CNS Tumors Flashcards
1
Q
CNS Tumors
Epidemiology
A
-
Adults
- 1° CNS tumors uncommon in adults
- Represent 1.2% of all autopsy deaths and 9.2% of all primary neoplasms
- Gliomas are the most common
-
Children
- Tumors of the CNS account for nearly 20% of all cancers of childhood
2
Q
CNS Tumors
Clinical Features
A
- Clinical course is strongly influenced by patterns of growth and location
- Low grade + diffuse infiltration ⇒ serious clinical deficits and poor prognosis
- Location & infiltrative growth ⇒ may not be amenable to complete surgical resection w/o compromising neurologic function
- Any CNS neoplasm may have lethal consequences if situated in a critical region of the brain
3
Q
CNS Tumor
Origin
A
No longer thought that these tumors derive from their specific, mature cell types (astrocytes, oligodendrocytes, and ependymal)
Arise from a progenitor cell that preferentially differentiates down one of the cellular lineages
4
Q
Primary CNS Tumor
Growth Pattern
A
Primary tumors in the CNS are typically diffusely infiltrative
- Spread along nerve fascicles and in the subpial and subependymal regions
- Extra neural spread of tumors is rare and usually seen only after multiple surgical interventions
- Metastases of CNS tumors are not common
- More malignant ones, especially medulloblastoma may spread along the pathways of cerebrospinal fluid flow
5
Q
Metastatic CNS Tumor
Growth Pattern
A
- Often reaches CNS as a tumor embolus ⇒ lodges at the grey-white junction
- They are rarely infiltrative, and instead push brain tissue away from growing borders
- Because of the mechanism of tumor embolization, tumor spread often is microscopically perivascular
6
Q
Supratentorial Tumors
A
- Tumors occur above the tentorium ⇒ in the hemispheres
- Comprise 2/3 of the tumors in adults
- Comprises 1/3 of the tumors in children
- Of these supratentorial tumors: gliomas > meningiomas > metastases
7
Q
Infratentorial Tumors
A
- Tumors occurring in the posterior fossa ⇒ in the cerebellum and brain stem
- Comprise 1/3 of the tumors in adults
- Comprises 2/3 of the tumors in children
8
Q
Cerebral Edema & Herniation
A
9
Q
Spinal Tumor
Classification
A
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Extradural
- Form outside the dura, usually in the vertebral body
- The most common extradural tumors in adults are metastases, followed by primary tumors of bone
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Intradural
- Tumors within the intradural compartment includes:
- Subdural space between the dura and the spinal cord
- Spinal cord itself (intramedullary tumors)
10
Q
Spinal Tumor
Types
A
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Meningiomas are the most frequent type ⇒ subdural
- Usually attached to the inner surface of the dura
- Ependymomas ⇒ intramedullary
- Astrocytomas ⇒ intramedullary
11
Q
Classification of Brain Tumors
A
In 2016 the WHO completely revised the classification:
- Previously based on histologic type ⇒ 2007 classification
-
Now utilizes both histologic and molecular data ⇒ 2016 classification
- Groups have changed dramatically
- In discordant cases, genotype trumps histologic phenotype
- ‘Not Otherwise Specified’ (NOS) category used for cases where genetic analysis is not possible or inconclusive
- It does NOT serve as a default category
12
Q
Grading of Brain Tumors
A
WHO grade determination is made based upon histology
13
Q
CNS Tumor
Diagnosis & Naming
A
- Histopathological name followed by the genetic features
- Example: Diffuse astrocytoma, IDH-mutant
-
If more than one genetic determinant, all included
- Example: Oligodendroglioma, IDH-mutant and 1p/19q codeleted
-
For tumors lacking genetic mutation, the term wildtype can be used if an official wildtype exists
- Example: Glioblastoma, IDH-wildtype
-
