Tumors

1. Pediatric Intramedullary Spinal Cord tumors

1.1. Astrocytoma, cervicothoarcic, enhance variably

1.2. Ependymoma, cervical location, enhance avidly, cap sign representing hemosidering (low signal) and syringomyelia

1.3. Turcots syndrome, tuberouswclerosis and NF2

1.4. Conus involvement causes sphincter dysfunction w/o bladder or bowel dysfunction

1.5. Treatment

1.5.1. Surgery

1.5.1.1. Radiation

1.5.1.1.1. Low grade astrocytoma and ependymoa w GTR can be followed w serial imaging

1.5.1.1.2. High grade tumor, recurrent and subtotal resection

1.5.1.1.3. EXBRT

1.5.1.2. Spine deformity: <13 yr, preop deformity, multiple resections, adjuvant RT and resection at thoracolumbar junction

1.5.1.2.1. consider fusion at the time resection

1.5.1.2.2. consider in situ fusion for multilevel sgx >3 levels

1.5.1.3. Osteoplastic laminotomy, US, MEPS, SEEPs, EMG and D-wave. Dorsal colum stimulation.

1.5.2. Chx as bridging Tx if pat <3yr

1.6. Ependymoma>astrocutyma (pilocystic MCC and better prognosis; malignant astrocytomas; GBM w hydrocephalus and dissemination. Median survival rates 6 m.

2. Nerve sheath tumors

2.1. Schwannomas

2.1.1. Essentic growth encapsulated within epinerium capsule

2.1.2. CNVIII and entry zone spinal senory

2.1.3. GTR and SRS

2.2. Neuromas

2.2.1. Not true neoplasm - inflammatory nidus consisting of Schwann cells, fibroblast and axons.

2.2.2. Rubbery and painful

2.3. Neurofibromas

2.3.1. Unencaspulated fusiform benign neoplasm that require nerve transection for complete removal

2.3.2. Not painful

2.4. Maligant peripheral nerve sheath tumors

2.4.1. Painful

2.4.2. NF1 50%

2.4.3. Resection and radiation

3. Germ cell tumors

3.1. Location pineal gland, neurohypophysis and basal ganglia

3.2. Germinoma

3.2.1. Two-cell pattern and cobblestone arrangement of large tumor cells with interstitial inflammatory cells

3.2.2. Upward gaze can be affected by compression of the tectum

3.2.3. CT detecting calcification, which may suggest a teratoma component

3.2.4. Radiation sensitive

3.2.5. Bifocal or synchronous tumors at neurohypophysis and pineal gland are pathognomonic

3.2.6. hCG positive

3.3. Nongerminomatous Germ Cell Tumors

3.3.1. Embryonal carcinoma

3.3.1.1. Pluripotent cells with inability to become germ cells.

3.3.1.2. Very maligant

3.3.1.3. positivity for cytokeratin, CD30, LIN28A, Oct4, and placental alkaline phosphatase (PLAP)

3.3.2. Yolk sac tumors

3.3.2.1. Endoermal sinus tumor

3.3.2.2. Schiller–Duval bodies glomeruli-like

3.3.2.3. AFP positive

3.3.3. Choriocarcinoma

3.3.3.1. Syncytiotrophoblasts and cytotrophoblasts

3.3.3.2. Intratumoral hemorrhage

3.3.3.3. Positive to β-hCG, cytokeratin, and EMA.

3.3.3.4. Hemorrhage: choricocarcinoma

3.3.4. Teratoma

3.3.4.1. Tissue derived from two or three germ layers (ectoderm, mesoderm, and endoderm), i.e. skin,bone etc.

3.3.4.2. Maligant degeneration into squamous cell carcinomas, adenocarcinomas, and rhabdomyosarcomas

3.3.5. Mixed germ cell tumors

4. Intraventricular tumors

4.1. Primary

4.1.1. Linning of ventricles

4.1.1.1. Ependymomas

4.1.1.1.1. NF2

4.1.1.1.2. Glial tumors w ependymal diff

4.1.1.1.3. 4th ventricle

4.1.1.1.4. Grade II

4.1.1.2. Subependymomas

4.1.1.2.1. Grade I

4.1.1.2.2. Glial tumors from subependymal layer attached to ventricular wall by a narrow pedicle

4.1.1.2.3. 4th ventricle >lateral ventricle

4.1.1.2.4. Incidental and can be managed conservatively

4.1.1.3. Colloid cysts

4.1.1.3.1. Bening 3rd ventricle epithelium lined cyst

4.1.1.3.2. Usually Asx ranging from few mm to 4cm, w resulting hydrocephalus and even sudden death

4.1.1.3.3. Filled w mucin, hemosiderin and cholesterol

4.1.1.4. Neurocytomas

4.1.1.4.1. Grade II

4.1.1.4.2. Rarely associated w sudden death

4.1.1.4.3. Foramen monro/3rd ventricle

4.1.1.4.4. histiologically appear very similar to oligodendrogliomas, salt-and-pepper apperance

