P- Tumors of the Nervous System Flashcards
What factor has an association with development of intracranial tumors?
- high dose/therapeutic doses of X-irradiation
There is no firm association with:
- environmental carcinogens
- smoking
- virus
- trauma
- low dose, long term irradiation [x-ray or in nuclear plants]
What are the 4 major familial tumor syndromes for nervous system tumors?
- NF1
- NF2
- VHL syndrome
- tuberous sclerosis
Where is a tumor likely to be if there are:
- motor symptoms
- dementia/alheimers
- increased intracranial pressure
- motor cortex or corticospinal tract
- frontal cortex
- pineal region, region of 3rd ventricle or vermis of cerebellum
What is the most likely cell of origin for brain neoplasms?
multipotential stem cells that reside in developing and mature tissue
What factors of nervous system tumors allow for diagnosis and prognosis?
- type of differentiation
2. grade of the neoplastic cells
Where do most intracranial tumors occur in patients over 50 years old?
What are the most common types?
above the tentorium in the cerebrum
High-grade:
- diffusely-infiltrating astrocytomas
- meningiomas
- metastatic carcinomas
- Oligodendrogliomas
Where do the majority of CNS tumors in childhood occur?
What are the most common types?
What is the WHO grade for each type?
Posterior fossa [brainstem and cerebellum]
- pilocytic astrocytoma - 1
- ependymomas- 2,3
- medulloblastomas -4
What are the main primary intradural tumors?
- meningioma
- schwannoma
- neurofibroma
What cells make up meningiomas?
How fast do they grow and how well differentiated are they?
incompletely differentiated meningothelial cells
[external layer of arachnoid]
Slow growing
low grade [epithelioid cells with low N:C ratio]
WHO 1,2,3
What patients are likely to have multiple menigiomas?
Patients with NF2
What age and sex is more affected by meningiomas?
50-70
Women
Where in the CNS are meningiomas most likely to form?
- over cerebral convexities
other locations: base of cerebrum at sphenoid ridges and olfactory grooves
A 50 year old woman come in complaining of headache.
You do a CT and note a well-circumscribed mass attached to the dura. It shows contrast enhancement.
You take a gross section and note a firm, rubbery, lobulated mass.
On histological section you see:
- epithelioid cells that are round/oval with abundant cytoplasm that appear to wind in spiral whorls
- psammoma bodies in the whorl
What type of tumor are you suspicious of?
Meningioma- meningothelial subtype
A 50 year old woman come in complaining of headache.
You do a CT and note a well-circumscribed mass attached to the dura. It shows contrast enhancement.
You take a gross section and note a firm, rubbery, lobulated mass.
On histological section you see:
- elongated cells that appear eliptical with a collagenous ECM that appear to wind in spiral whorls
- psammoma bodies in the whorls
What type of tumor are you suspicious of?
Meningioma - fibroblastic subtype
A 50 year old woman come in complaining of headache.
You do a CT and note a well-circumscribed mass attached to the dura. It shows contrast enhancement.
You take a gross section and note a firm, rubbery, lobulated mass.
On histological section you see:
- epithelioid cells that are round/oval with abundant cytoplasm.
- elongated spindle cells
- whorls with psammoma bodies
What type of tumor are you suspicious of?
Meningioma- transitional variant
What is the most common cytogenetic abnormality in meningiomas?
- Loss of chromosome 22
- NF2 gene mutation in 60% of tumors
What is the prognosis for meningiomas?
Most are WHO grade 1 meaning that they are space expanding masses that do not infiltrate surrounding tissue.
1 = recurrence below 25%
2 = recurrence below 50%
3 = recurrence 50-94%
What type of cell makes a diffusely infiltrating astrocytoma?
What WHO grade are they?
What age is most affected?
It is made of incompletely differentiated glial cells that exhibit partial astrocytic differentiation
-most occur in the cerebrum
WHO 2
It mostly affects people between 20-45 [60%
A 26 year old man comes into the office complaining of seizures, changes in sensation/weakness and speech difficulties.
On CT/MRI you see an ill-defined irregular mass that does NOT enhance with contrast.