For a tumor lacking a diagnostic mutation or where analysis cannot be performed, a NOS designation is given
- Example: Diffuse astrocytoma, NOS
14
Q
Gliomas
Overview
A
- Most common group of primary brain tumors
- Arises from a progenitor cell that preferentially differentiates along one of the cellular lineages
- Previously classified based on their morphologic resemblance to different types of glial cells
-
Molecularly distinct family of neoplastic lesions, independent of their histologic patterns
- Currently dx based upon combined histologic patterns and molecular characterization
- Majority in adults are diffuse astrocytomas and oligodendrogliomas
15
Q
Gliomas
Genetic Alterations
A
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IDH1 or IDH2 Mutations
- Isocitrate dehydrogenase (IDH1 – cytosolic, IDH2 – mitochrondrial)
-
Gain of function mutation
- Mutated cells: α-ketoglutarate → “oncometabolite” 2-hydroxyglutarate ⇒ metabolic reprogramming of the cell
- Remain in a stem cell-like state ⇒ more prone to self-renewal and tumorigenesis
- Most common IDH1 mutation at codon 132 (85-90% cases) ⇒ can be detected w/ immunohistochemical stain
- IDH2 mutations ⇒ require sequencing or other technique for detection
- IDH mutation analysis REQUIRED for classification of Diffuse Glioma
-
Mutation is a specific tumor marker ⇒ is NOT seen in reactive conditions
- Present in 85-90% of low-grade gliomas in adults
- Mutation almost never found in children (< 14 years)
- Grade for grade, IHD mutated tumors have a better prognosis than IDH wild type tumors
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ATRX Mutations
- Loss of function mutation
- ATRX normally suppresses recombination events that can preserve telomere length ⇒ “alternative lengthening of telomeres”
- Immunohistochemical stain specific for normal protein ⇒ ⊖ in mutated cells
-
1p 19q Deletions
- Co-deletion of 1p and 19q required for dx of oligodendroglioma
- FISH analysis for dx
- Mechanism for ∆ tumor morphology and response to tx unknown
16
Q
Astrocytoma
Overview
A
- Infiltrating astrocytomas account for ~ 80% of adult primary brain tumors (4th– 6th decade)
- Usually in the cerebral hemispheres
- Also in cerebellum, brainstem, or spinal cord
- Clinical: Present w/ seizures, headaches and focal neurologic deficits
- Spectrum of histologic differentiation that correlates well w/ clinical course and outcome
17
Q
Astrocytoma
Subtypes
A
Histologically stratified into three groups w/ increasingly poor prognosis:
Diffuse astrocytoma (grade II)
Anaplastic astrocytoma (grade III)
Glioblastoma (grade IV)
18
Q
Diffuse Astrocytoma
A
“Infiltrating Astrocytoma”
- Poorly delineated hemispheric mass
- ↑ Density of astrocytes w/o histologic features of high grade astrocytomas
- May be low or high grade at presentation
- Survival in low grade up to 20 years after primary dx
- Most will evolve into a high grade, aggressive tumor ⇒ Secondary GBM
-
IDH analysis required for dx of diffuse astrocytoma in adults
- IDH status more prognostically important than grade
-
Pediatric astrocytomas have different genetic abnormalities than adult tumors
- IDH mutation almost never found in children (<14 years)
19
Q
Anaplastic Astrocytomas
A
- High grade astrocytoma
- Densely cellular w/ greater nuclear pleomorphism
- Mitotic figures are often observed
20
Q
Glioblastoma (GBM)
A
- High grade astrocytoma
- Variation is characteristic w/ some areas firm and others are soft due to necrosis +/- cystic degeneration and hemorrhage
- Microscopic is similar to anaplastic astrocytoma plus necrosis and/or vascular/endothelial cell proliferation
- Necrosis in glioblastoma shows a pseudo-palisaded appearance
- 10% survival at two years
21
Q
Glioblastoma (GBM)
Types
A
-
Primary GBM
- Majority of cases
- Arise de novo in older patients
- Typically IDH-wildtype