4.1.1.4.5. Sgx currative

4.1.1.5. SEGAS

4.1.1.5.1. Not of astocystic origin

4.1.1.5.2. Almost exclusively associated w tuberous sclerosis

4.1.1.5.3. Asx unless large enough to cause hydrocephalus

4.1.1.5.4. MRI

4.1.1.5.5. mTOR inhibitors

4.1.2. Structures

4.1.2.1. Chorid plexus

4.1.2.1.1. Papillomas

4.1.2.1.2. Carcinomas

4.1.2.1.3. VHL

4.1.2.1.4. Hydrocephalus in 80% pat due to CSF overproduction

4.1.2.1.5. Commonly located supratentorially in children and infratentorially in adults

4.1.2.1.6. Angiography shows prominent blush w enlarged choroidal arteries

4.1.2.2. Meningomas

4.1.2.2.1. MC IV tumor, F>M, 4-6th decade, L>R side

4.1.2.2.2. Meningothelial inclusion bodies in the tela choroidea or the choroid plexus

4.2. Secondary

4.2.1. Craniopharyngiomas

4.2.2. Adenomas

4.2.3. Gliomas

4.3. Approaches

4.3.1. Transcallosal

4.3.1.1. works even w small ventricles

4.3.1.2. Short trajectory 3rd ventricle

4.3.1.2.1. no cortical transgressions

4.3.1.3. Con: weakness, akinetic mutism (cingulate gyrus) and memory deficist (fornices)

4.3.2. Endoscopic

4.3.2.1. dilation of ventricles is nedded

4.3.2.2. poor control in-case of bleeding

4.3.2.3. Pro: less invasive, direct vision, short postop time and less postop seizure

4.3.3. Transcortical-transventricular

4.3.3.1. right middle frontal gyrus

4.3.3.1.1. high risk for seizure

4.3.3.1.2. need for large ventricles

4.3.4. Subfrontal

4.3.4.1. Anterior-inferior 3rd ventricle

4.3.4.2. Subchiasmal, lamina terminalis

4.3.5. Stereotactic

4.3.5.1. enter just anterior to R coronal suture

4.3.5.2. endoscopic guidance

4.3.5.3. Good for cysts >1 cm viscous

5. Pineal region

5.1. Astrocytes, fibrovascular stroma and calcifications increasing w age

5.2. Pineal apoplexy

5.2.1. Diplopia, ocular motility, BS compression and endocrine

5.2.2. Parinaud syndrome

5.2.2.1. Upward gaze paralysis, lid retraction, light-near dissociation, unreactive pupils, convergence nystagmus, retraction nystagmus

5.3. Leptomeningeal disease

5.3.1. Germinomas, pineoblastomas, choricocarcinoma, pineal parenchymal tumor of intermediate differentiation

5.4. Serum markers

5.4.1. PIAP & Beta Hcg

5.4.1.1. Germinoma

5.4.2. AFP

5.4.2.1. Yolk sac

5.4.3. Beta Hcg

5.4.3.1. Mixed germ cell

5.5. Surgical aproaches

5.5.1. Dorsal midbrain and Vein of galen corridor must expand

5.5.1.1. Flat tentorium

5.5.1.1.1. Supracerebellar

5.5.1.2. step tentorium

5.5.1.2.1. Occipital transtentorial approach

5.6. Germinoma

5.6.1. Treated w radiation alone

5.7. Nongerminomatous Germ Cell Tumor (maligant NGGCT). Tx w platinum and spinal radiation

5.7.1. Image progression w/o markers suggest Growing teratoma syndrome (teratoma remnant after treatment of maligant gem cell component

