Neurosurgery: Neoplastic Disease

Question 1

Approach to:

Inferior frontal lobe and parasellar region

Answer 1

Bicoronal incision with unilateral/bilateral subfrontal approach
Pterional approach

Question 2

Approach to:

Sellar region

Answer 2

Transsphenoidal
Bicoronal incision with unilateral/bilateral subfrontal approach
Pterional approach

Question 3

Approach to:

Frontal lobe

Answer 3

Frontal craniotomy (linear, curved, or horseshoe incision)

Question 4

Approach to:

Anterior temporal lobe

Answer 4

Temporal craniotomy (linear incision)

Question 5

Approach to:

Posterior temporal lobe

Answer 5

Temporal craniotomy (linear, reverse question mark, or Isle of Mann incision)

Question 6

Approach to:

Parietal lobe

Answer 6

Parietal craniotomy (linear or horseshoe incision)

Question 7

Approach to:

Occipital lobe

Answer 7

Occipital craniotomy (linear or horseshoe incision)

Question 8

Approach to:

Trigone of lateral ventricle

Answer 8

Appropriate craniotomy for superior parietal, middle temporal gyrus, lateral tempero-occipital, or transoccipital approach (linear or horseshoe incision)

Question 9

Approach to:

Anterior third ventricle

Answer 9

Frontal parasagittal craniotomy and interhemispheric/transcallosal or transcortical approach

Interforniceal or transchoroidal approach once within

Question 10

Approach to:

Posterior third ventricle/pineal region

Answer 10

Suboccipital transtentorial
Supracerebellar infratentorial approach
Interhemispheric transcallosal (splenium) approach
Transcortical parietal approach (rarely used)

Question 11

Approach to:

Midline posterior fossa/fourth ventricle

Answer 11

Suboccipital craniotomy (linear incision)

Question 12

Approach to:

Lateral posterior fossa/CPA

Answer 12

Retrosigmoid craniotomy (linear incision)

Question 13

Approach to:

Upper clivus

Answer 13

Subtemporal approach and anterior petrosectomy (linear or horseshoe approach)

Question 14

Approach to:

Middle and lower clivus

Answer 14

Combined retrosigmoid posterior temporal craniotomy and posterior petrosectomy (curvilinear incision)

Question 15

What is located two finger breadths above the zygomatic arch and one thumb’s breadth behind the frontal process of zygomatic bone?

Answer 15

Pterion

Question 16

What landmark does the asterion represent?

Answer 16

Asterion is on skull over the lower half of the transverse/sigmoid sinus junction

Asterion: junction of lamboid, occipitomastoid, and parietomastoid sutures

Question 17

What lays at the junction of the lamboid and sagittal suture?

Answer 17

Lambda

Question 18

What lays at the junction of the coronal and sagittal sutures?

Answer 18

Bregma

Question 19

Where is the inion located?

Answer 19

At indentation below external occipital protuberance

Question 20

How can you roughly estimate the location of the Sylvian fissure? (Stepwise approach)

Answer 20

1) Draw a line connecting the nasion and inion, find the 75% point on the line (closer to inion)
2) Mark frontozygomatic point
3) Connect the two points and the Sylvian fissure travels along this axis

• Pterion is located ~3cm behind the frontozygmatic point

Question 21

How can you approximate location of Rolandic fissure (aka central sulcus)? (Stepwise approach)

Answer 21

1) Find upper Rolandic point (2cm posterior from 50% point on a line connecting nasion and inion)
2) Lower Rolandic point is at junction of line from upper rolandic to midzygomatic arch and sylvian fissure line (Lower Rolandic point is 2.5 cm behind pterion along Sylvian line)

Question 22

How far behind the coronal suture is the motor stip usually located?

Answer 22

4 to 5.4 cm

Question 23

What is a rough estimate of the location of the Angular gyrus (which is part of Wernicke’s area)?

Answer 23

Just above pinna of ear

Question 24

Astrocytic tumors may be graded II, III, or IV. What are these specific types typically called?

Answer 24

Grade II: Low grade astrocytoma
Grade III: Anaplastic astrocytoma
Grade IV: GBM

Question 25

What is standard treatment for astrocytomas?

