Neuro - CNS - Neoplastic Diseases Flashcards
1
Q
Neoplastic Diseases - General Presentation
A
- Patient usually presents with either:
- subacute progression of a focal neurological deficit
- Non-focal neurological disorder (HA, dementia, gait dysfunction, etc.)
- **Malaise, weight loss, anorexia and fever are usually suggestive of metastasis
2
Q
Classification of Astrocytomas - Grade 1
A
- Prognosis - variants of astrocytoma with excellent prognosis
- Clinical Findings - varied
- Radioogy - varied
- Histopathology - varied
- Examples - juvenile pilocytic astrocytoma; subependymal giant cell astrocytoma; pleomorphic xantho-astrocytoma
3
Q
Classification of Astrocytomas - Grade II
A
- Prognosis - can remain static or convernt into a more aggressive form of tumor
- Clinical - presents with seizures, headaches or localizing signs; age range in 20-30 years deterioration in 93 months post diagnosis
- Radiology - Vague, hemispheric white matter hypo-densities
- Histopathology - Macroanatomy: grossly poorly defined area of expanded, discolored white matter, often obscuring the grey-white junctions; Microanatomy - infiltrating astrocytic “naked nuclei”
- Examples - Fibrillary Astrocytoma
4
Q
Classification of Astrocytomas - Grade III
A
- Prognosis - more aggressive form of tumor
- Clinical - presents with edema and rapid clinical deterioration, 12 months post diagnosis
- Histopathology - a more cellular tumor with nuclear pleomorphism and mitotic figures
- Examples - Anaplastic astrocytoma
5
Q
Classification of Astrocytomas - Grade IV
A
- Prognosis - most aggressive form of glial tumor, highly malignant, very poor prognosis
- Clinical - very rapid deterioration, 5 months post prognosis
- Radiology - Large mass with necrotic core; ring enhancing lesion
- Histopathology - Macro: variegated gross appearance, with areas of solid tissue, necrosis and hemorrhage.
Micro: mitotic figures, necrosis, and vascular endothelial proliferation (“glomeruloid”) - Examples - glioblastoma multiforme
6
Q
Pilocytic Astrocytoma
A
- Two major forms of astrocytes are recognized: those with narrow distributions, such as the pilocytic astrocytoma and those with diffuse distributions termed astrocytomas.
- Grade I - is reserved for pilocytic astrocytoma.
- It is a realtively benign, slow growing astrocytoma of children, typically seen in the cerebellum
- AKA - spongioblastomas, juvenile astrocytoma
7
Q
Pilocytic Astrocytoma - History
A
- Accounts for 6% of intracranial tumors; incidence is >1 per 100,000 cases per year
- Most frequent brain tumor of infants
- Peak incidence is 8 to 13 years of age
- Location:
- cerebral hemispheres and spinal cord in older children
- optic nerve, optic chiasm, brainstem and cerebellum in younger children
- hypothalamus, pineal gland
- Frequency of Distribution: (descending order)
- cerebellum
- optic nerve and chiasm (common in patients with NF-1)
- cerebral hemisphere - medial aspect of temporal lobe
- brainstem
- Pathology
- Bipolar processes (hair-like)
- Rosenthal fibers: extracellular protein globules
8
Q
Pilocytic Astrocytoma - Presentation
A
- Slow growing, thus clinical history may precede diagnosis by months to years
- Focal neuro signs and symptoms depend on location:
- cerebellum > ataxia and increased ICP/hydrocephalus, seizures
- optic system > decreasing visual acuity
- Hypothalamic involvement > endocrine abnormalities
- brainstem involvement > cranial nerve defects
9
Q
Pilocytic Astrocytoma - diagnostic testing
A
- CT imaging - enhanced
- MR imaging
- Stereotactic biopsy and cytology
10
Q
Fibrillary Astrocytoma-
A
- Two major forms of astrocytes are recognized: those with narrow distributions such as the pilocytic astrocytoma and those with diffuse distributions termed astrocytomas.
