28 . Tumors Flashcards
1
Q
Generally, how do metastatic tumors present in the CNS?
A
- Multiple, well-circumscribed lesions, most often at the grey-white junction.
- Top 3 metastic cancers are: lung, breast and kidney cancers.
2
Q
Generally, do primary malignant tumors of the CNS metastasize?
A
- No, they are locally destructive.
- Rarely metastasize.
3
Q
What are the key cells in the brain that produce tumors?
A
- Glial cells (astrocytes, oligodendrocytes, ependymal cells); 50%= supports and surrounds neurons
- Neurons (50%)
- Meningothelial cells = surround brain
4
Q
Astrocytes produce what tumors in kids and adults
A
- Kids = Pilocytic astrocytoma
- Adults = Glioblastoma (MC CNS tumor in adults)
5
Q
Oligodendrocytes produce what tumors and in who are they MC in
A
Oligodendromas = adults
6
Q
Ependymal cells produce what tumors and in who are they MC in
A
Ependymomas = children
7
Q
Neurons produce what tumors and in who are they MC in
A
Medulloblastomas (from neuroectoderm) = children
8
Q
Meningothelial cells produce what tumors and in whome?
A
Meningioma = adult females
9
Q
Where are brain tumors most common in kids and adults?
A
- Kids => infratentorial (posterior fosssa): cerebelleum & brainstem
- Adults => supratentorial (above tentorium)
10
Q
What are the MC brain tumors in children?
A
MC infratentorial
- Astrocytoma
- Medulloblastoma
- Ependymoma
- Craniopharyngioma
11
Q
What are the MC brain tumors in adults?
A
MC supratentorial
- Glioblastoma **
- Meningioma
- Schwannoma
- Oligodendroma
- Hemangioblastoma
- Pituitary Adenoma
12
Q
If you have a new onset of a seizure in a adult, think ________.
A
Brain tumor
13
Q
Which grade of tumor is considered infiltrative?
A
Grade II
14
Q
In which decade of life are Grade II, III, and IV Astrocytomas found?
A
- Grade II: usually 30-40s
- Grade III: usually 50s
- Grade IV: usually 60s +
15
Q
What are gliomas?
A
MC group of primary brain tumors: astrocytomas, oligodendrogliomas, ependymomas
16
Q
Pattern of growth and spread in tumors in CSF
A
- Most infiltrate extenselively, even if benign, displaying malignant behavior
- Spread via CSF, but even most malignant gliomas RARELY metastasize ouside CSF
17
Q
What are Pilocytic Astrocytomas?
- Usually occur when?
- Where in the brain do they typically occur?
A
Low-grade benign tumor of astrocytes that are the MC brain tumor in chidren; slow growing and prognostically favorable
- 0-20 (First 2 decades)
- Cerebellum, floor/walls of 3rd ventricles, between hemispheres
18
Q
What grade of tumor is a Pilocytic Astrocytoma?
A
Benign I/IV; they commonly extend into subarachnoid space, but not sign of aggression and optic nerve lesions
19
Q
What are the distinguishing morphological characteristics of Pilocytic Astrocytomas?
A
- Well-circumscribed, CYSTIC tumors w/ a mural nodule
- - Biphasic pattern: loose glial cells w cystic changes and dense piloid tissue
- Low cellularity
- - Hair-like cells w/ long bipolar processes
- - Rosenthal fibers = long-standing gliosis
- - Eosinophilic granular bodies (EGBs)
20
Q
Marker of Pilocytic astronoma
A
GFAP
21
Q
what do these findings signify in pilocytic astronomas?
A
- EGB = PAS + protein drops that mark a slow growing, low grade tumor that is prognostically favorable
- Rosenthal fibers = long standing gliosis
22
Q
Which disease predisposes patients to Pilocytic Astrocytomas and due to what?
A
NF-1 (neurofibromatosis 1) due to functional loss of neurofibromin
23
Q
Most common presenting signs and symptoms of Infiltrating Astrocytomas?
A
- Seizures
- HA
- Focal neurologic deficits
related to the site of involvement
24
Q
Infiltrating astrocytoma range from what kind of tumors?
A
- Grade II/IV: Diffuse astrocytoma
- Grade III/IV: Anaplastic astrocytoma
- Grade IV/IV: Glioblastoma (this is malignant)
25
Among the **higher grade astrocytomas,** presence of what mutation is associated with a **better outcome?**
**Mutant** form of **IDH1**
26
What are **Glioblastomas**?