Answer 25

Surgical resection (partial or complete) followed by external beam radiation and temozolomide

Question 26

What are common locations for pilocytic astrocytomas?

Answer 26

Cerebellar Optic glioma type Hypothalamic hemisphere

Question 27

Optic gliomas are common in what genetic condition? | What type of tumors are these typically?

Answer 27

NF1 | Pilocytic astrocytomas

Question 28

What is tx of choice for cerebellar pilocytic astrocytomas?

Answer 28

Surgical resection They often have an enhancing mural nodule; if the mural nodule (contrast-enhancing) is removed the cyst wall doesn't need to be completely taken

Question 29

What is treatment of choice for pilocytic astrocytomas of optic nerve or hypothalamus?

Answer 29

If sparing resection can be completed then removal but if resection risky then biopsy with chemo and radiation

Question 30

How do oligodendrogliomas often present?

Answer 30

Seizures and/or hemorrhage

Question 31

What is unique about oligodendrogliomas on CTH?

Answer 31

They may have associated calcifcation

Question 32

What chromosomal loss is associated with better response to treatment in oligodendroglioma?

Answer 32

Loss of 1p and 19q

Question 33

Where do ependymomas often arise from?

Answer 33

Floor of 4th ventricle

Question 34

What is preferred treatment of ependymomas? | Should you aim for full resection?

Answer 34

Surgical resection | Maximal resection is associated with improved survival

Question 35

Given proximity to CSF space. What adjunctive test should be done in patients with ependymoma?

Answer 35

LP (cytology) and spinal MRI to look for subarachnoid mets

Question 36

In what age group do choroid plexus papillomas often present? How do they present? What is mgmt?

Answer 36

<2 yo HCP Resection followed by chemo (radiation if carcinoma)

Question 37

What are the different types of pediatric brainstem glioma (3)?

Answer 37

Tectal glioma Focal tegmental mesencephalic Diffuse pontine glioma

Question 38

What is general treatment of choice for each of following types of pediatric brainstem glioma: Tectal giioma Focal tegmental mesencephalic Diffuse pontine glioma

Answer 38

Tectal glioma: CSF diversion due to HCP risk Focal tegmental mesencephalic: Resection, chemo/rad Diffuse pontine glioma: radiation, experimental chemo, palliative

Question 39

Angiocentric glioma

Answer 39

Rare, slow-growing low-grade glial often in kids/young adults with seizures. Resection often curative

Question 40

Choroid glioma third ventricle

Answer 40

Rare low-grade glial often with HCP/chiasm compression/hypothalamic dysfunction often cured by resection

Question 41

Astroblastoma

Answer 41

Rare low-grade glial tumor often in kids/young adults and surgically resected with adjuvant chemo/rad

Question 42

What is dysplastic cerebellar gangliocytoma also known as? What syndrome is it associated with? How does it present and how is it managed?

Answer 42

Lhermitte-Duclos Disease Cowden Syndrome (multiple hamartomas) Inc'd ICP/HCP, cerebellar signs, slow progression Resection

Question 43

Desmoplastic infantile ganglioglioma presents in what age group? How does it present? What is it's survivability? What is optimum treatment?

Answer 43

<2 yo (peak 3-6 months) Bulging fontanelles, inc'd head size, paresis, seizures >75% survive at 15 years Resection curative; chemo if anaplasia

Question 44

In what age group do dysembryonic neuroepithelial tumors (DNETs) present? Are they fast or slow growing lesions? What will they commonly present with? What is treatment?

Answer 44

Children and young adults (<20 yo) Slow growing, benign Epilepsy Surgical resection +/- epileptogenic foci

Question 45

In what age group do gangliogliomas/gangliocytomas present? What is typical presentation? What is mgmt?

Answer 45

<30 yo (peak 11 yo) Epilepsy; slow growing, benign lesions Resection +/- chemo if anaplastic

Question 46

In what location do central neurocytomas often present? What is presentation? What is survivability? What is mgmt?

