Brain Tumor 😶‍🌫️

Brain Tumor / CNS Tumor

• Prognosis
• Grade 1 → good prognosis
• Grade 4 → very bad prognosis

Basis of Grading (AMEN Mnemonic):

Grading Criteria:

General

• Treatment: Surgery, chemotherapy, radiotherapy

In children

• Most pediatric tumors:
• Infra tentorial.

• In adults:
• 2/3 are supra tentorial.

• Sequence in adults:
• Secondary > Meningioma > Glioma.

Brain Metastasis

• M/c cancer metastasizing to cerebrum: Lung cancer

• M/c cancer metastasizing to leptomeninges: Breast cancer

• Management:
• Radiotherapy (for multiple mets)
• Surgery (for solitary lesions)
• Steroids (DOC for vasogenic edema due to ↑ ICT)

Neural Tumor

Presentation

• Slow-growing

• Rubbery

• Non-tender swellings

Associated signs:

• Freckles and skin patches over face and trunk

Types of Neural Tumors

• Neurofibromas

• Schwannomas

• Ganglioneuromas

Common Locations

• Along peripheral nerves

• Can include the neck

Gamma knife (Stereotactic Radiosurgery (SRS))

• A type of Stereotactic Radiosurgery (SRS).

• Gamma rays are focused to ablate the lesion.

• Invented by neurosurgeon Lars Leksell.

• Uses the Leksell frame.
• Localized based on coordinates.

• Use Cobalt 60

• Used for localized cancers
• not with metastasis

• Used for
• Brain lesions:
• Vestibular schwannoma.
• Trigeminal neuralgia.
• AV malformations.
• Pituitary microadenoma.
• brain lesions that are inaccessible by surgery.

Cyberknife:

• Stereotactic Body Radiotherapy

• Uses LINAC and X-rays

• Advantage:
• Can be used for the rest of the body
• (unlike Gamma knife for the brain only).
• No frame is needed.
• Localised inaccessible lesions
• Cannot use for those with mets

• Ex: Inoperable Stage 1 Lung Tumor

• Mnemonic: Exes (X ray) Stand in Line (Linac) → and Cyberattack (Cyberknife) → Dont frame (No frame)

Clinical features of brain tumor

• Headache:
• Tension type.
• Worse in
• morning.
• Valsalva maneuver.
• bending forwards
• rising up from recumbent position.

• Altered mentation.

• Vasogenic cerebral edema
• Focal seizures.

• Speech defect.

• Gait abnormalities.
• Gait ataxia.

• Head tilt.

• Gaze abnormalities.

• Visual defect: Bitemporal hemianopia.

Diagnosis

• IOC: Gadolinium enhanced MRI.

Brain tumor with worst prognosis

• In Pediatrics:
• Brainstem glioma,
• Medulloblastoma,
• Cerebellar astrocytoma.

• In adults:
• Grade 4 glioma
• Glioblastoma multiforme.

Leptomeningeal metastasis

• Cause:
• Breast cancer.

• Identification:
• Gadolinium enhanced MRI.
• Lumbar puncture.
• CSF cytology: malignant cells

Specific Brain Tumors

Pilocytic Astrocytoma (JPA) / Juvenile Pilocytic Astrocytoma

• Occurrence: Seen in children.

• Radiological Features (CCC): 
• Cystic tumor in the cerebellum in a child.

• Mutations: 
• BRAF KIAA fusion or 
• BRAF B V600E mutation.

• Grade 1 (Pilocytic astrocytoma):
• M/c astrocytoma in children
• Presents as mural nodule
• Rx: Excision
• Prognosis: Very good → Grade 1 tumor.

• GFAP

• Glomeruloid bodies

Microscopically: 

• Shows thin pink fibers called Rosenthal fibers ("pylo" means hair-like).