5.7.2. Embryonal carcinoma, Teratoma, yolk sac, choricocarcinoma, mixed germ cell

5.8. Teratoma

5.8.1. Multicystic, may be part of NGGCT

5.8.2. Very resistant to chz or Rt

5.8.2.1. Sgx

5.9. Pineoblastoma

5.9.1. highly maligant

5.9.2. Chx and craniospinal RT

5.9.2.1. <3 yr no radiation

5.9.3. Trilateral retinoblastoma

5.10. Pineocytoma

5.10.1. low grade maligant

5.10.2. responds very well to surgical resection

5.11. Pineal parenchymal Tumor of Intermediate Differentiation

5.11.1. Intermediate maligance b/w pineoblastoma & pienocytoma

5.11.2. MIB-1 suggest more maligant

5.11.3. Tripple Tx

5.12. Papillary tumor of the Pineal region

5.12.1. Maligant tumors

5.12.2. GTR

5.13. Pineal cysts

5.13.1. Should be treated in children if Sx or growing

5.13.1.1. Grow during childhood

5.13.2. in adulthood the cyst may remain stable

5.13.2.1. can be followed if no Sx

5.13.3. Cyst >1-2 cm have greater tendency to be symptomatic

5.13.4. HA, hydrocephalus

5.13.5. Sudden headache may be due cyst apoplexy

5.13.5.1. Sgx

5.14. Rosette-forming Glioneuronal tumor of the pineal gland

5.14.1. Pineal gland or 4th ventricle

5.14.1.1. Responds very well to sgx, even subtotal

6. Acoustic Neuroma

6.1. Super division of VIII

6.1.1. sporadic

6.1.1.1. unilateral

6.1.1.2. 3rd-4th decade

6.1.2. NF2 5%

6.1.2.1. bilateral

6.1.2.2. younger

6.2. 8% of all intracranial tumors

6.3. Diagnosis

6.3.1. Asymmetric sensorineurnal hearing loss

6.3.1.1. predilection for higher freqency

6.3.1.2. Auditory Brainstem Response

6.3.1.2.1. delay in nerve conduction

6.3.1.2.2. upper limit of normal 0.2 ms

6.4. MRI GI enhanced

6.4.1. can detect 3-4 mm small lesions

6.4.2. Isointense T1 and T2

6.4.2.1. Homogenous enhancement on GI

6.5. Indications

6.5.1. Normal growth 0.6-3.4 mm/yr

6.5.2. Despite hearing loss w rapid tumor growth there is still excellent CNVII preservation rate

6.5.3. hearing preservation

6.5.3.1. >2.5 mm/yr

6.5.3.2. <2.5 mm/yr

6.5.3.3. Wait-and-see

6.5.3.3.1. 2.77-5.39 dB/yr hearing loss

6.6. Sgx

6.6.1. Middle fossa

6.6.1.1. better facial and hearing preservation as long as tumor <1.5 cm

6.6.2. Rectosigmoid

6.6.2.1. higher CNVII and hearing preservation for tumors >1.5 cm (or even >3 cm)

6.6.2.1.1. More postoperative HA and CSF leaks

6.6.3. Translabyrinthine

6.6.3.1. For pat with compromised hearing

6.6.3.1.1. Less HA and CSF leaks

6.6.4. Significant greater risk for V and VII funtional damage when comparing Sgx vs SRS

6.6.4.1. No diffrence in in tumor control vs SRS

6.7. SRS/LINAC

6.7.1. 12-14 Gy

6.7.2. High rate of tumor control & facial nerv function

6.7.2.1. lesions <3 cm

6.7.2.2. >90%-65%-98%

6.7.3. Hearing preservation 57-75%

6.8. Fractionated radiotherapy

6.8.1. Fractionated conventional RT

6.8.2. Fractionated stereotactic RT

6.8.2.1. More conformal radiation

6.8.2.2. 1.8-5 Gy

6.8.2.2.1. in total 20-57.6 Gy

6.8.2.3. Similar facial nerve function preservation and tumor control but mixed hearing preservation

6.8.2.3.1. lesions >3 cm

7. Posterior fossa tumors

7.1. most common

7.1.1. total metastasis

7.1.1.1. total 15% of all mets are in the cerebellum

7.1.1.2. 5% in the BS

7.1.1.3. Lung, breast, skin, kidney and colon

7.1.2. primary hemangioblastoma

7.1.2.1. 10% of primary posterior fossa

7.1.2.2. VHL chromosome 3

7.1.2.2.1. Retianl anc CNS hemangioblastoma

7.1.2.3. angio

7.1.2.3.1. vascular blush

7.1.2.3.2. fast filling and early washout

7.1.2.4. MRI

7.1.2.4.1. peritumoral cyst formation

7.1.2.5. Sgx with complete removal of the nodule

7.1.2.5.1. cyst wall removal is not needed

7.1.2.5.2. sgx is only needed when Sx

7.2. Cerebellar Pilocystic Astrocytoma

7.2.1. Survival is good

7.2.2. Cyst w contrast enhanced mural nodule

7.2.3. will lack the blush seen in the hemangioblastoma on angio

7.2.4. GTR

7.2.4.1. Cyst wall does not have to resected but Bx should ne taken

7.2.4.2. Radiation fo subtotal resection

7.3. 4th ventricle choroid plexus tumors

7.3.1. Rare in genral, even more so in adults

7.3.2. benign papilloma grade I, atypical grade II and carcinoma grade III

7.3.2.1. Heterogenous enhancement is suggestive of grade III

7.3.2.2. Sgx for lower grades and chz/RT for larger ones

7.3.2.3. Sgx for lower grades and chz/RT for larger ones

7.4. Brainstem glioma

7.4.1. adult gliomas are either low grade or high grade

7.4.1.1. low grade more common

7.4.1.2. Lesions are difffuse and surgical resection is hard

7.4.1.2.1. Radiation is primary treatment

7.4.1.3. High grade lesions enhance w contrast and exhibit areas of necrois and peritumoral edema

7.5. Medulloblastoma

7.5.1. Maligant

7.5.1.1. common in pediatric and rare in adults

7.5.2. midline verminan region

7.5.2.1. obstructive hydrocephalus

7.5.2.1.1. avoid shunting if possible as metastasis may occur

7.5.2.1.2. avoid shunting if possible as metastasis may occur

8. Clival tumors

8.1. Chordomas

8.1.1. slow-growing from the remnants of the primitive notochord

8.1.1.1. extradural clival tumors

8.1.1.1.1. spheno-occipital synchondrosis

8.1.1.2. skull base/spine>sacrum

8.1.2. histology

8.1.2.1. clear vaculoes and large septas

8.1.2.1.1. stains w brachyury, SOX-9 and podoplaning (to ddx from chondrosarcomas)