Answer 46

Intraventricular ICP rise and HCP; seizures 5 yr survival > 80%; benign and slow-growing Resection; SRS/chemo for recurrence

Question 47

Central liponeurocytoma often presents in what age group and what location? What is appropriate management?

Answer 47

Adults; posterior fossa | Resection; possible radiation to prevent recurrence

Question 48

How common is papillary glioneuronal tumor? What is presentation? What is mgmt?

Answer 48

Rare adult tumor Seizures; slow-growing, benign tumors Resection

Question 49

How do rosette-forming glioneuronal tumors of the 4th ventricle often present? What is mgmt?

Answer 49

Rising ICP and HCP with ataxia (In young adults often) Resection usually curative

Question 50

Paraganglioma at the carotid bifurcation is known as ...

Answer 50

Carotid body tumor

Question 51

Paraganglioma at the superior vagal ganglion is known as ...

Answer 51

Glomus jugulare tumor

Question 52

Paraganglioma at the auricular branch of vagus is known as ...

Answer 52

Glomus tympanicum

Question 53

Paraganglioma at the inferior vagal ganglion is known as ...

Answer 53

Glomus intravagale

Question 54

Paraganglioma of the adrenal medulla and sympathetic chain is known as ...

Answer 54

Pheoochromocytoma

Question 55

How rapidly do paragangliomas grow and what is appx 5 year survivability?

Answer 55

Slow; 90%

Question 56

How are paragangliomas managed?

Answer 56

If catecholamine secreting (i.e. pheochromocytoma) then alpha and beta blockers to prevent BP lability and arrhythmias Resection; radiation is nonresectable Preop embolization can reduce blood loss

Question 57

``` What is the peak age incidence for pineocytomas? How do they present? What is survivability? What is treatment? What treatment is high risk? ```

Answer 57

``` 10-20 yo ICP issues; Parinaud's syndrome 90% at 5 years Resection SRS is a high risk procedure for these tumors ```

Question 58

What age group do pineoblastomas arise in? How do they present? What is survivability? What is treatment?

Answer 58

Peak incidence 2 yo ICP issues; Parinaud's syndrome Median survival 2 years Resection + chemo + rad if > 3 yo

Question 59

Why is pineoblastoma associated with worse survival than pineocytomas?

Answer 59

Pineoblastoma is a PNET type of tumor with associated CSF seeding in ~50% of patients

Question 60

What is appropriate treatment of a papillary tumor of the pineal region?

Answer 60

Surgical resection followed by radiation

Question 61

What is a key distinguishing feature of embryonal/primitive neuroectodermal tumors (PNETs) regarding their spread?

Answer 61

CSF seeding/dissemination in many patients

Question 62

What are types of PNET tumors?

Answer 62

Medulloblastomas CNS PNET/Supratentorial PNET ATRT Pineoblastomas

Question 63

At what age and at what location do medulloblastomas often present?

Answer 63

``` 5 years old median Posterior fossa (1/3) ```

Question 64

How quickly do medulloblastomas present and with what signs?

Answer 64

Rapidly | ICP rise, HCP, cerebellar signs

Question 65

If there is no metastasis and there is a gross total resection then what is the 5 yr survivability of medulloblastomas? (Hint: it depends on a genetic factor)

Answer 65

If ERBB-2 tumor protein negative then near 100% | If ERBB-2 tumor protein positive then 54%

Question 66

What is the 5 year survival of medulloblastomas which exhibit metastasis or if there is residual postresection?

Answer 66

~20%

Question 67

What are variants of CNS PNET tumors?

Answer 67

``` CNS neuroblastoma (including esthesioneuroblastoma) Ganglioneuroblastoma Medulloepithelioma Pineoblastoma Ependymoblastoma ```

Question 68

What is the appx 5 year survival of CNS PNET tumors? | What factors increase chances of survival?

Answer 68

~ 30% | Complete resection, no metastasis, age > 2, heavily calcified lesion

Question 69

What is appropriate treatment of CNS PNET tumors?

Answer 69

Aggressive surgical resection (since extent of resection impacts prognosis in most cases) + chemo + rads if > 3 yo

Question 70

At what age do atypical teratoid-rhabdoid tumors present? How do they present? What is prognosis? What is treatment?