• Mnemonic: Juvenile () home → Brats (BRAF 600) → children ()
• We gave them Rose (rosenthal) → They became good (good prognosis)

• Medulloblastoma → Child → Cerebellum → bad tumor

• Cystic BRAIN TUMORS
• Craniopharyngioma
• JPA

Marker	Positive In	Mnemonic / Note
Cytokeratin (CK)	Carcinoma	C for C
Vimentin	Sarcoma	ㅤ
CD45 / LCA Leucocyte Common Antigen	Lymphoma	L for L
HMB45 S 100	Melanoma	M for M
CD1A	Langerhans Cell Histiocytosis (LCH)	ㅤ
CD99	Granulosa Cell Tumor (ovary)	99-year-old granny
(MIC2)	Ewing Sarcoma (bone)	Mitu → childhood tumor
Glial Fibrillary Acidic Protein (GFAP)	Tumor markers in glioma (Astrocytoma, Glioblastoma multiforme)	ㅤ
Lamin	Progeria: Disorder of premature ageing (Hutchinson Gilford)	ㅤ

• Mnemonic:
• Sarcoma
• Vimal Sar
• Also remember Rape (Rhabdomyosarcoma) Syn (Synovial) Mnemonic
• Car
• Sit (Cytokeratin) inside Car
• Remember car → bike → took another route
• Helmet (HCC → Fibrolamellar)
• Rc book (RCC)
• Phone (Follicular CA)
• Granulosa cell tumor mnemonic
• 99 year old granny ex ne vilikkan poi.
• (99 (CD 99) year old granny → hyper estrogenism () → Called Ex (Call exner) → offered coffee (coffee bean) → she shouldve inhibited (inhibin) her)
• Ewings sarcoma Mnemonic:
• Mittu (MIC2) (11 year old) → Onion () kazhichapo wings () vannu → to Wings to Fly (EWS-FLI1) in Right (Homer wright) direction to get Pasta (Pas +ve).
• Mittu thirichu vannapo 22 vayassai (t(11:22))

Condition	Feature
NF1	Chromosome 17
NF2	Chromosome 22
DermatoFIBROSARCOMA protrubans	t (17;22)
Nodular Fascitis	t (22;17)

Glioblastoma (GBM)

• Occurrence: An adult tumor.

• Crosses corpus callosum, forming butterfly-shaped tumour

• Genetics:
• 90% IDH wild type.
• 10% IDH mutant.
• IDH mutations
• Mnemonic (IDH): I am EGOistic → so idichu (IDH)
1. Enchondroma
2. Glioblastoma
3. Oligodendroglioma

• Nature:
• Grade IV.
• Poor Prognosis

• Poor prognosis

• Gross App
• Butterfly glioma.

• Imaging/Microscopic Features:
• Serpentine necrosis.
• Pseudopalisading of tumor cells.
• Glomeruloid bodies

Radiology

• Mnemonic: Blasted across the midline

• Irregular borders, central necrosis.

• Butterfly Glioma.

• Crosses midline involving corpus callosum.

 

Meningioma

• Vividly enhancing, extra-axial lesion.

• Has Dural tail sign.

Rx:

• Surgery → f/b

• Radiotherapy;
• Oral temozolomide

• Chemoradiation
• Reserved for patients with residual tumor after surgery.

• Mnemonic:
• GLio → Gallilio with team (temozolomide) → Wild (wild mutant) life exploring for 4 (grade 4) days → Saw Butterfly () → Snake (serpent) ne kandu odi Pseudo Palaruviyil (pseudopalisade) chaadi → Marichu (poor prognosis) → body Gloat (Glomeruloid) cheyth kidannu
• Radioyil vannu

Medulloblastoma

• Occurs in a child in the cerebellum.

• Most common tumor in child

• Grade 4 tumor
• Bad prognosis
• Any brain tumor with “Blastoma” is bad in brain

• Shows pseudorosettes 

 

• Most common posterior fossa tumour in a child

• Highly cellular, appears hyperdense

• Medulloblastoma has bad prognosis.

• Can spread from brain to spinal cord (Cranio-spinal axis spread).
• Drop Mets

• Can cause obstructive hydrocephalus.

• Occupies 4th ventricle
• ⇒ 4th ventricle obstruction
• upstream hydrocephalus

Prophylactic Craniospinal Irradiation

• Indications: SMALL
• Cancer with high chance of spreading to spinal cord.
• Medulloblastoma
• Ependymoma
• ALL
• Small cell carcinoma Lungs

• First hormone deficiency after head & neck radiation:
• Growth hormone deficiency.

• Thyroid cancer due to radiation:
• Papillary carcinoma.

Germinoma

• Children are afraid of germs (Children → germinoma)

Oligodendroglioma

Blood Vessels: 
Shows chicken wire blood vessels.

Shows fried egg appearance 
(nucleus with a white area around it).