8.1.3. indolent tumors

8.1.3.1. diplopia and HA

8.1.3.1.1. cranial neuropathies and long tract signs

8.1.3.2. midline tumors w lytic bone destruction

8.2. Chondrosarcomas

8.2.1. orginate from cartilage producing mesenchymal cells

8.2.1.1. proximal long bones, pelvis, ribs and spine

8.2.1.2. clivus

8.2.1.2.1. majorityu are spontanous

8.2.1.2.2. may occur w Pagets, Olliers, Maffucci syndromes and Osteochondrosarcoma

8.2.1.2.3. Paramedially located unlike chondromas

8.2.1.3. diploia and HA

8.2.1.3.1. cranial neuropathies and long tract signs more common in chordomas

8.3. DDx: meningioma, paraganglioma, rhabdomyosarcoma, pituitary adenoma

8.4. Maxiumum surgical resection and high dose RT

9. Calvarial tumors

9.1. Benign

9.1.1. Epidermoid cyst

9.1.1.1. stratified sq cells

9.1.1.2. cyst filled with keratin

9.1.1.2.1. Dermoid cyst

9.1.1.3. Calvarial lesions in children at around ant fontanlele, coronal and lambdoid suture

9.1.1.4. Painless and slow growing

9.1.1.5. Surgical resection w cyst wall and avoidance of spillage that can cause severe chemical meningitis

9.1.2. Fibrous dysplasia

9.1.2.1. bone is replaced by fibrous tissue

9.1.2.2. usually begins w rapid bone growth in childhood and ceases in adulthood or puberty

9.1.2.3. sphenoid, frontal and maxillary bone

9.1.2.3.1. sclerotic, cystic or pagetoid

9.1.2.4. Symptomatic painful and deformity and optic nerve compromise

9.1.2.4.1. prophylatic optic decompression not indicated

9.1.3. Eosinophilic granuloma

9.1.3.1. Langerhans histiocytosis

9.1.3.1.1. epidermal dendritic cells

9.1.3.1.2. affect any organ

9.1.3.1.3. Hand-Schüller-Christian: DM, exophthalmos and lytic bone lesions usually involving the skull

9.1.3.1.4. Letterer-Siwe: Hepatomegaly, scaly skin lesions, lymphadenopathy and lytic bone lesions

9.1.3.2. M>F, frontal & parietal and painful lesions

9.1.3.3. Punched out lesions, destroy outer table>inner table

9.1.3.4. Sgx for single lesion and Chx/Rt for multiple lesion

9.1.4. Osteoma

9.1.4.1. Benign bone tumors

9.1.4.1.1. mature cortical bone

9.1.4.1.2. most common benign primary neoplasm

9.1.4.1.3. Multiple osteomas

9.1.4.1.4. Sinusitis due to sinus drainage

9.1.4.1.5. Surgery is indicated for symptomatic lesions

9.2. Maligant

9.2.1. Sarcoma

9.2.1.1. maligant tumors of mesenchymal tumors

9.2.1.1.1. Irregular, poorly marginated osteolytic lesions w/o adjacent sclerosis

9.2.1.1.2. Resection w wide margins and resection of infiltrated dura. Radiation/chx

9.2.2. Metastasis

9.2.2.1. Most common maligant tumor of the skull (adults and children)

9.2.2.1.1. Neuroblastoma

9.2.2.2. Growing skull lesion

9.2.2.2.1. neurovascular compression

9.3. Most common maligant tumor metastasis, osteoma most common primary benign and osteogenic sarcoma the most common maligant primary tumor

10. Paraganglioma

10.1. Imaging

10.2. Jugular formanen extension

10.2.1. Glomus jugulare (paraganglioma), schwannoma and meningioma

10.2.2. tumors that may invade the jugular foramen

10.2.2.1. chordoma, chondrosarcoma, endolymphatic sac tumor and metastases

10.3. other paragangliomas and pheochromocytoma

10.3.1. check urine catecholamine and urine vanillylmandelic acid levels

10.3.1.1. conversion of noepi to epi converted by PNMT present in the adrenal medulla

10.3.1.2. paragangliomas produce noepi

10.3.2. alpha and beta-blockade

10.4. very vascular lesions

10.4.1. preop embolization 3-5 days

10.4.2. generally the tumor pushes the lower cranial nerves (CN VII, IX, X, XI and CXII)

