CNS tumors Flashcards
(94 cards)
1
Q
- Childhood CNS tumors occur most often (75%) in the ______
- Adult CNS tumors are most often_____
- Localization of adult CNS tumors follows a mass distribution - most occur in the cerebral
hemispheres, most frequently frontal lobes as they are biggest
A
posterior fossa
supratentorial.
2
Q
General principle of CNS tumors
A
- Both low and high grade neoplasms have significant morbidity and mortality
- Diffusely infiltrative
- Involvement of critical anatomic areas
- Inability to resect critical anatomic areas
- Most of the time do not spread outside of brain (metastases: extremely uncommon)
• May spread through subarachnoid space
3
Q
The most common glial tumor
• Diffuse have an inherent tendency to progress to higher grades (anaplastic astrocytoma, glioblastoma) over time.
Annual incidence ~3-4 per 100,000
At least 80% are glioblastomas
A
Astrocytoma
4
Q
Clincal features of astrocytomas
A
- Seizures
- Focal neurologic deficits – gradual (not abrupt) onset
• Headaches
5
Q
-cellularity is moderately increased and occasional nuclear atypia
A
Grade 2 – astrocytoma (diffuse)
6
Q
increased cellularity, distinct nuclear atypia, marked mitotic activity
A
Grade 3 – anaplastic astrocytoma-
7
Q
pleomorphic astrocytic cells, brisk mitotic activity, prominent microvascular proliferation and/or necrosis and Psuedopalisading cells
A
Grade 4 glioblastoma multiforme –
8
Q
Gross features of astrocytoma
A
Space occupying lesion; low grade. see expanded and flattened gyri in right frontal lobe
9
Q
A
10
Q
What does GBM stain with? What histological features do we see?
A
with GFAP see vascular prliferation; lots of pleomorphic astrocytic cells with brisk mitotic activity
11
Q
- Most common glioma in children
- Typically present in 1st two decades
Found in posterior fossa
A
Pilocytic astrocytoma
12
Q
Clincal features of pilocytic astrocytoma (common childhood cancer)
A
- Most commonly occur in cerebellum
- May also occur in optic nerve, 3rd ventricle, hypothalamus, brainstem, and occasionally cerebral hemispheres
- Presentation with focal neurologic deficit, seizures, or S/S of increased intracranial pressure
13
Q
Kid presets with seizures and signs of increased cranial pressure. You see this on imaging. Dx adn prognosis
A
Pilocytic glioblastoma
slow glow, excellent prognosis, surgery = curative
14
Q
A
15
Q
Biphasic pattern: densely fibrillary (pilocytic) areas alternating with microcystic component and rosenthal fibers
A
Pilocytic astrocytoma
16
Q
• Adults in 5th to 6th decade
- Long history of progressive neurological symptoms (seizures, headache focal signs)
- Imaging – well defined hypodense/hypointense mass, may see calcification
A
Oligodendroglioma
17
Q
Prognosis of oligodendroglioma
A
median survival = 5-10 yrs for grade II
better then astrocytomas
18
Q
Oligodendroglioma: Allelic loss of chromosome ____ and ____ are predictors of prolonged survival and susceptibility to chemotherapy in anaplastic oligodendrogliomas
A
1p and 19q
good to have this shit!