- Poor prognosis
-
Secondary GBM
- Minority of cases
- Younger patients
- Arise from a lower grade precursor lesion
- IDH mutations common
- Better prognosis
22
Q
Localized Astrocytomas
A
23
Q
Pilocytic Astrocytoma
A
- Most common localized astrocytoma
- Tumors of children and young adults
- Locations: cerebellum >> third ventricle, optic pathways, spinal cord >> cerebral hemispheres
- Relatively benign behavior
- Limited infiltration
- Bipolar cells w/ long, thin “hairlike” processes that form dense fibrillary meshwork
- Rosenthal fibers and eosinophilic granular bodies are characteristic findings
- Necrosis and mitosis uncommon
- Commonly have activating mutations or translocations of BRAF ⇒ ⊕ MAPK signaling pathway
- May be treated w/ BRAF inhibitors, esp when location prevents removal
- Do not have mutations in IDH1 and IDH2
24
Q
Oligodendroglioma
A
Infiltrating glioma comprised of cells that resemble oligodendrocytes
- 5-15% of gliomas
- 4thto 5th decades
- Clinical: often several years of neurologic complaints, often including seizures
- Cerebral hemispheres ⇒ white matter
- Well circumscribed, gelatinous w/ cysts, focal hemorrhage, and calcification
- Microscopically: sheets of cells resembling normal oligodendrocytes w/ clear, vacuolated cytoplasm and a delicate network of anastomosing capillaries
- Calcification (90% of tumors) ⇒ ranges from microscopic foci to massive depositions
- Mitotic activity is minimal or absent
- WHO grade II lesions
- IDH mutation and 1p/19q codeletion REQUIRED for diagnosis
- Pediatric tumors often do NOT demonstrate IDH mutation and 1p19q codeletion ⇒ these tumors currently classified NOS category
25
Q
Ependymoma
A
-
Often arise next to the ependyma-lined ventricular system
- Tumors of fourth ventricle during first two decades of life
-
Tumor of spinal cord in middle life
- Neurofibromatosis type 2 (NF2) pts commonly have spinal cord lesion
- Tumors show abnormalities in the NF gene on chromosome 22 are common
- Grading difficult and of questionable clinical utility
- Gross: usually solid and sharply demarcated from surrounding tissue
- Micro: ependymal canals – rosettes - tumor
27
Q
Medulloblastoma
A
- Malignant embryonal tumor
- Predominantly children
-
Exclusively in the cerebellum
- Histologically similar lesion may arise in the hemispheres ⇒ was termed CNS PNET, now embryonal tumors
- Largely undifferentiated and corresponds to WHO grade IV
- Often well-circumscribed, gray, and friable
- Rapid growth may occlude the flow of CSF ⇒ hydrocephalus
- Microscopic very densely cellular w/ sheets of anaplastic cells and rosettes
- Mitoses are abundant
- Frequently disseminates along the CSF flow ⇒ ependymal and subarachnoid tumor implants
- ∆ in signaling pathways involved in normal cerebellar development ⇒ basis for classification
- Treatment: aggressive surgical removal followed by radiation of brain and spinal cord +/- chemo
33
Q
Meningioma
A
- Predominantly benign tumors of adults
- Arise from meningothelial cells of the arachnoid
-
Attached to the dura
- Found along external surfaces of brain and within ventricular system
- Prior radiation therapy to the head and neck is a risk factor
- Female to male = 3:2
- Rounded masses w/ well-defined dural bases that compress underlying brain but are easily separated from it
- Microscopically show whorls and calcifications (psammoma bodies)
- Low risk of recurrence or aggressive growth ⇒ WHO grade I/IV
- Usually diagnosed by CT or other scans
- Does not invade the brain
- Most common cytogenetic abnormality is loss of 22q
- Seen in 50-60% of sporadic meningiomas
34
Q
CNS Lymphomas
A
- Can be primary in CNS or metastatic
- Diffusely infiltrates the brain
- Microscopically perivascular collections of lymphocytes
35
Q
Primary CNS Lymphoma
A