Answer 70

< 3 yo ICP elevation, developmental regression, seizures, torticollis Median survival is 6 months Gross total resection

Question 71

How does the presentation of schwannoma differ based on age?

Answer 71

<30 yo more likely to be parnechymal with seizure/epilepsy presentation >30 yo more likely vestibular schwannoma with sensorineural hearing loss, tinnitus, and dizziness

Question 72

How often do schwannomas recur?

Answer 72

They're slow growing and only recur in ~ 10% of cases post-resection

Question 73

For schwannomas < 3cm in diameter what are options for management?

Answer 73

May follow symptoms, audiology, and scans every 6 month. SRS is an option for these. Surgery can also be an acceptable option but the risk of CN VII damage or hearing loss may be high relative to risk of the small lesion

Question 74

Approximately what is the chance of hearing preservation in removing a schwannoma > 3cm?

Answer 74

40% | Chances of hearing preservation decrease as the size of the tumor increases

Question 75

There are 4 approaches to consider for removing a vestibular schwannoma. What are they and which is best and worst for hearing preservation?

Answer 75

Translabyrinthine (sacrifices hearing but may better preserve CN VII) Suboccipital (may best preserve hearing) Retromastoid Subtemporal

Question 76

Neurofibromas (including the plexiform type) often arise from where? What condition are they associated with?

Answer 76

In the orbit (V1), scalp, parotid (CN VII) NF1

Question 77

Are neurofibromas fast or slow growing? | Do they recur often?

Answer 77

Slow growing but 2-12 % degenerate into malignant nerve sheath tumors Recurrence is high

Question 78

What is the main indication for surgical resection of neurofibromas? How likely is complete resection?

Answer 78

Neural compression | Complete resection nearly impossible

Question 79

What is a perineurioma?

Answer 79

Rare, slow-growing, benign lesions growing on perineurial cells often treated with surgical removal (may be plexiform)

Question 80

In cases of malignant peripheral nerve sheath tumors what adjunct to resection is there?

Answer 80

Chemo and radiation

Question 81

What are the two most important risk factors for recurrence of a meningioma? What is the 20 year rate of recurrence?

Answer 81

Atypical histology Extent of resection 20-50%

Question 82

Risk of meningiomas is higher in what condition?

Answer 82

NF

Question 83

What are examples of benign mesenchymal tumors and tumor-like lesions? Do these need to be resected?

Answer 83

Lipoma, angiolipoma, rhabdomyoma, chondroma, leiomyoma, osteochondroma, benign fibrous hisiocytoma, osteoma, solitary fibrous tumor, and hemangioma No. Sometimes they are for cosmetic reasons

Question 84

Unlike benign types, malignant mesenchymal tumors and tumor-like lesions often require resection. What are some types? What is median survival generally? (Hint: there is one exception, what is it?)

Answer 84

Rhabdomyosarcoma, chondrosarcoma, Ewing tumor, osteosarcoma, leiomyosarcoma, Kaposi sarcoma, liposarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant fibroid histiocytoma Aggressive and median survival 6-24 months Exception is hemangiopericytoma which is 80% at 5 years

Question 85

Hemangioblastoma is associated with what condition? Hemangioblastoma makes up ____ % of posterior fossa tumors

Answer 85

Von Hippel Lindau Syndrome 10%

Question 86

What is survivability of hemangioblastoma? | What is treatment?

Answer 86

85% at 10 years (slow growing) | Resection +/- preop embolization

Question 87

How are primary malignant melanomas of meninges treated? What is the prognosis?

Answer 87

Surgical resection with chemo and radiation | Poor prognosis

Question 88

What other operation may a patient with diffuse melanosis/meningeal melanomatosis require and why?

Answer 88

Shunt placement for HCP

Question 89

If a patient presents with primary CNS lymphoma and is 30 how will your management differ than if they were 60? What if they were 10?

Answer 89

The younger the patient the more likely an acquired or inherited immunodeficiency state. If 10 yo consider an inherited immunodeficiency, if 30 think acquired (e.g. AIDS)

Question 90

With what predominant symptom may primary CNS lymphomas often present?