**Most common primary brain tumor;**
Rapidly progressive, Grade 4 malignant tumor of astrocytes the in the **_cerebral hemispheres_**.
27
Where are **Glioblastomas** located?
**Cerebral hemispheres:** often cross the corpus callosum and form _"butterfly gliomas",_ which are _necrotic_ and _hemorrhagic_
28
Are **glioblastoma** primary tumors or secondary?
1. **Primary**: new tumor in older people
2. **Secondary**: progress in younger patients from a lower-grade astronoma.
29
What **mutations** are associated with **primary** and **secondary Glioblastomas?**
* **Primary _Glioblastomas (_**new tumor that occur in later people):
* _EGFR_
* _PTEN_
* **Secondary _Glioblastomas (_**proceeds from a lower grade tumor in younger patients):
* _TP53_
* _IDH1_ / _IDH2_
* (_R132H_ = better prognosis)
30
What mutation causing _secondary_ **Glioblastomas** are associated with a **BETTER prognosis?**
**R132H**
31
**_Glioblastomas_**
1. Histological pattern (3)
1. **Serpentine** pattern of necrosis
2. **Pseudo-palisading:** ⬆︎ in # tumor cells around necrosis
3. **Vascular/endothelial proflieration** that fill vascular lumen, producing a glomeruloid body (ball-like structure) due to ⬆︎ VEGF made by malignant astrocytes
32
**Ring-enhancing lesion** on MRI =\> think \_\_\_\_\_\_
**Glioblastoma:** ring enhancing lesions iwth hypodense central necrosis
33
Which tumor often **crosses the corpus callosum** and produces a **"butterfly" appearance of hemorrhage and necrosis?**
**Glioblastoma**
34
Which brain tumor appears as a **cystic mass** with a **mural nodule?**
**Pilocytic astronoma**
35
When are **Oligodendrogliomas** most commonly seen (decades)?
How are they graded?
* _Malignant_ tumor in oligodendrocytes that produces a _calcified tumor_ in _white matter,_ usually in the _frontal lobe._
* **Adults 40-50 YO**
* **Grade II/IV**
36
Where in the brain are **Oligodendrogliomas** most often seen?
**White matter** of **cerebral hemispheres (frontal CTX)**
37
What are the _most common mutations_ seen in **Oligodendrogliomas**; which have a better prognosis?
1. **IDH1** and **IDH2** (better prognosis) = MC
2. **Loss of 1p19q** (favorable prognosis)
3. **CDKN2A**
38
What are the distinguishing gross/histo morphological characteristics of **Oligodendrogliomas**?
1. Gross Morphology:
1. **White matter** TUMOR!!!
2. **Well circumscribed,** gelatin, grey, **_CYSTIC_** and **focal hemorrhage**
3. **CALCIFICATION** in the **CTX** (curvilinear or gyriform distribution)
2. Histology:
1. **Perinuclear halos** =\> creating "**fried eggs"** apperance (Artifact)
2. **Chicken wire vascular pattern:** delicate anastomosing capillaries
39
Which features distinguish an **Anaplastic Oligodendroglioma (III/IV)** from an **Oligodendroglioma**?
1. Vascular hypertrophy and necrosis, but keeps geometric vascularity
2. Nuclear anaplasia
3. Poor prognosis
40
What are **ependymoma** tumors?
Grade II/IV **malignant** tumors of ependymal cells, MC in **children** (first 2 decades of life = 0-20 YO)
41
What are the MC sites/ situations for **Ependymoma**?
1. **Children** = 4th ventricle =\> hydrocephalus
2. **Adults** = SC central canal
3. **Neurofibromatosis 2,** where NF2 gene is located
42
When **Ependymomas** occurs in adults they are most often associated with what other condition; due to what mutation?
**Neurofibromatosis 2** -- due to mutation of NF2 gene on **Chr22**
43
**Well circumscribed** tumors in the brain that often have **cysts**, **focal hemorrhage,** and **calcification** generally describes?