- 2% of extranodal lymphomas and 1% of intracranial tumors
-
Most common CNS neoplasm in immunosuppressed individuals (AIDS & transplant patients)
- Immunosuppressed patients ⇒ associated w/ Epstein-Barr virus
- Transplant patients ⇒ associated w/ a systemic post-transplantation lymphoproliferative disorder
- Often multifocal within the brain parenchyma
- Involvement outside of the CNS in lymph nodes or bone marrow is a rare and late complication
- Majority are B-cell origin
- Aggressive and have worse outcomes vs comparable tumors in non-CNS sites
37
Q
CNS Metastasis
A
- Represents 25-50% of all brain tumors
- More common in older age group
- Most common primary sites: lung, breast, skin (melanoma), kidney, and GI tract ⇒ ~ 80% of all metastases
- Usually multiple lesions ⇒ well-circumscribed mass at the junction of the white and grey matter surrounded by significant edema
- Microscopically – looks like the primary tumor
- Treatment of solitary brain metastases improves the quality of the patient’s remaining life
39
Q
Carcinomatous Meningitis
A
- Different presentation of metastatic tumor
- Tumor deposits throughout CNS in the subarachnoid space ⇒ widespread neurological dysfunction
- Can present as pain, cranial and peripheral nerve palsies or diffuse brain dysfunction
- Seen most often w/ adenocarcinomas, including carcinomas of the breast or stomach
- Can treat w/ radiation and chemotherapy
40
Q
Traumatic Neuroma
A
- Peripheral nerve tumor
-
Non-neoplastic proliferation associated w/ previous injury of a peripheral nerve
- If regenerating axons do not line up w/ transected end of the nerve ⇒ traumatic neuroma
- Clinically: presents w/ painful localized nodule following an injury
- Microscopically consists of a haphazard mixture of axons, Schwann cells, and connective tissue
41
Q
Schwannoma
A
- Peripheral Nerve Tumors
-
Encapsulated nerve sheath tumor consisting microscopically of two components:
- Highly ordered cellular component (Antoni A area) (Verocay bodies)
- Loose myxoid component (Antoni B area)
- Encapsulation, two types of Antoni areas, uniformly intense immunostaining for S-100 protein distinguish schwannoma from neurofibroma
- Typically benign
- Adults in 5th and 6th decades
- 90% sporadic, 3% in patients w/ NF2, rare in NF1
- Solitary, circumscribed lesion
- Compresses but does not invade nerve
- Mostly seen in proximal nerves or spinal roots
- Potential for surgical removal
42
Q
Neurofibroma
A
Benign nerve sheath tumor of the PNS
2nd to 3rd decade
44
Q
Diffuse Neurofibroma
A
- Close association w/ neurofibromatosis 1 (NF1)
- Infiltrative proliferations that can take the form of large, disfiguring subcutaneous masses
45
Q
Plexiform Neurofibroma
A
- Virtually pathognomonic of neurofibromatosis 1 (NF1)
- Grow diffusely within the confines of a nerve or nerve plexus
- Grossly: fusiform, non-circumscribed enlargements of nerve, solitary or multiple, seen in distal part of nerve
- Microscopic: interlacing bands of spindle cells w/ elongated nuclei
- Infiltrate nerve and are difficult to separate from nerve bundle, hard to remove
- Can undergo malignant change and infiltrate adjacent tissue
46
Q
Neurofibromatosis Type 1
Diagnosis
A
47
Q
Malignant Peripheral Nerve Sheath Tumor (MPNST)
A
- Neoplasms in adults
- Schwann cell derivation and sometimes a clear origin from a peripheral nerve
-
May arise from transformation of a neurofibroma, usually plexiform type
- 3% to 10% of all patients w/ NF1 develop a malignant peripheral nerve sheath tumor during their lifetime
- Large, poorly defined masses
- Microscopically tumors are highly cellular and exhibit features of overt malignancy
- Anaplasia, necrosis, infiltrative growth pattern, pleomorphism and high proliferative activity
48
Q
CNS Tumors
Summary
A
49
Q
Peripheral Nerve Sheath Tumors
Summary
A