Answer 90

Neuropsychiatric changes

Question 91

How does median survival in primary CNS lymphoma change depending on treatment?

Answer 91

1-4 months if left untreated | 1-4 years if treated

Question 92

What is the treatment for primary CNS lymphoma?

Answer 92

No surgery usually. High dose methotrexate for young patients Steroid response is helpful and dramatic but may be short-lived

Question 93

Where do plasmacytomas arise and why? | What is treatment and what must be ruled out and how?

Answer 93

Often skull due to plasma cells in marrow Complete surgical resection but need to rule out multiple myeloma with urine and serum protein electrophoresis. There is a high risk of developing multiple myeloma

Question 94

In what age group does granulocytic sarcoma arise and associated with what other malignancy? What is median survival? What is first line treatment?

Answer 94

Pediatrics, usually associated with AML 2-20 months median survival Chemo/Rad therapy first line; surgical resection reserved for emergent mass effect

Question 95

What are the 3 types pf astrocytes?

Answer 95

**Fibrillary** - in WM, PTAH, silver, GFAP pos. **Protoplasmic** - in GM, larger nucleous, less citoplasm **gemistocytic** - swollen, active, near injury

Question 96

Circumscribed astrocytic tumors

Answer 96

low gr, good prognosis, frequently cystic 1. Juvenile pilocytic astr. 2. pleomphic xantoastrocytoma 3. Subependimal gian cell astr.

Question 97

General attributes of pilocystic astrocytomas

Answer 97

2nd most common ped. brain tumor location: cerebellum, brainstem, optic pathway!, infundibulum age: 10 yrs morphology: red-tan nodule, 60% cystic, nodule enhance, 10% contain calcium survival: 5y: 86-100% 20y 70%

Question 98

Histology of pilocystic astrocytomas

Answer 98

Growth pattern Predominantly solid / circumscribed; often limited peripheral infiltration Frequent extension into subarachnoid space **Biphasic appearance** **Compact** fibrillar portions: elongated nuclei, bipolar piloid processes, Rosenthal fibers **Loose** microcystic portions: round to oval nuclei, cobweb-like processes, eosinophilic granular bodies

Question 99

What is Rosenthal fiber? What pathology?

Answer 99

A Rosenthal fiber is a thick, elongated, worm-like or "corkscrew" eosinophilic (pink) bundle that is found on staining of brain tissue in the presence of **long-standing gliosis**, occasional tumors, and some metabolic disorders. **Pilocytic astr.**

Question 100

Pleomorphic xanthoastrocytoma general attributes

Answer 100

low grade astrocytoma age: 7-25 Majority of tumors occur supratentorially, most commonly in **temporal lobes** (seizures!) Often superficially located with involvement of the overlying leptomeninges Many patients present with long history of epileptic seizures occasionly transform to GBM

Question 101

Pleomorphic xanthoastrocytoma histology

Answer 101

bizarre pleomorphic cells xanthomatous fat cells multinucleoted cells

Question 102

Pleomorphic appereance histology

Answer 102

Question 103

Subependymal giant cell astrocytoma (SEGA)

Answer 103

Benign, slowly growing tumor typically arising in wall of lateral ventricles and composed of large ganglioid astrocytes Usually associated with **tuberous sclerosis** Near foramen Monroe --> hydrocephalus!

Question 104

Tuberous sclerosis complex

Answer 104

seizures, retardation, sebaceous adenomas TSC1 Ch9 = hamartin TSC2 Ch16= tuberin subependymal calcification

Question 105

Diffuse gliomas

Answer 105

**fibrillary** (most frequent) **protoplasmic** **gemistocytic** (worst prognosis mixed Grade: anaplasia, cellualrity, nucl. plomorffism, endothel. prolif., necrosis, pseudopalisading * Mutations in **IDH1/2, ATRX, TERT, and TP53 and co-deletion of 1p/19q** correlate better with tumor biological and clinical behavior than do stratifications based only on histological features