• Mnemonic:
• Oligodendroglioma → Old guy (119 years old → chromosome 1p and chr 19q)
• His brain calcified () →
• We buy him fried egg () and chicken ()
• and Idich (IDH)

• Most Common Mutation: 
• IDH mutations
• Mnemonic (IDH): I am EGOistic → so idichu (IDH)
1. Enchondroma
2. Glioblastoma
3. Oligodendroglioma

• Genetic Feature: 
• Co-deletion 1p19q (deletion of short arm of chr 1 + long arm of chr 19 together)
• Denotes good response to chemotherapy.

• Microscopically: 
• Shows fried egg appearance (nucleus with a white area around it).

• Blood Vessels: Shows chicken wire blood vessels.

• Radiologically: 
• Shows calcification.

Brain lesions with calcification

1. Craniopharyngioma

2. Oligodendroglioma

3. Meningioma.

4. Congenital CMV
• Periventricular calcification

5. Congenital Toxoplasmosis
• Cerebral calcification

6. Neurocysticercosis.

• Mnemonic: Brain calcifiy () → when Old (Oligodendroglioma) → start saying Meaningful (Meningioma) Crap (Craniopharyngioma)

NOTE: Chicken Wire Appearance, Fried egg, Diens and Mycoplasma

Pattern	Appearance Type	Condition/Location
Fried Egg	Hairy cell leukemia	Bone marrow biopsy
Fried Egg	Seminoma	Testis
Fried Egg	Dysgerminoma	Ovary
Fried Egg	Mycoplasma colonies	Microbiology
Fried Egg colonies on SDA with Olive Oil	Malassezia furfur	Fungus
Chicken Wire	Chicken wire blood vessels.	Oligodendroglioma
Chicken Wire	Chicken wire calcification	Chondroblastoma (bone tumor)
Chicken Wire	Chicken wire blood vessels	Mucinous/Colloid carcinoma of the breast → FNAC
Chicken Wire	Chicken wire fibrosis	Alcoholic liver disease (liver pathology)

• Mnemonic:
• We cannot eat fied egg because it has
1. Fur ()
2. Hair ()
3. Germs (dysgerminoma)
4. Semen (seminoma)
5. Blood (Mycoplasma) in it

• Mnemonic:
• Chicken Breast piece (Breast Ca) um cartilage (Chondroblastoma) um Kallum (Colloid carcinoma, Alcoholic LD)

Mnemonic:

• for Mycoplasma
• Atypical Walking (walking pneumonia) people (PPLO agar) with CAT (Cold agglutination test) → Eat (Eaton agent) fried egg (fried egg colonies) and Dine (Diens stain) → No walls (cell wall deficient) and take steroids (steroid in cell membrane)

• for Diens
• Diens phenomenon → Proteus
• Diens stain → Mycoplasma

Ependymoma

• Origin: 
• Arises from ependymal cells of ventricles
• CSF-producing cells

• Most Common Site:
• In children: Fourth ventricle.
• In adults: Spinal cord.

• Associated with: 
• NF2

• Microscopically: 
• Shows perivascular pseudorosettes 
• cells arranged around a central blood vessel

• New Variant (INIC):
• RELA fusion ependymoma
• RELA gene.
• Chromosome 11
• Ependymoma
• Above Tendorium (supratendorial)

• Mnemonic: EEppan () Valya thendi (above tendorium) anu → 4th (4th ventricle) il 11 year (chr 11) old kuttikk psudo rose () koduthu → avalde relay (rela fusion) poi

• Homer Wright rosettes or pseudomedullary rosettes
• Center → filled
• Mnemonic: Psudo friends → hide something inside their heart

 

• Flexner Winterstener Rosette
• Center → Pale or white
• Mnemonic: True friends wants what is good for you → heart (centre) is pure white
• Found in small round blue cell tumor

• Homer-Wright → pseudo rosettes.

• Mnemonic: MEN () R () Wright () and Men are Pseudo, Men are Blast
• Medulloblastoma
• Ewings/Ependymoma
• Neuroblastoma
• Retinoblastoma
• (Both rosettes → seen in Retinoblastoma).

Meningioma

Psammoma Bodies

Whorling of tumour cell

• Occurrence: 
• More common in females.

• Arise as a complication of therapeutic radiation.

• Clinical History: 
• Often related to pregnancy (tumor increases) or 
• menstruation (headaches) → indicates hormonal influence.