**Oligodendrogliomas**
44
**Histology** of **Ependymoma**
1. Uniform cells with **round-oval nuclei** and alot of **clumped chromatin**
2. **Epyndemal (true rosettes** = tubular structure w central canal**)** or **perivascular rosettes (**ependymal cells project processes towards central BV)
1. Ependymal are more diagnositc
45
Which rosette type found in **ependymomas** are more diagnostic?
**Ependymal rosettes (true rosettes)**
46
How do **Grade III/IV Ependymomas** present differently?
1. **Greater cell density and mitosis**
2. **Microvascular proliferation**
3. **Necrosis**
4. **Clear cell variane**
47
Which tumors are the following Rosettes MC in?
1. **HW (neuropil in middle):** _medulloblastoma_, neuroblastoma, PNET
2. **Flexner (true = lumen in center):** _ependymoma_, retinoblastoma, Wilms
3. **Pseudo (vessel in center):** _astroblastoma_ and thymoma
48
What is a frequent clinical manifestation of **posterior fossa ependymomas?**
**Hydrocephalus (non-communicating)** due to progressive obstruction of the 4th ventricle
49
Which location of **ependymomas** have the **worst** overall **prognosis** in **children**?
**- Posteior fossa** = worst overall prognosis; 5 year survival is 50%
- Completely resected supratentorial and spinal types are bette
50
**Choroid plexus papillomas** (increase CSF) are most often found where in _children_ and _adults_?
1. **Children** -- lateral ventricles
2. **Adults** -- 4th ventricle
51
Clinical symptoms of a **Choroid Plexus Papillomas**
**Obstuctrive hydrocephalus: make CSF**
52
Who is most often affected by _Non-neoplastic_ **Colloid Cysts** of the **3rd Ventricle?**
1. Located?
2. What is the clinical manifestation?
1. - **Young adults**
2. - Attached to roof of 3rd ventricle, can obstruct foramina of Monro =\> **non-communicating hydrocephalus**
3. - **HA** (can be positional; worse when standinging) =\> **rapidly fatal**
53
What is the most common **malignant embryonal** CNS tumor in _children_?
**Medulloblastoma (Grade IV/IV)** = poorly differentiated _neuroectodermal_ tumor that ONLY occurs _midline in the_ _cerebellum_
54
What are **medulloblastomas**?
_Malignant_, poorly-differentiated _PNET (peripheral neuroectodermal tumor)_ brain tumor, usually in **children**, that grows in the **MIDLINE cerebellum** =\> causing **truncal ataxia.**
In adults =\> grows more laterally
55
**Medulloblastomas** are often located where?
**Chilren; Midline** of the vermis of the cerebellum =\> truncal ataxia
Adults = more lateral hemispheres
56
**Medulloblastomas** can be divided into what 4 genetic groups?
Which have the best and worse prognosis?
1. **WNT mutation =** best prognosis
2. **SHH mutation**
3. **Group 3 =** worst prognosis
4. **Group 4**
57
1. **Medulloblastomas** that occur in **older children** tend to have what _mutations_ and _features_?
2. Prognosis?
Mutations in **WNT** signaling pathway
1. Only have one **Chr 6**
2. Nuclear expression of **β-catenin**
**Best prognosis (90% 5 year survival)**
58
1. **Medulloblastomas** due to mutations in **SHH signaling:** MC in who and associated with what other features?
2. **Prognosis**?
1. **Infants - young adults**
2. Mutations in SHH sigaling + **MYCN amplification**
3. **2nd best prognosis**
59
* **Group 3 medulloblastomas:** MC in who and associated with what other features?
* Prognosis?
1. **Infants** and **young children**
2. **MYC amplification** + **isochromosome 17 (i17q)**
3. **Worst prognosis**
60
**Group 4 medulloblastomas:** MC in who and associated with what other features?
Prognosis?
