B120 Tumors of the CNS and PNS Flashcards
General CNS tumor characteristics
50‐75% are primary tumors, and the rest are metastatic.
CNS tumors a large proportion of cancers of childhood, up to 20% of all tumors.
- CNS tumors in childhood differ from those in adults both in histologic subtype and location.
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childhood, tumors are likely to arise in the posterior fossa
- Most common in children are pilocytic astrocytoma, ependymoma, and meduloblastoma,
- adults they are mostly supratentorial
Malginant vs. Benign tumor distinction is not clear for most tumors, and the prognosis is much more dependent on the site of the tumor, what adjacent structures it may damage, and its operability.
Also, CNS tumors very rarely metastasize elsewhere, with the only exception being into the subarachnoid space for seeding to other spots within the CNS.
Types of CNS tumors. list
7 categories, 11 total
- Gliomas: most frequent adult tumor, 80%
- Astrocytomas
- Oligodendrogliomas
- Ependymoma
- Neuronal tumors:
- Central neurocytoma
- Gangliogangliomas
- Dysembroplastic Neuropithelial tumor
- Neuroectodermal tumors aka poorly differentiated tumor
- Medulloblastoma
- Meningiomas
- Primary CNS lymphomas
- Germ cell tumor
- Metastatic tumors
Diffuse Astrocytomas
General: very infiltrative, cytologically resemble glial cells (marker expression), have diffuse, invasive borders.
Astrocytomas:
Diffuse astrocytoma:
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Presentation
- Develop in the cerebral hemispheres
- Appears in the 30’s thru 50’s
- The main variant, 80% of adult gliomas (and astrocytomas are 80% of all adult CNS tumors)
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Morphology
- gray/white, infiltrative tumors, expand the tissue without forming a discrete mass.
- infiltration has always occured beyond visible margins.
- cut surface can be firm or soft
- cystic degeneration/necrosis is possible but not a major feature
- in advanced glioblastoma there is high variability in the tumor regions on gross appearance, with more yellow necrotic areas and areas of hemorrhage
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Histology: 3 groups, which define the grade of the tumor.
-
Well differentiated - grade 2
- moderate increase glial cell nuclei mitoses
- mild but low anaplasia
- mild increase in astrocyte cell density
- background stroma of astrocyte GFAP staining processes.
- border of tumor is indistinguishable as it merges with normal CNS, and can extend for several centimeters beyond apparent border.
-
anaplastic - grade 3
- more densely cellular
- more pleomorphism and mitotic figures
-
glioblastoma - grade 4
- Previously called glioblastoma multiforme
- Similar to anaplastic form, but
- with areas of necrosis and often pseudopalisading nuclei
- or vascular proliferation.
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Well differentiated - grade 2
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Symptoms
- __focal neuro deficits, site related
- Seizures
- Headaches
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Progression
- Well differentiated astrocytoma can remain for several years, but it inevitably progresses through the more advanced stages
- Mean survival is more than 5 years, 6-8 years.
- Some patients present immediately with anaplastic or glioblastoma. Once glioblastoma manifests, mean survival is 15 months, with aggressive treatment.
- Mutations:
- p53 and RB loss of functions
- PI3-kinase gain of function mutations
- Isocitrate Dehydrogenase 1 and 2 IDH1 and IDH2 are very common in low grade astrocytomas and are used for staining to check biopsies.
Pilocytic astrocytoma
Relatively benign tumors, affect children and young adults.
Morphology
- Appear in the cerebellum and sometimes, third ventricle/hypothalamus, optic tract and chiasm, and spinal cord. Uncommonly may appear in the cerebral hemispheres.
- Usually causes formation of a cyst, and cyst growth causes more problems than the tumor growth.
- The tumor itself is visible as a mass located on one side or paritally/totally encricling the cyst.
- It is difficult to resect, and incomplete resection again results in formation and growth of the cyst.