• Receptor Status: 
• Progesterone receptor positive.
• ↑ Rapidly in size throughout pregnancy

• Associated with: NF2.

• Location: 
• Arises from the meninges → dura (outside brain parenchyma).
• Cell of origin for meningioma:
• Arachnoid capsules.
• Extra-Axial brain tumor.

• Radiology: 
• Dural tail sign.
• Sunburst appearance of blood vessels (contrast).

• Microscopically:
• Whorling: 
• Tumor cells arranged round and round in circles.
• Psammoma bodies: 
• Calcium bodies arranged round and round.

• NCCT
• Intracranial calcification.

• Mnemonic: Females nu vaalundu (dural tail sign), pregnant (related to pregnancy), menstruate (related), progesterone (progeserone receptor positive) → like men (meninges), verthe karangum (whorling) → last ammumma (psammoma) avum → calcified mind (intracranial calcification)

Atypical Teratoid/Rhabdoid Tumor (ATRT)

• Mutation: Associated with SNF (SNF5) or INI gene mutations.

• Mnemonic (Rabies/Dog Sniffs): 
• Rabdtoid (rabies virus) → rabies dog sniffs → SNF mutation and INI gene.

DNET (Dysembryoplastic Neuroepithelial Tumor)

• Microscopically: 
• Characterized by floating neurons in pools of mucin 
• (watery, fluidy background).

• Mnemonic: The Net (DNET)→ Fish Float → neuron float (Neuron float)

Vestibular schwannoma /Acoustic neuroma

• Nerve tumor
• Originates from inferior vestibular nerve.
• In internal auditory canal.

• Grows towards cerebellopontine region.

• Most common: Unilateral.

• Associated with: NF2 syndrome.
• Bilateral seen in neurofibromatosis type 2.

Symptoms:

• Transient vertigo.

• Earliest
• Absent corneal reflex
• 5th nerve affected 1st

• M/c
• Unilateral SNHL.
• Retro cochlear hearing loss.

• Tinnitus is absent.

• Hitzelberger sign:
• Vestibular schawannoma → Sensory fibers of 7th nerve
• loss of sensation in concha and along posterior meatal wall
• Mnemonic: HitZel → Hit Zeven → 7th CN → Hit Antony

• 9th, 10th, 11th nerves
• Dysphagia, palatal paralysis, speech difficulty

• Brunss nystagmus
• Suggests large CPA tumor
• Different nystagmus on right vs left gaze
• Gaze toward lesion side
• Coarse
• Low frequency
• High amplitude
• Vestibular type
• Gaze away from lesion
• Fine
• High frequency
• Low amplitude
• Gaze-evoked (central) type

Microscopically:

• Antony A areas: 
• Hypercellular (lot of cells).

• Antony B areas: 
• Hypocellular/blank (hardly any cells).

• Verocay bodies: 
• Two rows of palisading nuclei with cytoplasm in the center.

• Mnemonic:
• Antony A → ahankaram kuduthal (↑cellularity) and show (shauman) karanam → veruthu (verucay) pallu (palisading) adichilakki
• apo show ahankaram kurach (↓ cells) antony b () ayi

Diagnosis:

• MRI with contrast (IOC)

• B/L ice cream cone appearance in cerebellopontine angle.
• B/L Vestibular schwannoma.

• Chromosome no. 22.

• Mnemonic: Show man () eating Ice cream () with 22 (Chr 22) year old

Treatment:

• <3cm: Radio surgery.

• >3cm: Surgical excision/Gamma knife

NF2 Associated Brain Tumors

Lymphoma of the Brain

Angiocentric pattern: Tumor cells arranged around blood vessels.

Hooping pattern: Reticulin fibers cover/hoop the tumor cells.

• Occurrence: Usually seen in HIV positive patients.

• Type: A B cell lymphoma (DLBCL).

• Microscopically (Two patterns):
• Angiocentric pattern
• Tumor cells arranged around blood vessels.
• Hooping pattern
• Reticulin fibers cover/hoop the tumor cells.

• Mnemonic: Lymphoma → Lymph scoop (hoop) cheyth edth from Blood vessel (Angiocentric)

Diffuse Midline Glioma

• Prognosis: 
• Has a poor prognosis.

• Genetics: 
• A/w H3 K27M mutation 
• involving a histone protein H3

• After Galilio (Midline Glioma) died → His stone (Histone H3) was made everywhere → His Heart ka Muscle (HKM) took for …

• Glioma occurring in the midline of the brain and is diffuse.