* **Isochromosome 17 (i17q)** + **without MYC** (but does happen sometimes)
* **Intermediate prognosis;** in general 17q = worse prognosis
61
**Gross Morphology** of Medulloblastomas
1. **Well-circumscribed;** _solid_ **gray, friable**
62
**Histology** of Medulloblastomas
1. **Sheets of anaplastic cells:** hyperchromatic nuclei and abundant mitoses
2. **Homer-Wright Rosettes:** small round blue cells around neuropil
63
**Clinical features/complications** of Medulloblastomas
1. Poor prognosis: Grow fast =\> **NTRS 4th ventricle and occlude CSF** =\> **hydrocephalus**.
2. Spread from CSF =\> form masses far away, like cauda equina SC **(drop metases)**
3. Infiltrate **cerebral CTX** and penetrate the **pia** =\> **subarachnoid space**
64
Marker for Medulloblastoma
**GFAP +**
65
What is a common complication due to **Medulloblastomas** propensity to **form linear chains** and **infiltrate?**
Infiltrate **cerebral CTX** and penetrate the **pia** =\> **subarachnoid space**
**Dissemination through CSF** is common complication, =\> nodular masses some distance from the priamry tumor (i.e., as far as the cauda equina) -- Drop Metastases
66
How well do **Medulloblastomas** respond to treatment?
**- VERY radiosensitive**
- Total excision and irradiation =\> **5 year survival of 75%**
67
What is a **CNS supratentorial PNET**?
**Primitive neuroectodermal tumor**
68
What is the difference between how **Pilocytic Astronomas** and **Medulloblastomas** look?
* **Medulloblastomas**: well-circumscribed, solid, grey and friable; VERY cellular
* **Pilocytic astrocytomas:** cystic, biphasic architecture and low cellularity
69
What is the difference between **Ependymoma** and **Medulloblastomas** look?
**Ependymoma =**
1. perivascular pseudorosettes
2. less cellular
3. more fibrillar
70
Differentiate metastic carcinoma with Medulloblastomas?
* Metastatic cancers are MC in adults
71
Differentiate **High-Grade Infiltrating Astrocytomas** with **Medulloblastomas**
**More pleiomorphic**
72
What are A**typical Teratoid/Rhabdoid Tumors (AR/RT)**
* MC in whom
* Where are they seen in the brain?
* Benign or malignant?
- Very **malignant** (grade _IV_) tumor in **young children (\< 5 YO**)
- **Posterior fossa** and **supratentorial compartments**
73
Mutations in **AT/RT?**
**Chr 22 deletion**, specially the **HSNF5/INI1**
74
**Cytoplasm** of **rhaboid cells** found in Rhaboid tumors is immunoreactive for what?
1. **Epithelial membrane antigen (EMA)**
2. **Vimentin**
3. \*Other markers may include: **smooth muscle actin** and **keratins; NO desmin and myoglobin**
75
**Histology** of AT/RT (Atypical Teratoid/Rhaboid Tumor)
* **Rhabdoid cells:** eosinophilic cytoplasm with sharp borders & eccentric nucleus, resemble rhabdomyosarcoma
76
Prognosis of **AT/RT**
**Very aggressive,** less than 1 yr survical
77
What is the **most common CNS neoplasm** in _immunosuppressed patients_, such as those with _AIDS_ or following transplantation?
**Primary CNS lymphoma**
78
Most **primary CNS lymphomas** are of \_\_\_\_\_origin (immune cell) and latently infected by _____ virus
**B-cell CD20+**
**EBV**
79
* What is the **morphology** of the lesions associated with **Primary CNS Lymphomas?**
* **how do they spread?**
* Which stain shows their characteristic pattern?
1. **Many lesions** (multifocal) in **grey** and **white matter**; rarely outside CNS
2. Infiltrate parenchyma and accumulate around vessels
3. **Periventricular** spread
4. **Stain**: _Reticulin_ + _silver stain:_ "_hooping_" = infiltrating cells seprated from one another by silver strain
80
_**Germ Cell Tumors** in the brain_
1. Occur where?
2. MC in who?
* Occur along the **midline**, most commonly in the **pineal gland (M)** and **suprasellar regions.**
* **Japanese M 0-20**
81
Which **markers** of CNS **germ cell tumors** may be helpful in assisting with diagnosis and tracking response to therapy?
1. **- α-fetoprotein**
2. **- β- hCG**
82
**Metastasis** of which type of germ cell tumor to the **CNS** is common?
What is the significance of this in regards to classifying the tumor?
**Gonadal germ cell tumors,** thus, we have to _rule out_ a _non-CNS primary tumor_ before we exclude diagnosis of a primary germ cell tumor
83
The tumor that is histologically similar to a **seminoma** **in the** **testis** is reffered to what in the CNS?
**Germinoma**
84
What is the response of primary brain **germ cell tumors** to radiation therapy/chemotherapy?