Gross: normal gray and white matter are discolored and there is a burred junction
Histology: incomplete, but well-differentiated astrocytic cells with stellate configuration infiltrating normal axons and glial cells. There is NO vascular infiltration, necrosis
or mitotic figures.
What does the patient most likely have? What protein can you stain for to verify your suspicions?
Diffusely infiltrating astrocytoma
Stain for GFAP [glial fibrillary acidic protein] because it is in the cytoplasm of astrocytic cells but NOT epithelial, melanocyte, hematolymphoid
What genetic mutation is common for diffusely infiltrating astrocytomas?
What is the consequence and how can it be used for diagnosis?
What genetic mutation has been reported in over 65% of low grade astrocytomas that progress to grade 4 tumors [glioblastomas]?
- IDH - isocitrate dehydrogenase an enzyme of the Kreb cycle
Normal IDH –> a-ketoglutarate
Mutated IDH–> 2-hydroxyglutarate
2hydroxyglutarate can be detected by magnetic resonance spectroscopy to assess CNS lesions of uncertain type and to manage gliomas
TP53 is mutated in most cases that progress to grade 4 glioblastomas.
What is the mean survival for patients with diffusely infiltrating astrocytomas?
What patients have an improved overall survival?
6-8 years after surgery.
IDH-mutated patients have a better survival than those with IDH wildtype
What name is given to diffusely infiltrating astrocytomas when they are grade 4?
What percent of intracranial neoplasms does it make up?
What age patient is affected?
Glioblastoma is the most frequent PRIMARY brain tumor –12 to 15% of intracranial neoplasms
Affects 45-70 year olds
A woman brings her husband into the hospital. She said over the past 3 months he has begun having seizures, personality changes, and headaches.
You do a CT and note a unilateral irregularly shaped lesion centered in the white matter with a peripheral zone of contrast [high cellularity] enhancement around a dark central area [necrosis].
Gross: irregular, poorly delineated masses with grey, yellow-white, and reddish/brown/green areas.
Histology:
- poorly differentiated glial cells, some with stellate projections
- cells are crowded more centrally
- pleiomorphic nuclei, mitotic figures
- tumor necrosis, microvascular proliferation
What is the likely diagnosis?
What is the prognosis?
Diffusely infiltrating astrocytoma WHO 4
Gross: grey= neoplastic cells, yellow = necrotic, red/green = recent and remote hemorrhage
Histology:
-vascular infilatration and tumor necrosis differentiate WHO2 from WH1O4
Prognosis = less than 1 year
How do primary and secondary glioblastomas differ in terms of presentation and genetics?
Primary= short clinical history, no clinical evidence of low grade precursor lesion.
*amplification of EGFR, loss of chromosome 10
Secondary = younger patients [<45] and progress from a lower grade infiltrating astrocytoma
*TP53 mutation, IDH mutation
A 40-60 year old patient presents with seizures and a headache. He has had a long pre-operative history of neurologic signs and symptoms.
CT shows a mass in the cerebral cortex and subcortical white matter. The lesion has foci of calcification.
Grossly the tumor is greyish-pink and is soft and gelatinous
Histology shows monomorphic round/oval cells that appear to be “fried eggs”. There are few or no mitotic figures.
What is the likely diagnosis and what grade is it?
What would the grade be if there were mitotic figures?
Fried egg = oligodendroglioma
No mitotic figures = grade 2
Mitotic figures = grade 3
What genetic changes are associated with oligodendrogliomas?
- loss of heterozygosity {LOH} on the long arm of chromosome 19 and LOH of the short arm of chromosome 1 [1p and 19q]
- IDH [same as with astrocytomas grade 2,3]
What is the prognosis for oligodendroglioma grade 2 and 3?
What improves prognosis?
Grade 2 = 5-10 years
Grade 3 = 2-7 years
Patients with tumors that have deletion of 1p and 19q have greater survival
Where type of cancer is the majority of CNS mets?
How do they get into the CNS?
Carcinomas from outside the CNS get into the CNS via hematogenous spread
How does the incidence of CNS mets change with age?>
Below 25 = 1/100,000
Above 60= 30/100,000
What is the location of the majority [80%] of the mets to the brain?