- Astrocytomas are the most common CNS neoplasms in adults (80%)
- They are malignant, relentlessly progressing, and arise almost exclusively in cerebral hemispheres.
- Diffuse Astrocytomas have 3 grades:
- Grade II Fibrillary
- Grade III Anaplastic
- Grade IV Glioblastoma
- Of these grades, the Fibrillary astrocytoma is the most differentiated and slowest growing neoplasm. They also feature diffuse infiltration of surrounding structures.
AKA - well-differentiated astrocytoma, fibrillary diffuse astrocytoma, low grade astrocytoma
11
Q
Fibrillary Astrocytoma- History
A
- Preferential location is in the cerebral hemispheres
- Grade II fibrillary astrocytomas account for 25% of all gliomas in the cerebral hemispheres
- young, 20-30 years of age
- associated with mutation of chromosome 17 > inactivation of p53 suppressor and overexpression of PDGF-A
- survival of 5-6 years after presentation
12
Q
Fibrillary Astrocytoma- Presentation
A
- Seizures
- headaches
- Focal neurologic signs related to location of tumor
13
Q
Fibrillary Astrocytoma- Diagnostic Testing
A
- CT shows vague hemispheric white matter hypodensity
- MRI
- Angiography can be useful
- Lumbar puncture and CSF cytology
- Stereotactic biopsy and cytology
- infiltrating astrocytes with “naked nuclei”
- mitosies present, cellular
- usually do not resect because tumor is so infiltrated
- chemotherapy and radiation not used because side effects worse than tumor.
14
Q
Anaplastic Astrocytoma
A
- Diffuse astrocytomas have three grades:
Grade II - fbrillary
Grade III - Anaplastic
Grade IV - Glioblastoma - Anplastic astrocytomas represent a form of diffuse astrocytoma characterized focal of dispersed anaplasia (reversion of cells to an immature or less differentiated form).
- The anaplastic nature indicates a higher grade of malignancy.
AKA - AA, Malignant astrocytoma, high grade astrocytoma
15
Q
Anaplastic Astrocytoma - History
A
- Primary brain tumorshave an incidence of 14/100,000
- Gliomas represent 40% of primary brain tumors
- Anaplastic astrocytomas represent 8.3% of all CNS gliomas
- In order of decreasing frequency, AAs appear in:
- Frontal > parietal > temporal > Occipital lobes
- Mutations of chromosomes 9 & 19
- Track along white matter pathways to infiltrate adjacent hemisphere -
- Can metastasize down spinal cord but are rare outside of CNS
- Survival of <3 yrs
16
Q
Anaplastic Astrocytoma - Presentation
A
- Rapidly progressing tumor
- Seizures
- Headache
- Focal neurologic signs related to the location of the tumor
17
Q
Anaplastic Astrocytoma - Diagnostic Testing
A
- CT imaging
- MR imaging
- Angiography can be useful
- Lumbar puncture and CSF cytology
- Stereotactic biopsy and cytology
- uses computer imaging in at least two planes to guide tumor removal
18
Q
Glioblastoma Multiforme
A
- Grade IV Glioblastoma multiforme
- Grade IV is reserved for glioblastoma multiforme.
- It is the most aggressive of the glial tumors.
- It may be the result of progression of a fibrillary astrocytoma or it may present de novo in the elderly.