**Good response**
85
**Pineal parenchymal tumors** are derived from pineocytes;
What type do we see in the brain?
**Well-differented lesions** with **neuronal differentiation** (**pinocytomas**)
=\>
**high-grade tumors** (**pineoblastomas**)
that spread throughout the **CSF**.
86
* **High-grade pineal tumors** (\_\_\_\_\_\_\_\_) are MC in \_\_\_\_\_\_\_\_
* **Low-grade pineal tumors** (\_\_\_\_\_\_\_\_) are MC in \_\_\_\_\_\_\_\_
* **High-grade pineal tumors** (_pineblastoma_) are MC in **kids**
* **Low-grade pineal tumors** (_pinecytoma_ = neuronal differentiation) are MC in adults
87
**Pineblastomas** are high-grade pineal tumors w/ _necrosis_ and _mitosis_ that are MC in kids.
What is the _mutation_?
**RB gene**; spreads throughout CNS
88
What is the **most common _pineal tumor_?**
**Germinoma**
89
What are **meningiomas**?
* **Grade I/IV**
* **MC benign** **tumors in adults** (F \>30YO) of **arachnoid meningothelial cells (EMA +)** and are **attached to the dura,** _penetrating bone_ and _compressing brain (do NOT infiltrate brain)_ =\> can cause _seizures_
90
How do **Meningiomas** grow?
* **Enlarge slowly**
* **DONT infiltrate** brain.
* But, they **compress** it and the **penetrate the bone.**
91
What is a risk factor for the development of **Meningiomas**?
Prior **radiation** to the **head** and **neck**, typically decades earlier
92
What is the severity of **Meningiomas**, who are they commonly seen in and where are they found?
1. - **Benign** tumors of adults **(\>30 F)**
2. - Usually attached to the **dura**; found along any of the **external surfaces of the brain** as well as ventricular system
93
What is the most common cytogenic abnormality seen in **Meningiomas**?
- Loss of **Chr 22,** especially the long arm **(22q)**, which has the **NF2 gene**, that encodes **merlin.**
## Footnote
**= \> seend more often in NF2**
94
**Higher-grade Meningiomas** are associated with what mutations?
1. NF2 mutations,
2. loss of chromosome 22
3. **Chromosomal instability \*\***
95
What is the most common mutation seen in **Meningiomas without NF2 mutations?**
What is the histologic grade of this type?
1. **TNF-receptor associated 7 (TRAF7)**
2. **Lower histologic grade**
96
Gross morphology of **Meningiomas**
1. **_Solitary_, round/bossilated** (looks like BLACKBERRIES) **tumor** with attached to dura that **compress underlying brain,** but **easily separate** from it.
1. if many = think _NF2_
2. **Firm**, _no_ necrosis or extensive hemorrhage
3. **Calcified psammoma bodies**
4. **En plaque:** tumor has a sheet-like spread along the surface of the dura
97
**Histology** of Meningiomas
**Various histological patterns, with no prognostic significance.**
1. Syncytial
2. Fibroblastic
3. Transitional
4. Psamomatous
5. Secretory
6. Microcystic
1. **Wholed clusters of monotonous cells**
2. **Calcified psammoma bodies**
3. **EMA +**
98
Which subtype of **Meningiomas** has _PAS+ intracytoplasmic droplets?_
Is associated with mutations in what genes?
* - **Secretory** subtype
* - **TRAF7** and **KLF4** genes
99
What is the typical patient presentation for a **Meningioma**?
Present with **vague** **non-localizing signs** and symptoms or with **focal findings** due to **compression of underlying brain**
100
Which receptors may be expressed by **Meningiomas** and which patient population can this potentially affect?
- **Progesterone (70% have)** and **Estrogen (31%) receptors,** thus, more common in F
- **Pregnancy** increases ⬆︎**symptoms, NOT incidence**
101
If a patient has multiple meningiomas, what should we think of as the cause?
**Neurofibromatosis 2**
102
Metastatic carcinomas are the MC metastatic brain tumo. They account for 1/2 of the intracranial tumors in hospitilized patients.
Where is the **MC primary sites** for **potential metastasis** to the brain?
* 1. Lung (35%)
* 2. Breast
* 3. Skin (melanoma)
* 4. Kidney
* 5. GI
103
Which **rare** tumor has a **high** likelihood of metastasing to the brain?