Question 106

Gliomas 2021 WHO changes

Answer 106

Standardization with other fifth edition WHO classification systems (Neuro Oncol 2021;23:1231) Switch from Roman to Arabic numeral system The term "type" replaces "entity" and "subtype" replaces "variant" Shift toward within tumor type grading - Removal of modifier terms, such as anaplastic - IDH mutant astrocytic gliomas were 3 separate entities under the 2016 WHO (diffuse astrocytoma, anaplastic astrocytoma and glioblastoma) but now fall under the single tumor type **astrocytoma, IDH mutant, with CNS WHO grade ranging from 2 to 4** - Oligodendroglioma, IDH mutant and 1p / 19q codeleted, is assigned a CNS WHO grade of 2 or 3 - Pleomorphic xanthroastrocytoma is assigned a CNS WHO grade of 2 or 3 - Terms that are no longer recommended include diffuse astrocytoma, anaplastic astrocytoma, glioblastoma IDH mutant, anaplastic oligodendroglioma and anaplastic pleomorphic xanthoastrocytoma

Question 107

Gliomas WHO 2021 new subgroups

Answer 107

New tumor type groupings - Adult type diffuse gliomas - Pediatric type diffuse low grade gliomas - Pediatric type diffuse high grade gliomas - Circumscribed astrocytic gliomas New glioma types - Diffuse astrocytoma, MYB or MYBL1 altered - Polymorphous low grade neuroepithelial tumor of the young - Diffuse low grade glioma, MAPK pathway altered - Diffuse hemispheric glioma, H3 G34 mutant - Diffuse pediatric type high grade glioma, H3 wildtype and IDH wildtype - Infant type hemispheric glioma - High grade astrocytoma with piloid features

Question 108

Adult type diffuse gliomas astrocytoma, IDH mutant

Answer 108

**IDH1 / IDH2 mutated,**diffusely **infiltrating** glioma, most often with concurrent **TP53 or ATRX** mutations and without 1p / 19q codeletion Can be graded CNS WHO grade 2, 3 or 4 IDH1 codon 132 or IDH2 codon 172 mutated, diffusely infiltrating glioma without 1p / 19q codeletion and usually with TP53 or ATRX mutations In the absence of 1p / 19q codeletion, a component that morphologically resembles oligodendroglioma is compatible with this diagnosis Can be designated CNS WHO grade 2, 3 or 4 depending on presence of *mitotic activity, nuclear atypia, pleomorphism, necrosis, microvascular proliferation or CDKN2A / CDKN2B homozygous deletion* Significant proliferative activity is consistent with a CNS _WHO grade 3_ diagnosis Presence of either necrosis, microvascular proliferation or CDKN2A / CDKN2B homozygous deletion is consistent with a CNS _WHO grade 4_ diagnosis

Question 109

Infiltrating gliomas histology

Answer 109

**Typical histologic features of infiltrating gliomas. In diffuse astrocytomas (a), cellularity is increased due to infiltrating neoplastic astrocytes with irregular, hyperchromatic nuclei and scant associated cytoplasm.** Immunohistochemistry for IDH1 R132H mutant protein (A, inset) can be helpful when infiltrating cells are sparse or rare. b Anaplastic astrocytoma is distinguished by mitotic activity (black arrow). Note the infiltrating tumor cells around a non-neoplastic neuron (white arrowhead). c **Palisading necrosis** (left) and endothelial proliferation (upper right) are histologic features of glioblastoma, though neither feature is absolutely specific.

Question 110

Gemiostocytic astrocytoma

Answer 110

worst prognosis Gemistocytes are polygonal cells with peripherally displaced nuclei and glassy cytoplasm, as well as coarse processes. Despite the tumor's aggressive behavior, mitoses are usually hard to find

Question 111

Genetic alteration in gliomas

Answer 111

Question 112

Oligodendroglioma, (IDH mutant, 1p / 19q codeleted)

Answer 112

CNS WHO 2021 definition: diffusely infiltrating glioma with IDH1 or IDH2 mutation and codeletion of chromosome arms 1p and 19q (CNS WHO grade 2 or 3) Essential features Diffusely infiltrating glial neoplasm with **IDH1 or IDH2 mutation and 1p / 19q** whole arm codeletion (both features are required for diagnosis) Morphology resembles nonneoplastic oligodendrocytes with round monotonous nuclei and perinuclear halos **Chicken wire vasculature,** microcalcifications and microcysts are characteristic Median overall survival: 11.6 years; 10 year overall survival rate: 51 - 63% *Unfavorable features*: Contrast enhancement on MRI CNS WHO grade 3 histology **CDKN2A / CDKN2B homozygous deletion** Local recurrence and malignant transformation are common