10.5. Treatment

10.5.1. RT

10.5.1.1. tumor control

10.5.1.1.1. no mortality and recurrence rate 2.1%

10.5.2. Sgx

10.5.2.1. 1.3% mortality and 3.1% recurrence rate

11. Pediatric

11.1. Gliomas

11.1.1. Low-grade

11.1.1.1. Pilocystic astocytoma

11.1.1.2. Pleomorphic xanthoastrocytoma

11.1.1.3. Ganglioma

11.1.1.4. DNET

11.1.1.4.1. Temporal and frontal lobes

11.1.1.5. WHO II

11.1.1.5.1. Astrocytoma

11.1.1.5.2. Oligodendroglioma

11.1.2. High grade

11.1.2.1. Anaplastic astrocytoma

11.1.2.2. Glioblastoma

11.1.3. Brainstem gliomas

11.1.3.1. DIPG

11.1.3.1.1. usually not resectable

11.1.3.1.2. usually not resectable

11.1.3.2. Exophytic medullary glioma

11.1.3.3. Midbrain tectal glioma

11.1.3.3.1. Pencil glioma

11.1.3.4. Clincal triad of BS gliomas: cranial nerve deficits (VII, IX or visual deficits), hemibody sens/motor and ataxia

11.2. ~70% of pediatric tumors are gliomas

11.2.1. <1 yr supratentorial, 1-5 yr infratentorial, 5-20 yr roughly equal

11.2.2. Survival decreases w increasing age except for children <1 yr old who have the lowest survival

11.2.2.1. OS/PFS are associated w extent of surgical resection and histo grade

11.2.2.2. Tumor location determines management

11.3. 0-5 yr MCC embryonal, 2nd Pilocytic astrocytoma; 5-14 yr MCC PA, 2nd Malignant glioma; 15-19 yr MCC Pituitary, 2nd PA; Overall 0-19 yr MCC PA

11.3.1. PA w 7q32 duplication that results in BRAF & KIAA1549 gene fusion has a better prognosis; more common in infratentorial than supreatentorial

11.3.2. Glioblastoma in children usually w/o EGFR/PTEN del, usally negative for IDH and MGMT methylation significance is uncertains

11.3.2.1. usually associated w tk/RAS/P13kinase; P53 (worse prognosis); retinoblastoma signaling

11.4. Primitive neuroectodermal tumors (PNET)

11.4.1. sPNET

11.4.1.1. rare, aggreisve and very large lobar/thalamic tumors

11.4.1.2. usually <5 yrs

11.4.1.3. Spread quickly

11.4.1.3.1. 30% spinal dissemination at the time of presentation

11.4.2. inferior PNET= medulloblastoma

11.4.2.1. 30% of all brain tumors in children; 50 % if all posterior fossa tumors in children

11.4.2.2. 4 subgroups

11.4.2.2.1. group 1: WNT subgroup

11.4.2.2.2. group 2: Sonic hedge hog

11.4.2.2.3. group 3: MYC amplication

11.4.2.2.4. group 4: short arm of chr 17, mcc and worse prognosis

11.4.2.3. Increased TrKC and beta-catenin: more fav prognosis

11.4.2.4. midline/4th ventricle

11.4.2.5. Truncal ataxia from cerebellar vermis

11.4.2.6. Gorlin syndrome (AD, chr 9, SHH, jaw cyst, calcified falxs; Medulloblastoma and multiple basal cell Ca). Turcot syndrome (AD, chr 15, WNT pathway, medulloblastoma, GBM, anaplastic astrocytes, ependymomas, colon ca and polyps).

11.4.3. Hyperdense, contrast enhancing and 50% cysts and calcifications.

11.4.4. GTR. radiation of tumor bed, neuroaxis and chemo

11.4.5. Leptomeningeal dissemination causes unremitting spinal pain

11.4.6. poorer prognosis for children <3 yrs bc inability to treat with RT

11.5. Non-PNETS, Nongliomas

11.5.1. Overall Leukemias>PA>glioma>PNET>Atypical teratoid rhabdoid tumor

11.5.2. Germ cell tumors (GCT)

11.5.2.1. missmigration of primordial germ cells during embryonic development

11.5.2.2. Germinoma or nongerminoma (NGGCT); 2/3 vs 1/3

11.5.2.2.1. NGGCT

11.5.2.2.2. Germinomas typically arise in the pineal or supracellar region

11.5.2.2.3. RT

11.5.2.3. Tumor markers

11.5.2.3.1. Increased AFP/bHCG: embryonal Ca

11.5.2.3.2. Increased central alkaline phosphatase: germinoma

11.5.3. Craniopharingioma

11.5.3.1. 5-15; 45-60 yrs, adamantinous (calcification) ("motor oil", polarizable cholesterol crystals) and papillary