**Choriocarcinomas**
104
Which **common** tumor, but **RARELY** metastasizes to the brain?
**Prostate**
105
Where in the CNS is a **frequent site** of involvement for metastatic disease?
1. **- _Meninges_**
2. **- Intraparenchymal = _Gray/White junction_**
106
**Meningeal carcinomatosis** (tumor nodules along the surface of the brain, SC and intradural nerve roots) most commoly occurs with which _carcinomas_?
1. **Lung**
2. **Breast**
107
What are the common histologic findings of **metastases** to the **CNS**?
**Nodules** of tumor, often with **central areas of necrosis**, surrounded by **reactive gliosis**
108
What are **paraneoplastic syndromes?**
Result from **malignancy** **elsewhere** in the **body** and are mostly due to **anti-tumor immune responses** that cross react with **central/peripheral NS antigens.**
109
* What is s**ubacute cerebellar degeneration** (paraneoplastic syndrome)?
* Due to?
* Common in which _cancers_?
* **PCA-1 AB (anti-Yo)** destrory _purkinje cells_, cause _gliosis_, and a _mild chronic inflammatory cell infiltrate_
* Commonly seen in
1. Ovarian
2. Uterine,
3. Breast cancer
110
**Small cell lung carcinoma** =\> cause **limbic encephalitis (paraneoplastic)** due to what AB?
**ANNA-1 antibody (anti-Hu)** recognized neuronal nuclei in the CNS and PNS
111
**Ovarian teratomas** =\> can cause **limbic encephalitis (**paraneoplastic syndrome = subacute dementia associated with perivascular inflammation, microglial nodules, neuron loss and gliosis MC in anterior and medial temporal lobe) due to what AB?
**NMDA-receptor AB** attack **neurons in** **hippocampus**
112
Which antibody is most commonly associated with **peripheral neuropathy** and may cause **limbic encephalitis (paraneoplastic)?**
**VGKC-complex AB:** voltage-gated potassium channel
113
What is an important consideration in regards to **limbic encephalitis** and **malignancy**?
The **syndrome** **appears before any malignancy** is suspected
114
**What is a paraneoplastic syndrome** commonly caused by **Neuroblastomas, in kids?**
**Opsoclonus (eye movement disorder)**
115
**Lambert-Eaton myasthenic syndrome** is caused by _antibodies_ against?
**(VGCa2+ channels)** in the presynaptic neurons
116
**Treatment** of paraneoplastic syndroemes
**Immunotherapy** to remove circulating Ab and **remove tumor**
117
**Germ cell tumors** are commonly located _midline_, at the pineal gland or suprasellar region.
What is the MC tumor of the **pineal gland?**
**Germinoma**, a GERM CELL tumor, not a pineocyte-derived tumor.
118
F patient undergoes **EXTENSIVE radiation.** What brain tumor is she most likely to get?
**Meningioma**; often caused by radiation.
119
Patient has a choriocarcinoma. What is the 1st step in imaging?
Typically goes to **brain**: make sure it didnt go there.
120
Which metastatic carcinomas to the brain often hemorrhage?
* **1. Melanoma**
* **2. Choriocarcinomas**
* **3. Renal cell carcinoma**
121
What familial syndromes cause **pheochromacytomas**?
1. **MEN2A/B**
2. **NF1**
3. **VHL (Von-Hippel Lindau syndrome)**
122
**_Cowden Syndrome_**
* Inheritance
* Chromosome
* Gene/Protein
* NL function/manifestation of loss
* Inheritance = **AD**
* Chromosome= **10q23**
* Gene/Protein= **PTEN/PTEN =\> IK3/AKT signaling**
* NL function/manifestation of loss = **lipid phosphatase** /
1. gangliocytoma tumors
2. benign follicular appendages (trichelemmomas);
3. internal adenocarcinoma (breast or endometrial)