What layer of the spinal cord are mets most likely to go to?
80% of mets in the brain are in the cerebrum near the junction of cortex and white matter
15% in the cerebellum
Majority of spinal cord tumors go to epidural space and are extensions of mets to the vertebrae. [other locations are intramedullary, subarachnoid, leptomeningeal]
50% of mets to the brain come from ________.
15% are from __________. 10% are __________.
50% are from the lungs
15% breasts
10% melanoma
[a lot are renal cell carcinoma as well]
A patient has an intramedullary spinal cord met. Where is it most likely that it originated?
lungs
A patient presents with a met that is causing epidural spinal cord compression. What 3 locations are most likely for the primary tumor?
- breast
- lungs
- prostate
A person presents a diffuse infiltration of the leptomeninges by mets. What are the likely locations of the primary lesion?
leukemia
lymphoma
melanoma
carcinoma
On CT scan, what percent of patients will have 1 met? 2?
How will they look on CT?
1= 50% 2 = 20%
They will be discrete masses with contrast enhancement and surrounding edema
What 3 brain mets will often be hemorrhagic?
- lung and renal cell carcinomas
- chormiocarcinoma
- melanoma
What is the median survival for patients with brain mets?
What factors play a role in prognosis?
2-7 months
Prognosis depends on
- age
- Karnofsky performance
- number and location of mets
- response of mets to radiation
What WHO grade is pilocytic astrocytoma?
Who is it most likely to present in and in what area of the brain?
It is grade 1 [mass expanding lesion, not tissue infiltrating].
It affects mainly children and patients under 20 and 85% are cerebellar astrocytomas
A 15 year old presents with headache, nausea, vomiting and clumsiness.
You do a CT and see a well-circumscribed, contrast-enhancing lesion.
Histology shows neoplasms of cells with stellate cytoplasm. The tumor looks biphasic with areas of densely packed, elongated, bipolar astrocytes adjacent to loose stellate astrocytes.
Some cells have Rosenthal fibers [eosinophilic cigar masses].
What is the likely diagnosis?
Pilocytic astrocytoma
Describe the histology of a pilocytic astrocytoma.
- Biphasic architecture with:
- densely packed, elongated bipolar astrocytes
- loose stellate astrocytes - Rosenthal fibers- cigar shaped, protein masses that are eosinophilic
- eosinophilic granular bodies
What genetics are associated with pilocytic astrocytoma?
- 15% have NF1 mutations
- 17q deletion
What is the prognosis for pilocytic astrocytoma?
It depends on:
- tumor location
- extent of resection
- presence/absence of NF1
5 ,10 ,20 year survival rate for cerebellar is 85, 81, 79
What CNS tumor originates near the walls of the ventricles or central canal of the spinal cord and grows slowly but doesn’t infiltrate?
Ependymomas
What is the WHO grade of ependymomas?
What age do they occur in?
What location in the CNS are they typically found?
Grade 2,3
All ages [but come up a lot in children]
70% are intracranial and of that, 70% are in the posterior fossa.
___________tumors may present with seizures or focal deficits. _______________ tumors may cause ataxia, dizziness, or visual disturbances often with nausea, vomiting and headache from increased intracranial pressure.
____________ tumors cause motor and sensory symptoms.
Supratentorial = seizures, focal deficits
Posterior fossa = dizziness, ataxia, headaches
Spinal cord tumors = motor and sensory
A man presents with ataxia, dizziness and visual disturbance. You do imaging and note varying degrees of contrast enhancement with some hemorrhage, calcification and cysts.
Histology shows cells with monomorphic nuclei, long fibrillar cytoplasmic processes. The cell bodies are clustered around a blood vessel forming a pseudorosette.
What is the likely diagnosis?
Ependymoma
What are the most frequent cytogenetic alterations associated with ependymoma?
- monosomy 22
2. deletions or translocations of 22q
What familial disorder are spinal ependymomas associated with?
NF2
Based on location of ependymoma, rank survival rates from best to worst.
- spinal
- supratentorial
- posterior fossa
A 13 year old patient presents with headache, lethargy and vomiting, truncal ataxia and disturbed gait.