19
Q
See fried egg appearane on histology with round nuclei
there are calcifications present
A
Oligodendroglioma
(fried eggs are Over easy)
20
Q
What do we see in grade 3 anaplastic oligodendroglioma
A
vascular porliferation and mitosis is increased; mass lesion that is invasive
(chicken wire is charcteristic)
21
Q
Typically occurs in children and young adults
Occurs along ventricular system, usually posterior fossa (4th ventricle)
Clinical S/S – _hydrocephalus, occasionally seizures _
A
Endymoma
22
Q
Grades of ependymomas and prognosis
A
- Ependymoma (WHO II)
- Anaplastic ependymoma (WHO III)
Prognosis – average survival for posterior fossa tumors is 4 years
23
Q
Solid or cystic tumors protruding from ventricular lining & filling ventricle
May invade brain parenchyma May disseminate through subarachnoid space
A
Ependyomama: pt presents with hydrocephalus
24
Q
See true rossettes (comlnar cells) arranged around a central lumen
A
Ependymoma
25
Highly cellular tumors with increased mitoses & vascular proliferation Still has perivascular pseudorosettes, and (sometimes) true rosettes
Anaplastic ependymoma
26
Etiology of Gliomas
Etiology of gliomas
* No cause identified in most common types • Familial tumor syndromes (rare: \< 5%)
* Li-Fraumenisyndrome(TP53germlinemutations) • Predominantly astrocytomas
* Turcotsyndrome(APC&DNAmismatchrepairgenes) • Glioblastoma or medulloblastoma
* Cowdensyndrome(PTENgenemutation) • Cerebellar gangliocytoma
* NF1,NF2,Tuberoussclerosis,vonHippel-Lindau(discussedlaterinthissession)
27
Environmental exposures associated with Gliomas
Only environmental factor definitively associated with increased risk of brain tumors is therapeutic radiation
• Example: Children who underwent prophylactic CNS irradiation for acute lymphocytic leukemia have increased risk of development of brain tumors
28
Typically found in **first two decades**
Occurs in **4th ventricle, lateral ventricle, 3rd ventri**cle and cerebello- pontine angle
Presentation with _hydrocephalus_
* _Overproduction_ of **CSF**
* _Obstruction_ of CSF flow
Choroid plexus papilloma
29
Choroid plexus papilloma vs carcinoma
Choroid plexus carcinoma
* Occurs in children \< 10 years
* Rare in adults
* Prognosis
* Choroid plexus papilloma – very good with surgical resection
* Choroid plexus carcinoma – poor prognosis
30
Well-demarcated, pedunculated or cauliflower-like mass
Papillomas do not invade adjacent parenchyma, (but carcinomas do)
choroid pleuxs papilloma
31
* Usually attached to roof of 3rd ventricle
* Intermittent obstruction of foramen of Munro (often positional)
* Positional headache
* Thin-walled cyst lined by cuboid/columnar epithelium
Colloid Cyst
32
* Usually in first three decades
* Long standing **history of seizures** is common
* Typically **supratentoria**l and in temporal lobe
* Imaging; **solid or cystic, often calcification**
* Surgical resection is usually **curative**
•No radiation or chemotherapy needed
Ganglioma
33
Typically a well-circumscribed mass, often with a cyst containing a mural nodule
histology: composed of atypical ganglion cells (neurons) and neoplastic glial compoenent
Ganglioma
34
Clincal features associated with medulloblastoma
Cerebellar dysfunction (ataxia) and increased intracranial pressure
35
Characteristic feature: tendency to spread through CSF pathways
medulloblastoma
36
Recently separated into four biologically distinct groups based upon genetic abnormalities
Each has difference risks of recurrence & progression (high, standard, low)
Traditionally a grade IV neoplasm, but now some subgroups have more favorable
outcomes
MEdulloblatoma
37
Treatement of medulloblastoma
Treatment – surgical resection followed by radiation (usually cranio- spinal)
• In some subgroups: with total excision and radiation, 5-year survival may be 75%
38
Solid well-defined homogeneous mass
Tendency to spread through sub- arachnoid space & form “drop” metastases
MEdulloblastoma
39
HOmer wright rosettes