AKA - GBM
19
Q
Glioblastoma Multiforme - History
A
- Median survival rate is < 1 year
- longer survival correlates with younger age, performance status, extent of surgical resection
- Etiology - loss of p53
- Pathology -
- variegated (exhibiting different colors, irregular patches) gross appearance
- necrosis and hemorrhage
- mitotic figures (cells undergoing mitosis (elongated dark blob)
- glomeruloid: vascular endothelial proliferation
20
Q
Glioblastoma Multiforme - Presentation
A
- Focal neurological signs and symptoms depend on location
- Cerebellum involvement > ataxia, increased ICP, seizures
- optic system > decreasing visual acuity
- hypothalamic involvement > endocrine abnormalities
- brainstem involvement > cranial nerve defects
21
Q
Glioblastoma Multiforme - Diagnostic testing
A
- CT imaging
- ring enhancing
- loss of gray-white junction
- MR imaging
- Stereotactic biopsy and cytology
22
Q
Oligodendroma
A
- glial-cell tumors are highly infiltrative neoplasms believed to be derived from oligodendrocytes
23
Q
Oligodendroma - History
A
- comprise 5% of all intracranial neoplasms and 15-25% of gliomas in adults
- *** More benign and better prognosis then astrocytomas
- ***most frequently in cerebral hemispheres, frontotemporal region
- Occur less frequently in cerebellum, brainstem, and spinal cord.
- *** Tumors located near ventricular system can disseminate via CSF to the meninges
- Tumors typically have sharply demarcated margins
- become anaplastic when mitosis necrosis and nuclear atypia are more prominent
- mixed gliomas have astrocytomas and oligodendrocytes
- *** Inter-tumor calcification are common (40-80% of tumors), termed “brainstones”
- Genetic alterations include centromeric translocation of chromosomes 1p and 19q
- tumors with 1p deletion respond better to chemotherapy
- deletion of both 1p and 10q predicts durable response to chemotherapy
24
Q
Oligodendroma - classification and grading
A
Type: oligodendroglial tumors
(1) oligodendroma, grade: II, peak years: 30-55
(2) Anaplastic Oligodendroglioma, grade: III, age: 45-60
Type: Mixed Gliomas
(1) Oligoastrocytoma, grade: II, age: 35-45
(2) Anaplastic Oligoastrocytoma, grade: III, age: 40-50
25
Oligodendroma - Presentation
* Temporal Profile
- slowly progressing tumor
- long interval between clinical presentation and diagnosis
* Signs and Symptoms
- seizures
- headaches
- increased ICP
- can present initially with intracerebral hemorrhage
26
Oligodendroma - diagnostic testing
* CT imaging
* MR imaging
* Angiography can be useful
* Stereotactic biopsy: required for diagnosis
27
Meduloblastoma
* a malignant invasive embryonic tumor of the cerebellum most often seen in children and young adults
28
Meduloblastoma- History
* Meduloblastoma's account for 20% of CNS tumors in children
* * Most frequent malignant brain tumors in children
* five year survival rates are now greater than 50%
* Etiology - Male> Female
- Associated with chromosome 17p deletions > complete loss signals poor prognosis
29
Meduloblastoma - Pathology
* Exclusive occurence in the cerebellum
* Midline presentation in children; can be more lateral in adults
* Dissemination in CSF is common > non-communicating hydrocephalus
* Sheets of anaplastic cells
30
Meduloblastoma - Presentation
* clinical signs are typically less than three months in duration
* Common:
- headaches (ICP)
- persistent vomiting (ICP)
- truncal ataxia and sometimes spasticity
- papilledema (ICP)
- nystagmus
* Less Common
- limb ataxia
- Dysdiadokinesia
31
Meduloblastoma - Diagnostic testing
* CT imaging
* MR imaging
* Angiography canbe useful
* Lumbar puncture and CSF cytology
* Stereotactic biopsy and cytology
32
Meningioma
* Meningiomas are usually slow growing, benign tumors present on the meningeal layers surrounding the brain.
* They arise from the meningeal coverings of the brain.