123
**_NF1_**
1. Inheritance
2. Chromosome
3. Gene/Protein
4. NL function/manifestation of loss
1. AD
2. 17q11
3. NF1/neurofibromin
4. (-) regulates RAS signaling / neurofibromas
124
**_NF2_**
1. Inheritance
2. Chromosome
3. Gene/Protein
4. NL function/manifestation of loss
1. AD
2. 22q12
3. NF2/merlin
4. Cytoskeleton signaling/ neurofibromas and acoustic neuromas
125
**_Tuberous Sclerosis_**
1. Inheritance
2. Chromosome
3. Gene/Protein
4. NL function/manifestation of loss
1. AD
2. 9q34 and 16p13
3. TSC1/hamartin and TSC2/tuberin
4. TSC1 and TSC2 form a complex =\> negatively regulate mTOR/ angiofibromas and mental retardation
126
**Li-Fraumeni syndrome** is caused by a mutation of ____ =\> what tumor?
**TP53 =\> medulloblastomas**
127
**Turcot syndrome** is caused by a mutation of ____ =\> what tumor?
1. **APC** or **mismatch repair genes**
2. **Medulloblastomas** or **glioblastomas**
128
**Gorlin syndrome** is caused by a mutation of ____ =\> causes what tumor?
1. **PTCH mutation** =\> upregulation of SHH pathway
2. **Medulloblastoma**
129
**Tuberous Sclerosis Complex** is characterized by the development of what?
Most frequent clinical manifestations are?
- Development of benign **hamartomas** & **benign neoplasms** in brain and other tissues:
1. Cortical tubers (=\> cause seizures),
2. Subependymal nodules
3. Renal angiomyolipomas
4. Cardiac rhadomyomas
5. Shagreen patches (local thickening of skin)
6. Ash-leaf patches (hypopigmented areas)
130
Which tumors are associated with the **Tuberous Sclerosis Complex?**
1. Cardiac rhabdomyoma
2. Renal angiomyolipomas
3. Cortical tubers
4. Giant cell astrocytomas
131
What are the **cutaneous lesions** associated with the **Tuberous Sclerosis Complex?**
1. **Shagreen patches** (localized cutaneous thickenings)
2. **Ash-leaf patches (**hypopigmented areas)
132
Tuberous sclerosis causes multiple small tumor that are described as what?
Candle guttering: drop like masses that bulge into ventricles
133
**_Von Hippel-Lindau disease_**
* Inheritance
* Chromosome
* Gene
* What is the function of the protein associated with this gene?
* AD
* Chr 3p25.3
* VHL tumor supressor
* **VHL** =\> ↓ regulates **HIF1** =\> _regulates_ expression of **VEGF =\>** regulates **erythropoeitin**
134
**VHL Disease** causes what?
1. **Polycythemia** due to ⬆︎ VEGF =\> erythropoeitin
2. **Hemangioblastomas** in cerebellum and retina
3. **Pheochromacytomas** - in adrenal gland
4. **Cysts** in [pancreas, liver, kidneys]
5. **Renal cell carcinoma**
135
What is the mnemonic using **VHL** for Von Hippel-Lindau Disease?
* - V = VHL gene
* - H = Hemangioblastoma (cerebellum and retina)
* - L = Lots of catecholamines = pheochromocytoma
* \*VHL = 3 letters = RCC (renal cell carcinoma)
* \*VHL = 3 letters = Chr 3
136
**NF1** is more common and is characterized by which malignancies and other findings?
1. **Neurofibromas** in peripheral nerve
2. **Optic nerve gliomas**
3. **Lisch nodules:** pigmented nodules of the iris
4. **Cafe au lait spots:** cutaneous hyperpigmented macules
137
**NF2** is most commonly characterized by which malignancies?
1. **Bilateral schwannomas of CN VIII**
2. Multiple **meningiomas** and **ependymomas** of **SC**
138
What are **peripheral nerve sheath tumors?**
1. **Schwannoma**
2. **Neurofibromas**
3. **MPNST**
139
**_Schwannomas_**
1. Marker
2. MC occur?
3. Mutation:
4. Histology
1. **S100**+
2. Cerebellar pontine angle =\> acoustic neuromas of CN8 (=\> tinnitus and hearing loss)
3. NF2 =\> loss of merlin
4. Histology
1. **Antoni A bodies** (spindle cells with nuclei aligned in palisading rows, leaving nuclear free zone and forming verocay bodies)
2. **Antoni B bodies** = ECM with no cells
140
Which type of neurofibromas look like a **bag of worms** and often have **malignant transformation** into **MPNST**?
**Plexiform neurofibromas**
141
What are **MPNST**?
Who do we comonly see them in?
85% are high-grade tumors, with 1/2 arising in pts w **NF1**.