synaptophysin immunoreactivity, hihgly cellular and compose of undifferenitated cells
Medulloblastoma
40
5-10% of primary intracranial neoplasms
Typically occur between 40-60 years
• Immunocompetent host – 55 yrs (rare, but increasing incidence)
* Immunocompromised host – 40 yrs • ~10%ofAIDSpatients,usuallylate-stage
* ~20%ofpost-transplantpatients
• Epstein-Barr virus association
Primary CNS lymphoma
41
Boring shit on Primary CNS lymphoma
98% B-cell; 2% T-cell
Symptoms are non-specific, referable to mass lesion
2/3 are supratentorial
Meningeal spread in ~25%
Poor prognosis – most die within one year
* RX – chemotherapy & radiation
* Spread of disease outside of CNS is rare
42
on MRI see contrast enhancing multiple periventricular lesions
pervientricular mass lesions with necrosis seen in Primary CNS lymphoma
43
Perivascular arrangement of neoplastic cells;make a cuff around the vessels
PRimary CNS lymphoma
44
* Most common **extra-parenchymal neoplasm of CNS**
* Clinical features: Occurs in middle to late adult life, W\>M
Symptoms dependent on location: may lead to increased intracranial pressure, focal signs, seizures
Imaging: dural based, usually well-defined, contrast-enhancing
Meningioma
45
Significance of presence of progesterone receptors on cells & increased occurrence in women is not understood
Associations: previous radiotherapy and NF2
Genetic abnormalities: monosomy of chromosome 22 or mutation of NF2 gene (on chr. 22)
Meningioma
46
Meningioma:
Significance of presence of\_\_\_\_\_\_ receptors on cells & increased occurrence in women is not understood
Associations: previous\_\_\_\_\_ and \_\_\_\_\_
Genetic abnormalities: monosomy of chromosome\_\_\_\_ or mutation of NF2 gene (on chr. 22)
progesterone
radiotherapy and NF2
22
47
Location of meningioma
Parafalcine, lateral sulcus, orbitofrontal cortex, cerebellopontine, thoracic spinal dura
48
FEature of menigioma:
Firm, well-defined, tan-white tumor often attached to dura
49
Typical (WHO grade I): \>90% are Grade I
• Excellent 5-year survival
• 20% recur within 10 years (when all was grossly resected)
Atypical (WHO Grade II): 5% are Grade II
• More mitoses, less differentiation, and sometimes brain invasion • 5-year recurrence = 40%, mortality = 20%
Anaplastic (WHO Grade III): 2% are Grade III • Even more mitoses and even less differentiation • median survival = 1.5 years
boring shit about menigioma
50
Describe histology of meningioma
sheets of tumor cells with indistinc borders: whorls and round to oval nuclie, disperesed chromatin with wispy eosinophilc cytoplasm
51
Meningioma, atypical & anaplastic features
Necorsis, mitosis, brain invasion
52
Mets to CNS
Metastatic tumors to the CNS
May be **first presentation of malignancy** (in 50%)
Most originate in the lung or breast carcinomas
• Other common sources are kidney, gastrointestinal tract, and skin (malignant melanoma) neoplasms
53
S/S of mets to CNS
what we see on radiograph
prognosis
Clinical S/S
• Headaches, focal neurologic signs, altered mental status
Radiographically – distinct contrast-enhancing mass with surrounding
edema, usually multiple
• Prognosis – poor, most die within a few months
54
PROSTATIC ADENOCARCINOMA
Patients usually present with spinal cord compression
Mets to vertebral bodies
55
* Benign tumor composed of Schwann cells
* Most common **4th to 6th** decades
* Involve peripheral nerves, usually in head and neck and flexor surfaces of
extremities
• Asymptomatic masses
• Spinal tumors–radicularpain
Schwannomas
56
• Intracranial tumors most often in cerebellopontine angle and attached to 8th
nerve
• Symptoms of hearing loss,tinnitis,facial numbness
• Scans show well-defined contrast enhancing mass
Schwannomas
57
Schwannomas are associated with
NFT2
58
See compact spindle cells or loose spongy areas and small cells with round nuclei
Schwannoma
59
General on Neurofibromas (Peripheral nerve sheath tumors)
Benign tumor composed of Schwann cells, fibroblasts, and perineural cells
Associated with **Neurofibromatosis type 1**