33
Meningioma - Epidemiology
* Account for 13-20% of all primary intracranial neoplasms
* Most common in the 6th and 7th decade of life; rare in children
- when in children, often assoc. with NF-2 neurofibromatosis
* Risk factors -
- radiation and radiation therapy
- sex hormones, viral infections (SV-40) could play a role
34
Meningioma - Etiology
Grading:
* Grade 1 Meningioma (80%) - low risk of recurrence or aggressive growth
* Grade II - atypical meningioma
* Grade III - Anaplastic meningioma
* Grade IV - Meningeal sarcoma
* Progression of tumor grade type does occur and is associated with loss of chromosomal arms
35
Meningioma - Pathology
* Common locations
- convexities of the cranium
- along the falx
- skull base - can invade skull tissue but not related to malignancy
* usually solitary lobulated tumors attached to meninges
- can grow en plaque: sheet-like fashion along dural surface
* most likely develop from meningothelial (arachnoid) cells
* typical expand and replace CNS tissue but do not invade
36
Meningioma - presentation
* can be asymptomatic and an incidental finding on imaging
* **Focal neuro defects manifest due to compression of surrounding structures
* **Seizures (most common presenting complaint)
* ** Hemiparesis
* Gait disturbance
37
Meningioma - Diagnostic Testing
* CT scan
* MR imaging
* Angiography
38
Ependymomas
* tumors arising from the ependymal cells lining the ventricular system of the brain.
39
Ependymomas - Etiology
* Accounts for 5-10% of the primary brain tumors in 0-20 year olds
* ** The most common tumor of the 4th ventricle
* Second most common site is supratentorial in the lateral ventricles
* In adults, most common location is spinal cord
* Frequent in setting of NF2
* Supratentorial lesions: alterations in chromosome 9
* Spinal cord lesions: alterations in chromosome 22
40
Ependymomas - Pathology
* Well differentiated tumors with relatively slow growth
* Grade II tumors in the WHo classification
* Recurrence rate is high at 44%
* For fourth ventricle ependymomas, average survival post surgery - 4 years
* Leptomeningeal spread is common
* Secondary hydrocephalus is common due to progressive 4th ventricle obstruction
41
Ependymomas - Presentation
* Under the age of 3, clinical presentation involves:
- vomiting
- ataxia
- headache
- lethargy
- increased head circumference
- irritability
* Older children can shows:
- ataxia
- nystagmus
- gaze palsy
- hemiparesis
- neck pain
42
Ependymomas - Diagnostic testing
* CT Scan
* MR imaging
* Stereotactic biopsy
43
Craniopharyngiomas
* common childhood tumors that are derived from squamous epithelial cell rests that are remnants of Rathke's pouch.
* Typically these cystic tumors lie above the sella turcica (can disrupt pituitary function) and apply pressure to the optic chiasm and extends into the third ventricle.
44
Craniopharyngiomas - History
* Most typically seen in children, however can present at all ages
* Account for 7-10% of all childhood tumors
* WHO grade 1
45
Craniopharyngiomas - Presentation
* Headaches
* Bitemporal hemianopsia
* Diabetes insipidus
* Growth retardation
* Increased intracranial pressure
46
Ganglion cell tumors (Gangliocytomas)
* CNS tumor containing mature-looking neurons. When the presentation is mixed with glial-like cells, the tumor is termed a ganglioglioma
47
Ganglion cell tumors (Gangliocytomas) - History
* Very rare, occur usually within the first three decades of life
* Slow growing
* Commonly in:
- 3rd ventricle
- hypothalamus
- temporal lobe
48
Neurofibromatosis
Neurofibromatosis - a familial tumor syndrome, is in reality a complex spectrum of hereditary syndromes with neurocutaneous manifestations.
* Two basic types have been identified, Type i (NF-1), and Type II (NF-2), each with a separate genetic origin.