11.5.3.2. WHO I grade

11.5.4. PCNSL

11.5.4.1. rare unless acquired or cogenital; shx for bx only, steroid Tx only

11.5.5. Hemangioblastoma

11.5.5.1. VHL; chr 3/AD; posterior fossa

11.5.5.2. renal, neuroendocrine, cystadenomas and reproductive tumors

12. Ring enhancing lesions

12.1. GBM

12.2. Lymphoma

12.3. Mets

12.4. Resolving hematoma

12.5. Tumefactive MS

12.6. Astrocytoma

13. Geminoma

13.1. Sella/pineal region

13.2. Radiosensitive

14. Radiotherapy

14.1. SRS=SRS+WBRT SRS+WBRT=WBRT+Sgx SRS+WBRT>WBRT SRS>WBRT+Sgx (Level 3)

14.2. Schwanoma

14.2.1. SRS

14.2.1.1. 14 Gy

14.2.2. FSRT

14.2.2.1. 20-57.6 Gy

14.3. Clival tumors

14.3.1. 70 Gy

14.4. Pediatric

14.4.1. >3 yr and HGG

14.4.1.1. External beam radiation

14.4.1.1.1. 54-60 Gy, delivered daily 1.8-2 Gy

14.4.1.1.2. Intramedullary

14.5. I

15. Sellar tumors

15.1. Craniopharyngioma

15.1.1. Aka Rathke's pouch or Hypophyseal duct tumors

15.1.1.1. But NOT Rathke's Cleft Cyst( !)

15.1.1.1.1. RCC are benign cystic remnants of the CRANIOPHARYNGEAL duct located at the sellar or the supracellar region

15.1.2. Bimodal presentation up to 15 yr/from 50 yr

15.1.3. 95% supracellar component

15.1.3.1. Panhypopituitarism w hypothalamic disturbances and weight gain, dysthermia and DI

15.1.3.2. Complete resection if no thalamic or optic components are present

15.1.3.3. RT

15.1.3.3.1. AE: Cavernomas, vascular malformations, meningiomas and maligant optic gliomas

15.1.3.4. Hormone panel work-up

15.1.3.4.1. 1) AM cortisol, 2) 17-hydroxycortisone, 3) GH, 4) prolactin, 5) T4, 6) FSH 7) LH 8) estradiol or testoserone 9) urinary free cortisol