Multiple forms
* Cutaneous (localized) neurofibroma: most common • In dermis or subdermal
* Usually solitary (not associated with NF1)
• Peripheral nerve : Solitary or Plexiform - usually in NF1
60
On histology see shit that looks like shredded carrots with wavy nuclei, elongated spindle cells and hypocellular; diffusely infiltrative to adj nerve and soft tissue
Neurofibromas
61
Occurs almost exclusively in **NF1**
Transformation of multiple fascicles of nerves into this with preservation of anatomic configuration
Typically affects l**arger nerves or a plexus**
High likelihood of malignant transformation
Plexiform neurofibroma
62
* Mostly in extremities
* In CNS, assoc with trigeminal nerve
Strong assoc with NF1
High grade, aggressive
Infiltrative,non-encapsulated fleshy masses
• Highlycellular,moderateto marked nuclear pleomorphism
• High mitotic rate
Malignant peripheral nerve sheath tumor
63
More Familial Tumor Syndromes
* Each has cutaneous or eye abnormalities
* Old name is “Neurophakomatoses”
* Most are linked to loss of tumor suppressor genes
* Four types:
| (associated with increased risk of nervous system- associated tumors)
* Neurofibromatosis type 1
* Neurofibromatosis type 2
* Von Hippel-Lindau disease
* Tuberous sclerosis
64
**• Neurofibromas, café-au-lait spots, Lisch nodules, optic glioma, osseous lesions,**
**axillary freckling, family history **
* Autosomal dominant with Almost complete penetrance
* However, 50% represent new mutations
* 1: 3000 individuals (much more common than NF2)
Neurofibromatosis 1
| (von Recklinghausen disease)
65
Tumors associated with von Recklinghausen
• Neurofibromas (all types)
* Most important is neurofibromas that undergo transformation to malignant peripheral nerve sheath tumors
* Optic nerve gliomas and other astrocytomas
* Others (rhabdomyosarcomas, pheochromocytomas, carcinoid tumors)
66
Von Recklinghausen
## Footnote
NF1 gene on \_\_\_\_
• Gene product – \_\_\_\_\_\_
chr. 17
neurofibromin
67
Function of Neurofibromin seen in von Recklinghause
G-protein-dependent signal transduction pathway (at umor suppress or gene) that influences cell proliferation & differentiation
Abundant in Schwann cells and neurons
68
What are some give aways for neurofibromatosis 1
axillary freckling
cafe au lait spots
69
Optic nerve gangliomas and Lisch nodules are seen in:
This is in Neurofibromatosis or von Recklinghausen
Lische nodules
70
Criteria for NF2
Bilateral vestibular schwannomas (most common manifestation),f irst degree relative with NF2, lens opacity, cerebral calcifications
Other associated tumors: meningiomas, schwannomas, gliomas, neurofibromas
(Unlike NF1, **plexiform neurofibromas are not found** & malignant
transformation of neurofibromas is rare)
71
Genetics of NF2
\_\_\_\_\_\_ inheritance
gene\_\_\_\_ that makes \_\_\_\_\_
Auto D
gene 22
product is Merlin
72
What does 'merlin' (gene product of NF2)
**Tumor suppressor gene** which promotes assembly of cell junctions (with loss of gene, cell-to-cell contact is disrupted & this contributes to tumorigenesis)
73
Von Hippel Lindau disease
Pattern:
• Features:
Autosomal dominant
• Hemangioblastomas of CNS & retina and Cerebellar hemangioblastomas, renal cell carcinoma, pheocromocytoma, visceral cysts and retinal angiomas
74
VHL gene on chr. 3 is implictaed in what disease, what is it responsible for
Von Hippel Lindau disease
• VHL protein controls angiogenesis through regulation of expression of
endothelial growth factor, erythropoietin and other growth factors
75
Hemangioblastoma
Most commonly occurs in\_\_\_\_\_\_ and Occasionally in cerebrum or spinal cord
Symptoms usually secondary to \_\_\_\_\_\_\_\_\_\_due to obstruction
cerebellum
increased intracranial pressure
76
What does hemangioblastoma look like on MRI imaging?
Well defined contrst enhancing cystic mass with mural nodule
surgically resectable
77
Numerous vessels interspersed with stromal cells
Stromal cells have abundant **foamy cytoplasm** (contains fat)
Hemangioma!