Question 113

Classic oligodendroglioma features

Answer 113

perinuclear halo = **fried egg** (= citoplasma retractio --> artefitial! not in frozen sample) present with seizure higher frequency of hemorrhage have calcification Greenberg: ● slow growing tumor that frequently presents with seizures ● occur primarily in adults, predilection for the frontal lobes (F>T) ● by definition: a diffusely infiltrating glioma with **codeletion of BOTH chromosome arms 1p AND 19q, AND mutation of IDH1 OR IDH2** ● histology: classic features of “fried egg” cytoplasm (on permanent pathology) & “chicken wire” vasculature are unreliable. Calcifications are common ● recommended treatment: as for WHO grade II astrocytic tumors

Question 114

Gliosarcoma

Answer 114

Rare, classic variant of glioblastoma (GBM), WHO grade 4 **Biphasic glial and mesenchymal differentiation** 2% of GBM, 40-60y, temporal lobe, dural invasion GBM component GFAP stains intra-extracranial metastasis **Sarcoma: from vascular structures** Median overall survival with treatment (both primary and secondary gliosarcoma): 17.5 months (J Neurooncol 2015;125:401) Median overall survival with treatment: 24.7 months

Question 115

Optic glioma

Answer 115

Relatively rare Slow growing tumor within orbital segment of optic nerve Usually ages 0 - 9 years with symptoms of minimal exophthalmos, optic nerve atrophy or papilledema Associated with neurofibromatosis type 1

Question 116

Glioblastoma subtypes

Answer 116

- giant cell GBM - gliosarcoma - epitheloid GBM

Question 117

Glioblastoma, IDH wild type

Answer 117

An aggressive, infiltrating, astrocytic glioma that lacks mutations in IDH1, IDH2 and histone H3 genes and is: Histologically defined by brisk mitotic activity and microvascular proliferation or necrosis Or molecularly defined by the presence of TERT promoter mutation, EGFR gene amplification or copy number changes in the form of combined gain of chromosome 7 and loss of chromosome 10 **TERT, EGFR, +7/-10** no IDH!

Question 118

Necrosis in GBM

Answer 118

Question 119

GBM favorable factors

Answer 119

- KPS >80 - younger age - IDH1 mut - MGMT promoter methylation (unmethlyated medisan OS 12.2 m; methy.: median OS 18.2m) **worst: IDH wild, MGMT unmeth., biopsy, 50y older**

Question 120

RANO criteria

Answer 120

RANO criteria is a set of guidelines used to assess treatment response in patients with glioblastoma, a type of brain cancer. The criteria include four categories: complete response, partial response, stable disease, and progressive disease. These categories are based on changes in tumor size, enhancement, and clinical status.

Question 121

MR spectroscopy

Answer 121

ChoCrNALaLi **CHOCNALALI** lactate: endproduct of anaerob glycolysis (hypoxia) N-acetyl-aspartate: neuronal marker, tallest peak (csökkent in ALL abnormalities) cholin: marker of membrane synthesis (stroke is low) GLIOMAS: higher lactate, lipid, cholin, lower NAA (higher the choloin, higher the grade!) ABCESS: low NAA, Cr, CHo; atypical paeks (from baci --> succinate, acetate...), lavetate can be elevated

Question 122

Glioma MRS

Answer 122

csökk NAA; növ: lactate, lipid, cholin

Question 123

Ependymomas (of post. fossa) key concepts

Answer 123

● usually benign tumors, often fibrillary with epithelial appearance. **Perivascular pseudorosettes or ependymal rosettes** may be seen ● most often occur in the **floor** of the 4th ventricle, presenting with hydrocephalus (increased ICP) and cranial nerve VI & VII palsies ● evaluation: includes imaging the entire neuraxis (MRI with and without enhancement: cervical, thoracic, lumbar & brain) because of potential for seeding through CSF ● worse prognosis the younger the patient (especially age < 24 months) ● treatment: the best outcomes are associated with gross total removal (no enhancing tumor on post-op MRI) followed by XRT. XRT may be withheld for age < 3 years due to side effects ● do LP ≈ 2 weeks post-op to send ≈ 10 cc of CSF for cytology for prognostication