15.1.3.4.2. endocrine dysfunction occurs in 90% pat

15.1.4. Adamantinomatous

15.1.4.1. Children

15.1.4.1.1. 70% mutation of Beta-catenin

15.1.4.2. Calcifications

15.1.4.3. Remnant of craniopharyngeal duct b/w Rathke's pouch and stomodeum

15.1.4.4. Mucin producing cells w goblet cells/columnar epithelium

15.1.4.4.1. Wet-keratin

15.1.4.4.2. Piloid gliosis w Rosenthal fibers

15.1.4.4.3. Granulomatous inflammation w Giant cells

15.1.4.5. 10x more common than papillary CPs

15.1.5. Papillary

15.1.5.1. Older

15.1.5.1.1. V600E and BRAF

15.1.5.2. Lack calcifications, goblet cells or cilliated epithelium

15.1.5.3. Metaplasia of adenohypophysial cells in the pars tuberalis

15.1.5.3.1. Picket fence-like pallisades

15.1.5.4. More often located around 3rd ventricle

15.1.6. Squamous cells of the pituitary stalk - tuber cinereum

15.1.6.1. MC nonneuroepithelial intracerebral tumor

15.1.7. Approaches; Sellar (transphenoidal), Supracellar (subfrontal if prefixed, pteronial for postfixed)

15.2. Pituitary tumors

15.2.1. Typical/atypical, functional/nonfunctional

15.2.1.1. 30% nonfunctional

15.2.1.2. >50% microadenomas

15.2.1.2.1. Secretory

15.2.1.3. Gonadotrophic secret LH, FSH but is clinically silent and present as macroadenomas

15.2.1.4. 3rd-6th decade of life

15.2.1.4.1. Secretory present earlier

15.2.1.4.2. nonfunctional present later due to mass effect

15.2.2. adenoma/carcinoma

15.2.2.1. Prolactinoma

15.2.2.1.1. Dopamine

15.2.2.1.2. MC functional

15.2.2.1.3. PRL levels=size

15.2.3. ACTH/GH/TSH

15.2.3.1. Dexametasone-suppression test

15.2.3.1.1. Inferior petrosal sampling

15.2.4. Pituicytomas

15.2.4.1. Rare, low-grade

15.2.4.2. Posterior hypophysis/ neurohypophysis

15.2.5. Management

15.2.5.1. Asx microadenomas that do not enlarge: observation

15.2.5.2. Asx Macroadenomas: observation w visual field and serial imagning.

15.2.5.3. Prolactinomas: Dopamine agonist (bromocriptine and cabergoline)

15.2.5.4. Somatotrophs: octreotide (suppress hromone prduction and causes tumor to shrink)

15.2.5.5. Pituitart apoplexy: Sgx and steroid replacement

15.2.6. Dgx

15.2.6.1. Imaging

15.2.6.1.1. Delayed contrast enhancement + less enhancement than normal tissue

16. Maligant Gliomas

16.1. MC primary maligancy/3rd intracranial maligancy

16.2. M>F

16.3. Familal 6%

16.3.1. BF type1&2 and Li-fraumeni

16.4. HA, seizures, personality changes and focal neurological changes

16.5. MRI

16.5.1. Irregular, poorly marginated, Gd enhancing lesions on T1 with ring enhancement

16.5.1.1. 40% of anaplastic astrocytomas do not enhance

16.5.2. No diffusion restriction

16.5.2.1. Hypointense on DWI

16.5.3. Spectroscopy

16.5.3.1. Proliferation (ratio choline/N-acetylasparate) and necrosis (lactate) suggest higher grade lesions

16.6. Anaplastic gliomas WHO III

16.6.1. Astrocytomas

16.6.2. Oligodendrogliomas

16.6.2.1. Histo: Fried-egg

16.6.3. Oligoastrocytes

16.6.4. Sgx/Bx and RT or Chz

16.6.4.1. Except for anaplastic astrocytomas WHO III gliomas are often treated w RT or Chx

16.7. GBM WHO IV

16.7.1. 80% de novo

16.7.2. Pseudopalisades

16.7.3. Keles/Laurix suggest that removal of 60% vs 89% of lesion strongly correlates with survival and tumor progress. UCSF suggested ~80%

16.7.4. Adjuvant therapy

16.7.4.1. FRT

16.7.4.1.1. 1.8 Gy x33

16.7.4.2. Chz

16.7.4.2.1. TMZ

16.7.4.2.2. Procarbazine, Lomustine and Vincristine

16.7.4.3. 2nd line therapy

16.7.4.3.1. Anti-vascular endothelial growth factor (anti-VEGF) and Bevacizumab

16.7.4.4. Molecular markers

16.7.4.4.1. metyhlated MGMT

16.7.4.4.2. 1p19q codeletion confers improved prognosis

16.7.4.4.3. IDH1 (astrocytomas) and IDH2 (oligodendrogliomas) mutation

16.7.4.4.4. Lack of amplification of EGFR/EGFRvIII

17. Glial tumors

17.1. Grade I

17.1.1. Pilocytic astrocytomas

17.1.2. Subependymal giant cell astrocytoma

17.1.3. Subependymoma

17.2. Glioneuronal tumors

17.2.1. Pleomorphic xanthoastrocytoma

17.2.1.1. Children-Adolescents

17.2.1.2. Seizures

17.2.1.3. Superficial cortex, supratentorial, temporal lobe

17.2.1.4. Leptomeningeal

17.2.1.5. Cystic lesion and mural nodule

17.2.1.6. Calcifications are rare

17.2.1.7. Grade II, typically lack mitotic activity and lack of necrosis -> PXA anaplastic features Grade III

17.2.1.8. GTR

17.2.2. Dysembryoplastic Neuroepithelial Tumor

17.2.2.1. Children-Adolescents

17.2.2.2. Medically resistant seizures

17.2.2.2.1. Peritumoral cortical dysplasia

17.2.2.2.2. Post Sgx 80% improvement

17.2.2.3. Indolent and slow growing

17.2.2.3.1. Grade I

17.2.2.4. Temporal and frontal lobes

17.2.2.4.1. Cystic/bubbly

17.2.2.5. GTR

17.2.3. Ganglioglioma

17.2.3.1. MC temporal lobe EP

17.2.3.1.1. Can occur anywhere but 85% located in the temporal lobe

17.2.3.1.2. Partially cystic w nodule

17.2.3.2. M>F

17.2.3.3. Tendency to calcify

17.3. Cystic/bubbly

17.4. Grade II

17.4.1. Low grade astrocytoma

17.4.2. Mixed oligoastrocytoma

17.4.3. Presentation MC partial complex seizures, clinically undetected frequently

17.4.3.1. levetiracetam unlike phenytoin does not induce cytochrome P450 enzymes

17.4.4. growth 4.1 mm/y

17.4.5. Bx, Sgx, Chx, Rt

17.4.5.1. Bx 6% complication rate, 2% mortality rate and 8% failed bx

17.4.5.2. Intraoperative stimulation mapping: rolandic cortex, supplementary motor area, corona radiata, internal capsule and uncinate fascuculus