* * Type 1 - characteristic of a peripheral nervous system disease
* * Type II - characteristic of a central nervous system disease
49
Neurofibromatosis (NF-1 History)
* Autosomal dominant
* incidence est. 1/3000-4000
* **NF-1 located on chromosome 17q11.2
* **Encodes neurofibromin: appears to be a tumor suppressing, signal-transduction protein
* Possibly part of RAS family of GTPases
* Most NF-1 are benign, rare malignancies (<5-10%)
* Increased risk of multiple tumors, including neurofibromas, Schwannomas, astrocytomas, and meningiomas
50
Neurofibromatosis (NF - 2 History)
* Much less common then NF-1
* frequency of 1/40,000 or 50,000
* * NF-2 gene is located on chromosome 22q12
* * Encodes Merlin (or schwannomin): similar to cytoskeletal structural protein that functions as growth regulator
51
Neurofibromatosis (NF-1 Presentation)
* Von Recklinghausen's disease
- --cafe au lait spots are the most common presentation
- dermal lesions
- Plexiform (rope-like) lesions on spinal nerves
- palpable, rubbery, cutaneous tumors
- -- gliomas of the optic nerve
- -- pigmented nodules of the iris = Lisch nodules
52
Neurofibromatosis (NF - 2 Presentation)
* ** Bilateral eighth nerve schwannomas (>90%)
* multiple meningiomas
* Glioas (ependymomas) of the spinal cord
* Nodular Schwann cell growths in the spinal cord
* Meningoangiomatosis
* Glial hamartia
53
Lymphoma
* In primary CNS lymphoma, the disease initiates intracranially and metastatic extracranial spread is a late occurence in the process.
* Primary CNS lymphoma has to be differentiated from secondary CNS lymphoma that represents metastatic spread from a non-hodgkin lymphoma located elsewhere in the body.
54
Lymphoma - History
* Accounts for 1% of intracranial tumors
* Immunosuppression is a strong risk factor
- ---primary brain lymphoma (PBL) is a relatively common neoplasm in immunocompromised patients
- secondary BL casued by metastatic Non-hodgkin's lymphoma from elsewhere in the body.
55
Lymphoma - Pathology
* Single mass or multiple lesions within the brain parenchyma
* **Ring-enhancing on radiology > must be distinguished from abcess with abx treatment
* Majority of PBL are B cell lymphoma, large cell type
* ** Tumors in immunocompromised patients typically contain the Epstein-Barr virus genome
* composed on malignant lymphoid cells
- mitotic activity
- necrosis
- angiocentric pattern (surround vessels)
* PBL responds initially to radiation and steroid therapy, but tends to recur.
* Periventricular spread is common
56
Metastasis
* the spread of neoplastic growth to the CNS from a distant source
57
Metastasis - Etiology
* Intracranial masses appear in 25% of all patients with systemic cancer, of these:
- 15% are brain metastases
- 8 times more common than primary brain tumors
- 5% are leptomeningeal metastases
- 5% are metastatic lesion to the dura
58
Metastasis - Pathology
Primary lesion locations:
COMMON
* lung (35-64%)
- non-small cell carcinoma of the lung is most common primary site
- melanoma and small-cell carcinoma (less frequent) have greatest propensity to metastasize to brain
* breast cancers (14-18%)
* Skin melanoma (4-21%)
* renal cancer
* GI cancer
* NOTE: lung, breast, kidney and skin account for <90% of all metastatic brain tumors
UNCOMMON
- prostate
- pancreas
- tuerine
- ovarian
- hodgkin lymphoma
59
Metastasis - routes
* Mainly hematogenous spread
| * rarely direct spread from surrounding bone, meninges, or pituitary
60
Metastasis - Location
* Can occur anywhere in CNS
- cerebral hemispheres (80%)
- cerebellum (10-15%)
* ** Arterial watershed zones are most common sites, specifically MCA and PCA
* Predilection for gray-white junction
61
Metastasis - temporal profile
* Systemic disease usually presents initially, however CNS metastatic lesions can be initial presentation
* CNS metastatic lesion can manifest after primary systemic disease has been eradicated
62
Metastasis - Distribution
* Focal space-occupying lesions
| * Penumbra of edema enhances ICP increase
63
Metastasis - Specific Systems
* Headache (25%)
* Hemiparesis (25%)
* Seizures (15%)
* Cognitive or behavioral changes (15%)
64
Metastisis - Diagnostic Testing
* MRI with contrast
