognosis among glial tumors (survival of 10-20 years, depending on grading)
oligodendrogliomas - gene defect
*IDH1/2 mutation
AND
*deletion of 1p and 19q
oligodendrogliomas - clinical features
patients may have had several years of neurologic complaints, often including seizures
oligodendrogliomas - gross features
*usually frontal lobe
*predilection for white matter
*gelatinous, gray masses, often cystic, focal hemorrhages, and calcifications
oligodendrogliomas - histological features
*regular cells with spherical nuclei
*clear halo cytoplasm, “fried eggs”
*grade II = low mitotic activity
*grade III = anaplastic, higher cell density, anaplasia, increased mitoses, necrosis
ependymomas - overview
*malignant neoplasm of ependymal cells
*10% of pediatric brain tumors (typically posterior fossa)
*in adults, typically spinal cord (22q deletion ; NF2 gene mutation)
ependymomas - clinical features
*posterior fossa -> non communicating hydrocephalus (progressive obstruction of 4th ventricle)
*CSF dissemination uncommon
ependymomas - pathology
*cells with fibrillary processes contain regular nuclei
*canals = glandlike elongated structures with lumen (resembling embryologic ependymal canal)
*pseudorosettes = perivascular nuclear-free zones
embryonal tumor (medulloblastoma) - overview
*malignant neoplasm of cerebellar stem cells
*accounts for almost 20% of pediatric tumors
*most tumors located cerebellum midline
*molecular groups vary in terms of age of onset, tumor location, and prognosis
embryonal tumor (medulloblastoma) - clinical features
*posterior fossa -> non communicating hydrocephalus (progressive obstruction of 4th ventricle)
*CSF dissemination: meningeal “icing” or spinal “drop mets”
*highly malignant; however, exquisitely radiosensitive
embryonal tumor (medulloblastoma) - pathology
*densely cellular, undifferentiated small blue cells (embryonal)
*Homer-Wright rosettes surrounding central neuropil
meningioma - overview
*predominantly benign neoplasms of arachnoid meningothelial cells
*found along any of the external surfaces of the brain (usually attached to dura)
*most common benign CNS tumor in adults (rare in children)
meningioma - pathogenesis
*loss of long arm chromosome 22 (22q deletion)
-including NF2 gene, which encodes the protein merlin
-about 50% of sporadic meningiomas have loss-of-function mutations of NF2
*increased risk with prior radiation therapy to head/neck
meningioma - clinical features
*slow-growing, solitary tumors
*vague non-localizing, or focal referable symptoms to adjacent brain compression
*may express variety of hormones (grow rapidly during pregnancy)
meningioma - gross features
*round mass attached to dura (may compress underlying brain)
*common sites:
-parasagittal convexity
-lateral convexity
-sphenoid wing, olfactory groove, sella turcica
meningioma - histologic features
*push, rather than infiltrate
*compact clusters/whorls of cells
*psammomatous calcifications
*malignant variants = high grade)
CNS metastatic disease
*metastatic meningeal or parenchymal brain lesions
*account for 25-50% of intracranial tumors
CNS metastatic disease - clinical features
*may be first manifestation of systemic disease
*present as mass lesions: may be multiple; meningeal carcinomatosis
*common primary sites = LUNG, breast, skin, kidney, GI
CNS metastatic disease - pathology
*intraparenchymal sharply demarcated masses (usually at gray-white matter junction)
*typically resemble parent tumor type (phenotyping helpful for identifying the primary neoplastic site)
schwannoma - overview
*benign neoplasm of Schwann cells
*nerve sheath tumors
*arise directly from peripheral or cranial nerves (may arise within dura)
*inactivating mutations of NF2 gene on chromosome 22
schwannoma - clinical features
*local compression of involved nerve or adjacent structures
*dural: acoustic neuroma (attached VIII: vestibular branch; present with tinnitus and hearing loss)
*extradural
*surgical removal is curative
schwannoma - gross features
*well-circumscribed, firm gray encapsulated masses
*attached loosely to associated nerve without invading
*lesion displaces nerve of origin as it grows
*can often be resected without sacrificing nerve function
schwannoma - histologic features
*Schwann cells with spindled/wavy, elongated nuclei
*a mixture of dense and loose zones:
-Antoni A = dense cellular areas
-Antoni B = loose cellular areas