Histology:
- formed of ‘pilocyte’ astrocytes
- mat/meshlike tumor of astrocytes with small cell bodies and long thing bipolar or tripolar major processes. GFAP positive.
- there is little to no mitotic figures or necrosis.
- Rosenthal fibers: elongated, worm-like or “corkscrew” eosinophilic (pink) bundle that is found on H&E staining of the brain in the presence of long-standing gliosis. Formed by aggregates of intermediate filaments, including GFAP.
Mutations:
- High percentage have BRAF activating mutations (ser/thr kinase), (as do melanomas, and the specific V600E mutation seen in all hairy cell leukemia)
- IDH1 and IDH2 mutations are not seen and this is a major distinguishing factor between pilocytoma and low grade astrocytoma.
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Ependymoma
originate from ependymal cell lining the ventricles.
Typically seen in children where it arises in the 4th ventricle, and may present with non-communicating hydrocephalus are 5-10% of all primary brain tumors in children.
In adults it arises around the spinal central canal. and is associated with inherited mutations to the NF1 gene as part of neurofibromatosis syndrome. (its own card).
5 year survival is 60%, for children. Prognosis is better for cerebral or spinal tumors, and worse for subtentorial tumors.
Since they stick into the ventricles, they commonly disseminate via the CSF.
They can typically be treated by surgery.
Histology:
- Hallmark is formation of rosettes around elongated thin, irregularly shaped canals and pseudorosettes around vasculature
- It is typically well differentiated
- Stains for GFAP in the ependymal processes
- May present as myxopapillary ependymoma, with papillae that have a myxoid core, lined by the neoplastic ependymal cells.
- Anaplastic ependymomas are more dense, more mitotic and necrotic, and have a worse prognosis
Central neurocytoma
A low grade tumor found adjacent to the ventricles.
Formed by evenly spaced, round, uniform nuclei and islands of neuropil.
Gangio-gangliomas
Mixtures of neoplastic cells that are both glial and well differentiated neuronal cells.
Slow growing tumors, but the glial component has a risk to transform to anaplastic glioblastoma type.
Frequently present with seizures.
Dysembryoplastic neuroepithelial tumor
Distinct childhood tumor.
Slow growing, with a relatively good prognosis after resection.
Often presents as seizures.
Usually located in the superficial temporal lobe.
Small, round neuronal cells arranged in columns, around a central core of processes reminscent of cells growing around a radial glial process. - think neuroepithelial (also like the ependymoma is in childhood), and its like a dysregulation of a normal embryologic process, so dysembryoplastic, neuroepithelial tumor.
Form discrete intracortical nodules with a myxoid background.
There are also well differentiated neurons floating within the myxoid fluid/stroma.
Oligodendroglioma
Presentation and prognosis
- Arising from oligodendrocytes, 5-15% of gliomas
- Most commonly in the 30’s and 40’s
- Preceeded by several years of neurologic omplaints, such as seizures
- Appear in the cerebral hemispheres, white matter
- Has a better prognosis than astrocytomas, but is still aggressive
- Mean survival is 5-10 years, with surgery, chemo, and radiation therapy.
Morphology:
- Gelatinous, soft, gray mass
- May have cysts, hemorrhage, and calcifications
- irregular borders, non-distinct
- Calcification is a prominent feature, and occurs in 90%. Can be microscopic foci or massive depositions in the tumor.
Histology
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Low grade oligodendroglioma:
- Distinctive cells with large, rounded, pleomorphic nuclei, but with normal looking chromatin, fine, granular, and a very large perinuclear cytoplasmic halo.
- Tumors are usually highly vascular with a meshwork anastomosing capillaries.
- Very few mitotic figures
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High grade, anaplastic oligodendroglioma__
- increased cell density, anaplasia, and mitotic figures.
- more aggressive and worse prognosis.
Medulloblastoma
Predominantly in children, and exclusively originating in the cerebellum.