17.4.5.3. Awake language mapping: dominant hemisphere frontal operculum, temporal lobe or angular gyrus

17.5. Grade III

17.5.1. Anaplastic astrocytoma

17.5.1.1. Oligodenroglioma

17.5.1.1.1. Frontal lobes

17.5.1.1.2. Fried egg and chicken wire

17.5.1.1.3. Adults

17.5.1.1.4. Calcification

17.5.1.1.5. Anaplastic oligodendroglioma III vs Oligodenroglioma II

17.5.1.1.6. 1p19q deltion

17.5.1.1.7. IDH2

17.6. Grade IV

17.6.1. Glioblastoma multiforme

17.6.2. M>F

17.6.2.1. 60+

17.6.3. HA, seizures, personality changes and focal neurological

17.6.3.1. HA: early morning, asymmetrically, ipsilateral

17.6.4. Radiology: Irregular, poorly marginated, Gs enhanced on T1 hyperintense on T2

17.6.4.1. 40% of anaplastic astrocytomas lack enhancement

17.6.4.2. GBM typically have hemorrhage and necrosi

17.6.4.2.1. May be seen in corpus callosum and make it hard to diff from Lymphomas

17.6.4.3. DDx abscess have diffusion restriction on DWI and apperar hyperintense gliomas are hypointense

17.6.4.4. Spectroscopy: lactate (necrosis), ratio of choline to N-acetylaspartate (proliferation)

17.6.5. Pseudopalisades

17.6.6. Resection extent: Keles 60% of GD T1/T2, Lacroix 89% increases survial and 98% increased median survival 8.8 m to 13 m, USCF >78%

17.6.7. FRT 1,8 x33 =59.4 Gy w a margin of 2 cm beyond FLAIR bc local recurrence up to 80%

17.6.8. 1st line adjuvant therapy

17.6.8.1. 2nd line anti-VEGF and Bevacizumab

17.7. Prognosis oligodenroglioma>mixed astrocytomas>low grade astrocytoma (worse)

17.8. Molecular markers

17.8.1. P53

17.8.1.1. 1/3 of low grade diffuse astrocytomas

17.8.2. PTEN/FGFR

17.8.2.1. Upregulation seen in high-grade gliomas

17.8.3. 1p/19q deletion

17.8.3.1. Oligodenroglioma

17.8.3.2. PCV Chx and TMZ Chx

17.8.4. Methylation of MGMT

17.8.4.1. High grade

17.8.4.1.1. TMZ Chx

17.8.5. IDH1/2

17.8.5.1. Low grade gliomas

17.8.5.1.1. GBMs that have arisen from pre-existing low-grade tumors

17.8.5.1.2. IDH1 oligodendroglioma

17.8.5.1.3. IDH2 astrocytoma

17.8.6. Li fraumeni & NF1/2

17.8.7. Lack of EGFR mutation

17.8.7.1. Decreased proliferation capacity

17.9. UCSF prgnostic score

17.9.1. location of tumor in eloquent cortex

17.9.2. KPS <80

17.9.3. >50y

17.9.4. >4cm

17.9.5. >4 pt 56% 5-year survival

18. Mesenchymal tumors

18.1. Meningomas

18.1.1. arachnoid cap cells

18.1.1.1. F>M 2:1, cranial>spine 10:1 or 10% spinal, older age

18.1.1.2. arachnoid granulations along venous sinuses

18.1.2. Ionization radiation, NF2 chr 22

18.1.2.1. Progesterone receptors 50%

18.1.2.2. Multiple meningomas occur in 1-9% of sporadic cases and as a feature of NF2

18.1.2.3. 2-fold increased risk in F w breast Ca/BRCA1

18.1.2.4. SNPs, BRIP1/ATM

18.1.3. Grade I-III

18.1.3.1. Benign I

18.1.3.2. Atypical II

18.1.3.2.1. Mitoses >4/10hpf, small cell formation, prominent nuclei, sheetlike growth and areas of necrosis

18.1.3.3. Anaplastic III

18.1.3.3.1. Mitoses >20/10hpf, necrosis

18.1.4. Stain w positive EMA/Vimetin, negative s-100

18.1.4.1. DDx w Hemangioperiocytomas (metastasize 25-60%)

18.1.5. Grow 2-3 mm/y

18.1.6. Management

18.1.6.1. Observation if w/o parenchymal compromise and no neurovascular issues

18.1.6.1.1. Lack of T2 hyperintensity, peritumoral edema, calcification, irregular tumor borders and volumetric growth <1ml/yr

18.1.6.1.2. Symptomatic vs asymptomatic 4.3 vs 2.4 cm

18.1.6.2. Sgx

18.1.6.2.1. Simpsons grade

18.1.6.3. Chemo

18.1.6.3.1. Hormonal therapy w/o improvement in progression free survival (Mifepristone and Tamoxifen)

18.1.6.3.2. Hydroxyurea (arrest cell cycle and induce apoptosis)

18.1.6.3.3. Bevacizumab (antagonizes VEGF pathway)

19. Qb

19.1. Primary pediatric brain tumors

19.1.1. Astrocytoma, Medulloblastoma, Craniopharyngioma, Ependymoma, Germ cell tumors

19.2. Posterior fossa tumors in children

19.2.1. Pxa, Medulloblastoma, Ependymoma, Brainstem glioma

19.3. Highest incidence of metastas in children

19.3.1. Sarcoma