Question 124

Ependymomas general

Answer 124

Essential features Well circumscribed tumor of ependymal differentiated cells that occurs in the supratentorium, posterior fossa and spinal cord **Bimodal age distribution** of children and adults, occurring equally between genders Is classified and prognosticated by location, histology and molecular and methylation studies Supratentorial ependymomas can have **ZFTA fusions or YAP1 fusions**; posterior fossa ependymomas are split into posterior fossa group A (PFA) and posterior fossa group B (PFB) by methylation profile; spinal ependymomas can have MYCN amplification

Question 125

Specific ependymoma types

Answer 125

- supratentorial - supratentorial ZFTA-fusion + (ZFTA fused w/ RELA) - supratentorial YAP1 fusion + - posterior fossa - posterior fossa Group A - posterior fossa Group B - spinal ependymoma - spinal ependymoma MYCN amplified - myxopapillary ependymoma - subependymoma

Question 126

Ependymoma types 2021 WHO

Answer 126

Overview of key characteristics and diagnostic criteria of the distinct ependymoma tumor types as proposed by the 2021 WHO Classification of CNS tumors. Range of age (in years) at onset of disease is indicated in black, the median age of onset is highlighted with a red triangle. PFS and OS are rated on a scale of green (very low progression rate and good OS), orange (intermediate PFS and OS) to red (high progression rate and dismal survival prognosis). For SE, we highlighted that tumors with supratentorial or spinal location have a low progression rate. In contrast, SE of the PF have a higher tendency to progress. Typical molecular features described to date are indicated for each tumor type. Obligatory criteria for the diagnosis of all ependymoma types are morphological and immunohistological features of ependymoma. Additional obligatory criteria are listed for each tumor type. Also, the 2021 WHO Classification provides desirable criteria for the diagnosis of each tumor type that can support the diagnosis. CNP, copy number profile; MPE, myxopapillary ependymoma; NEC, not elsewhere classified; NOS, not otherwise specified; OS, overall survival; PF, posterior fossa ependymoma; PF-A, group A posterior fossa ependymoma; PF-B, group B posterior fossa ependymoma; PFS, progression free survival; SE, subependymoma; SP-EPN, spinal ependymoma; SP-MYCN, MYCN-amplified spinal ependymoma; ST, supratentorial ependymoma; ST-YAP1, YAP1-fusion positive ependymoma; ST-ZFTA, ZFTA-fusion positive ependymoma

Question 127

Ependymoma mutations and locations

Answer 127

Question 128

Ependymal rosettes

Answer 128

true rosettes perivascular rosettes

Question 129

Choroid plexus papilloma

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Rare intracranial tumor arising in the ventricle, mainly occurring in children 3 histological grades (WHO grade 1, 2, 3): **choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), choroid plexus carcinoma (CPC)** Histological classification is based on architecture (preservation of papillary pattern), cellular density, cytology (nuclear pleomorphism), proliferation (mitoses) and necrosis / brain invasion Diagnostically, transthyretin (TTR), KIR7.1, cytokeratin and Ki67 immunohistochemistry are most helpful Based on methylation profiling, these tumors are now categorized in to 3 subtypes In line with other CNS tumors, integrated phenotype genotype diagnosis is preferred, which will guide appropriate management

Question 130

Choroid plexus papilloma histology

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Choroid plexus papilloma are benign tumors with preserved papillary or finger-like architecture, with fibrovascular cores, lined by single layer of cuboidal to columnar epithelium, almost resembling nonneoplastic choroid plexus but with mild cellular atypia and without significant mitotic activity.

Question 131

Choroid plexus carcinoma

Answer 131

mostly children lat ventricles 40% @ LiFraumeni sy --> TP53 mutation