It has the characteristic appearance of other primitive tumors, called a “small round cell” tumor, little stroma and no other cell types.
Both neuronal and glial markers are expressed, and differentiation of cells may occur down either route.
It is very malignant, and if untreated the prognosis is horrible, but, it is highly radiosensitive. Treatment wit hexcision, chemo, and irradiation, the 5yrS is 75%.
A similar type of tumor can arrise in other parts of the nervous system as PNETs, arising from neuroectoderm, in male children as bone tumors.
In children usually cerebellar midline, and in adults laterally.
Primary Central nervous system lymphoma
Primary CNS lymphoma, occurring mostly as diffuse large
B cell lymphomas, accounts for 2% of extranodal lymphomas
and 1% of intracranial tumors. It is the most common
CNS neoplasm in immunosuppressed persons
Caused by oncogenic EBV infection of the lymphocytes.
Primary brain lymphoma is aggressive, with poor response to chemo and a bad prognosis.
These tumors still rarely metastasize out of the brain.
Germ Cell Tumors
Primary brain germ cell tumors occur along the midline,
most commonly in the pineal and the suprasellar regions
They account for 0.2% to 1% of brain tumors in people of
European descent but as many as 10% of brain tumors in
persons of Japanese ethnicity. They are a tumor of the
young, with 90% occurring during the first 2 decades of
life. Germ cell tumors in the pineal region show a strong
male predominance.
CNS germ
cell tumor is germinoma, a tumor that closely resembles
testicular seminoma
Meningiomas, general characteristics
- Typically benign
- Typically in adults
- arise from arachnoid meningeal epithelial cells.
- can arise on any brain surface or within the ventricules, from stromal arachnoid cells of the choroid plexus
- Sypmtoms appear from compression of local brain structures or occlusion of CSF pathways and hydrocephalus.
- They are usually easily resectable, uncommonly they may infiltrate the brain tissue and this has a high risk for recurrence.
- Multiple meningiomas are associated with Neurofibromatosis type 2, and have a mutation to the NF2 tumor suppressor gene.
Meningioma types and grading
Histological types:
Syncytial: Whorled clusters of cells without visible membranes, forming a syncytium. in tight clusters.
Fibroblastic: spindle cells and abundant collagen
Transitional: features both types of cells
PSammomatous: with a whole buncha psamommas
Secretory: With PAS positive eosinophilic secretions forming extracellular deposits, called pseudopsammoma bodies.
Grading: Meningioma –> atypical meingioma –> anaplastic meningioma
fortunately, these are generally the normal type meningiomas, and anaplastic meningioma is rare, less than 1% of all meningiomas.
Atypical;
- more prominent nucleoli
- increased cell density
- more mitoses
- loss of typical subtype patterns.
Anaplastic;
- highly aggressive, may resemble high grade either high grade sarcoma or carcinoma, with histologic evidence of meningothelial origin.
Low grade: Well defined mass, with no extension to the brain. Bone extension may be present.
Von Hippel Lindau disease
Autosomal dominant disorder of:
- Hemangioblastomas, mainly in the: cerebellum and retina, and also, brain stem, spinal cord, and nerve roots.
- Hemangioblastomas are composed of endothelial cells, pericytes and stromal cells.
- Cyst formation in the pancreas, liver, and kidneys, and an increased risk for Renal Cell Carcinoma
- Are also at risk for paraneoplastic polycytemia, from VEGF driving EPO production.
Morphology
- Within the cerebellum it forms as a highly vascular neoplastic nodule, that induces a large cyst, which the tumor sits on the border of.
Histology
- capillary sized thin walled vessels, and stromal cells with vacuolated lipid rich cytoplasm.
Pathogenesis:
- Mutated VHL tumor suppressor gene.
- VHL is a ubiquitin ligase that degrades Hypoxia inducible factor.
- HIF drives expression of VEGF
- Increased VEGF, increased risk for Hemangiomas (and renal cell carcinoma)