78
Tuberous sclerosis
genetics:
* Autosomal dominant
* Positive family history in 50% • Occurs 1 in 6000
TS caused by mutations in 2 tumor suppressor genes
79
* TSC1 (chr. 9) – codes protein\_\_\_\_
* TSC2 (chr 16) – codes protein\_\_\_\_\_\_
IMplicated in tuberous slcerosis, what is their role
hamartin
tuberin
\*\*\* These proteins form dimers & regulate protein synthesis & cell proliferation (inhibit mTOR)
80
Devo of hamartomas and benign neoplasms: cortical hamartomas, subcortical glioneuronal, suependmal giant cell astrocytoma, cutansous angiobriomas, sub ungal fibromas, ect
all see in tuberal sclerosis
81
Tuberosclerosis stands for :HAMARTOMAS
Harmas in the CNS and skin
Angiofibomas
Mitral regurg
Ash leaf spts
cardiac Rhabdomyoma
Tubero sclerosis
dOminant
Mental retardation
Angiomulomas,
Seizures
Shagreen pathces
82
Neurons haphazardly arranged in cortex
Often have glial as well as neuronal features
Tuber histology
83
Most common primary brain tumor
meningiomas
followed by gliomas
84
Likely to cause obstructive hydrocephalus.. Exophytic solid well-defined mass arising
in the **wall of lateral ventricle**
Subependymal giant cell astrocytoma
85
Large pleomorphic multinucleated tumor cells with eosinophilic cytoplasm
May be of astrocytic or glioneuronal origin
No malignant transformation, local invasion reported
Subependymal giant cell turmo
86
A clinical syndrome produced by remote effect of a systemic malignancy that cannot be attributed to direct invasion by tumor or its metastasis, infection, ischemia, surgery, related metabolic or nutritional disorders or toxic effects of therapy
Paraneoplastic Syndromes
87
Most common associated malignancies with paraneoplastic syndromes
Most common associated malignancies • Small cell carcinoma
• Gynecologic malignancies
* Breast, ovary, fallopian tube, peritoneum • Hodgkin’s and non-Hodgkin’s lymphoma
* Testicular cancer
* Neuroblastoma
88
Two classes of paraneoplastic syndromes
1. Related to ectopic hormone production: ie. SIADH, ACTH
2. Neurologic syndromes: rare (0.1% or all cancer pts.; 3% of small cell lung cancer (SCLC) pts)
89
Most common neurologic syndomres, associated with strong FEMALEL predominance in paraneoplastic syndromes
2. Neurologic syndromes: rare (0.1% or all cancer pts.; 3% of small cell lung cancer (SCLC) pts)
* Strong female predominance
* Most common neurologic syndromes
* Subacute cerebellar ataxia • Limbic encephalitis
* Encephalomyelitis
* Opsoclonus myoclonus
* Subacute sensory neuronopathy
* Lambert-Eaton myasthenic syndrome
90
How do paraneopl. syndromes present
Subacute worsening over weeks to months
• May be presenting symptom of underlying malignancy
Initial cancer screening may be negative
Neuro symptoms occur when malignancy is at a limited stage due to effective anti-tumor immune response
Patientshavemorefavorableoncologicaloutcome
91
Pathogeneis for paraneoplastic syndromes
* Presumably induced against tumor cell antigens • Cross-reac twith neuronal cell antigens
* Pathogenesis
Hypothesized that some visceral cancers express certain neural antigens; immune system recognizes these antigens as foreign and mounts an immune response against them
Antibodies identified in some paraneoplastic syndromes
92
* Progressive ataxia, dysarthria, nystagmus, vertigo, diplopia, titubation
* Associated with ovarian cancer (80%) or breast cancer (10%)
* Antibody to Purkinje cells
* Purkinje cell antibody type-1 (PCA-1 or anti-Yo)
Subacute cerebellar ataxia: symptom of paraneoplastic syndrome
93
• Clinical: muscle weakness, especially in the legs, that improves with testing on exam
* Extraocular muscles are spared
* Antibodies to P/Q-type voltage-gated calcium channels
• Leads to decreased acetylcholine release • Most commonly associated with SCLC
Lambert Eaton Myasthenic Syndrome
94
Embryonal epitheilium, in posterior fossa with primitive neuroectoderm neoplasm
S/S ataxia and increased intracranial pressure. Drop mets
meduloblastoma