Miscellaneous Images/Diseases

Craniopharyngioma

• Rare, but is supratentorial paediatric brain tumor.
• Situated near pituitary.
• Occurs in the suprasellar region of the brain, near the optic chiasm.
• Related to Rathke's pouch.

• Clinical presentation:
• Short stature.
• Central DI: Polyuria, polydipsia.
• Visual defect
• Bitemporal hemianopia
• NOTE: same in adults: Prolactinoma

MRI head:

Cystic with calcification

• Cystic tumor with
• machinery oil consistency and
• intracranial calcification.

 

Feature	Craniopharyngioma	Pituitary adenoma
Age	More common in child	-
Vision 1st	inferolateral bitemporal hemianopia	superolateral bitemporal hemianopia
Sella Turcica	-	Widened
Location	Center/midline, suprasellar	Intrasellar
Appearance	-	Figure of 8 appearance Primary pituitary macroadenoma
Calcification	Present	-
Components	[Cystic components] Peripheral palisading Stellate reticulum Wet keratin ↳ brown "machine oil" kind of fluid	ㅤ

Microscopically:

• Peripheral palisading: Cells at the periphery arranged in a single line.

• Stellate reticulum: Loose, "roaming" cells.

• Wet keratin: Pink material
• brown "machine oil" kind of fluid during surgery → actually wet keratin.

• CP → Carrrot pudding cake → palisading chocolate above → nuts in b/w (stellate reticulum) loosely → inside pink cream (Wet keratin)

Variant Creutzfeldt Jacobs Disease (VCJD)

Clinical Features

• 30-year-old man presented with complaint of myoclonic jerks + dementia.

• Myoclonic jerks may be produced in response to loud sound:
• Startle myoclonus.

• History suggests consumption of poor-quality beef
• eating tainted beef/ infected beef with prions.

• Transmissible Spongiform Encephalopathy (TSE).

• Bovine spongiform encephalopathy
• Spongiform vacuolations brain
• Prion → Praani () infected a Kuru () → made it spongy (spongy vacuolations) like → we took it to congo (congo red) and Passed (PAS) it to them

Pathology

• Prion disease (prion particle - smallest infectious particle).

• Prion: Protein coat only, no DNA/RNA.

• Resistant to 121°C heat.

• Kill by 134°C for 1.5 hrs (Autoclaving)

• Source: Tainted beef

• Has a long incubation period

• Prion particles → enter the GIT → enter blood stream → cross the blood brain barrier.

• PrPC → PrPSC is the abnormal folded protein
• accumulates as β Pleated structures

• start accumulating in the cytoplasm of neurons
1. Cause neurodegeneration
• dementia
2. Abnormal firing of neurons
• results in myoclonic jerks

Manifestations:

• Myoclonic jerks
• startle myoclonus

• Dementia.

• Gait ataxia.

• Incapacitation / Bedridden.

• Death due to pneumonia in Parkinsonism, Alzheimer's, VCJD.

MRI head:

• Increased intensity of basal ganglia

• Cortical Ribboning

• Hockey stick sign → Pulvinar Nucleus of thalamus

• Hockey stick sign seen in:
• In MRI: VCJD
• In ECG: Digoxin.
• In Echo: Mitral stenosis.
• In OBG: USG Abdominal circumference

CSF Examination

• Shows protein 14.3.3

EEG Finding

• Periodic sharp wave complexes.
• Keyword in MCQ, to identify VCJD
• Mnemonic:
• Variant = Periodic
• Crude = Sharp

Important Information

• Periodic lateralized epileptiform discharge (PLED)
• is seen in HSV encephalitis.
• Mnemonic: His wife → Period late → she seizures

Prion Diseases

• Sreelankan (Gerstman Schlankler Syndrome) cannibals (Kuru ds) sleep (familial fatal insomnia)

• Variant Creutzfeldt-jakob disease.

• Classical Creutzfeldt-jakob disease.
• From Human GH Inj → Prev taken from cadaveric pituitary
• Human to human transmission
• Not todays world

• KURU Disease
• (Cannibals).
• Specifically shows Kuru's plaque.
• Positive for Congo red and PAS

• Familial fatal insomnia.

• Gerstman Schlankler Syndrome.
• Disease 4 & 5 are genetic (Chromosome 20 defect).