On imaging, you see a solid mass that is contrast enhancing in the vermis.
Histology shows small, poorly differentiated cells with very little cytoplasm [small blue cells] in monotonous sheets or rosettes.
There are a lot of mitotic figures and tumor necrosis.
What is the likely diagnosis?
What immunochemistry stains could you do?
Medulloblastoma
- GFAP stain
- synaptophysin or neurofilament stains
What is the most frequent genetic alteration in medulloblastomas?
- loss of 17p [TP53 loss]
- isochromosome 17q [TP53 loss]
- MYC gene amplification
What cells compose a neurofibroma?
Is the tumor low or high grade?
It is a low grade tumor [WHO 1] composed of differentiating:
- schwann cells
- fibroblasts
What are the 4 sources/locations for neurofibromas?
- cutaneous peripheral nerves [circumscribed or diffuse]
- large peripheral nerves [circumscribed]
- large nerve trunks [multinodular/plexiform]
- diffuse soft tissue tumors
What is the gross appearance of a cutaneous peripheral neurofibroma?
Circumscribed tumor in the skin that is nodular and gray with a glistening surface
What is the gross appearance of a large peripheral nerve neurofibroma?
fusiform and gelatinous
What is the gross appearance of a plexiform neurofibroma?
multinodular involving:
- multiple trunks in a plexus
- multiple fascicles of a large nerve
What genetics are associated with neurofibromas?
NF1 tumor suppressor from 17q is lost
**multiple neurofibromas is the hallmark of NF1
How does prognosis differ for the different types of neurofibromas ?
Prognosis is good for
- cutaneous peripheral nerve neurofibromas
- peripheral nerve neurofibromas
- SOME soft tissue tumors [although sometimes for them you don’t get a full resection]
Not as good:
-plexiform tumors can progress in grade
What is the inheritance pattern of neurofibromatosis type 1? What is the gene mutation?
What is the prevalence?
What are the 5 manifestations that make diagnosis of NF1 likely?
Autosomal dominant mutation of NF1 gene on chromosome 17q12 which makes neurofibromin. It is thought to be a tumor suppressor
1/4000
- multiple neurofibromas [hallmark= plexiform]
- multiple cafe-au-lait spots
- axillary/inguinal freckling
- optic nerve pilocytic astrocytoma
- iris harmartomas [Lisch nodules]
What cells make up a schwannoma?
What is the WHO grade?
What age/sex is most affected?
It is incompletely differentiated schwann cells [myelinating cells of PNS]
WHO 1
30-60 year old women
What are the 4 most common locations of schwannomas?
- nerves of head
- nerves of neck
- extensor aspects of extremities
- vestibular division of CN8
What is the typical presentation of a schwannoma?
It oresents like a peripheral mass.
Spinal tumor = pain and sensory symptoms
CN 8 = tinnitis, loss of hearing, facial paralysis
A 45 year old woman presents with tinnitis, loss of hearing and facial paralysis.
You do a CT and see a well-circumscribed contrast enhancing mass.
Histology of the mass shows biphasic architecture with:
- packed elongated spindle shaped cells in intersecting fascicles [antoni A]
- loose stellate cells [antoni B]
What nervous system tumor should you be considering and what is the location?
Schwannoma on CN 8
What is the histology of a typical schwannoma?
Biphasic architecture:
- Antoni A = packed, elongated spindle cells arranged as intersecting fascicles
- Antoni B = loose stellate cells
- Verocay body = antoni A arranged in 2 parallel groups of palisaded nuclei
What genetic changes are associated with schwannomas?
usually they are single and sporadic, but if there are multiple it is associated with NF2
What is the inheritance pattern of NF2?
What cells are dysplastic/neoplastic?
It is an autosomal dominant disorder where:
- meningothelial cells
- schwann cells
- glial cells
are dysplastic and neoplastic
What is the diagnostic hallmark of NF2?
- bilateral 8th nerve schwannomas
- multiple meningiomas
- spinal ependymomas
What genetic changes are present in NF2?
NF2 gene is on 22q12
- protein merlin
- tumor suppressor
