usmles1notes

[usmles1notes]

Resources for Primary Brain Tumors

https://step1.medbullets.com/oncology/113096/primary-brain-tumors

https://library.med.utah.edu/WebPath/CNSHTML/CNSIDX.html

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Children Brain Tumors

Most pediatric CNS tumors develop BELOW the tentorium cerebelli

INFRAtentorial CNS tumors can cause “cerebellar symptoms” (nausea/vomiting, gait problems, ataxia, impaired coordination)

INFRAtentorial tumors can cause obstructive HYDROCEPHALUS (due to obstruction of 4th ventricle)

Risk factors:

Exposure to ionizing radiation increases the risk of CNS tumors

Certain genetic syndromes increase the risk of pediatric CNS tumors (tuberous sclerosis, neurofibromatosis 1)

PILOCYTIC ASTROCYTOMA (named for “hairlike” projections on microscopy) (most common pediatric CNS tumor, almost always occurs in children)

Grade 1 (benign, unlike astrocytomas in adults [higher grade & aggressive])

Frequently contain activating mutations in the BRAF gene → activates abnormal cell growth

Well-circumscribed tumors; contain both solid and cystic components; composed of cells with long “hairlike” processes; long processes of tumor cells contain Rosenthal fibers (EOSINOPHILIC CORSKSCREW-shaped glial filaments)

Stains positive for GFAP (because they are glial tumors)

MEDULLOBLASTOMA (most common pediatric MALIGNANT CNS tumor)

Stain positive for SYNAPtophysin & NEURON specific enolase (because tumor originates from cells that are partially differentiated in the NEURONAL direction)

Can extend into the 4th ventricle (diamond-shaped CSF collection) --> intracranial hypertension (extension into 4th ventricle → obstructive hydrocephalus → ICH)

Some MEDULLOBLASTOMAS contain MYC amplifications

Soft friable tumors with areas of NECROSIS

Composed of sheets of small BLUE cells (due to hyperchromic nuclei and scant cytoplasm)

Homer-Wright ROSETTES (small BLUE cells surrounding acellular pink neuropil)

May produce “DROP metastases” (CSF contains malignant cells, tumor nodules form along spinal cord)

Ependymoma

CNS tumor that arises from cells lining the VENTRICULAR system [ependymal cells]

Most commonly grow from the roof of the 4th ventricle (diamond-shaped CSF collection) --> intracranial hypertension (extension into 4th ventricle → obstructive hydrocephalus → ICH)

In adults & neurofibromatosis type 2, EPENDYMOMAS occur along the SPINAL cord

Well-circumscribed tumors; contain both solid and cystic components; display PERIVASCULAR pseudorosettes (cells form a circle around blood vessels → grow long extensions toward the center); display ependymal rosettes (cancer cells cluster in an attempt to form a ventricle → ring of cells around an empty lumen)

Craniopharyngioma

Benign tumors arising from epithelial remnants of Rathke’s pouch [oral ectoderm that ultimately forms anterior pituitary] (most common SUPRAtentorial pediatric tumor)

Display solid, cystic, and calcified components

Primary CNS GERM cell tumors (extragonadal GERM cell tumors, result from abnormal migration of embryonal cells during development)

Pinealoma

The PINEAL gland is the most common location for CNS germ cell tumors (PINEALOMAS)

Primary CNS germ cell tumors are most commonly GERMINOMAS (similar to testicular SEMINOMAS)

Can cause obstructive HYDROCEPHALUS (due to impingement on cerebral aqueduct)

Can cause intracranial hypertension (due to obstructive hydrocephalus)

Can lead to Parinaud syndrome (vertical gaze palsy syndrome, presents with “setting sun sign”) (due to compression of the tectum & superior colliculi)

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Adult Brain Tumors

Adult CNS tumors are usually above the tentorium

MRI is useful for imaging of CNS

Risk factors:

Radiation

Genetic syndromes (tuberous sclerosis, neurofibromatosis 2, VHL syndrome, Turcot syndrome)

Metastases are the m/c CNS neoplasms (from lung cancer, breast cancer, and melanomas)

Metastases to the CNS usually:

Present at the grey-white junction of the brain

Display central necrosis

Glioblastoma Multiforme

M/c malignant, high-grade astrocytoma (GFAP positive)

M/c at age 30-50

M/c involve frontal and temporal lobes

“Butterfly glioma”: due to growth into the corpus callosum and across the midline

MRI: thick peripheral rim enhancement, small round purple cells that line up along bands of necrosis (”pseudopalisading necrosis”)

Microvascular proliferation can lead to hemorrhage

Oligodendrogliomas

Slow growing tumors (resembles oligodendrocytes)

M/c @ age 40-50

M/c common in the frontal and temporal lobes

Frequently calcified

“Fried egg” on histology: round nuclei with granular chromatin and generous cytoplasm

“Chicken-wire” appearance: networks of thin, fragile anastamosing capillaries

Meningioma

M/c F>M aged 40-60

Originating from arachnoid mater

Well-circumscribed, round tumor growing out from the dura

M/c at the dural folds (falx cerebri, tentorium cerebelli, venous sinuses)

Psammoma bodies (eosinophilic laminated calcium deposits); spindle cells in a whorled pattern

Does not invade

Hemangioma vs. hemangioblastoma

VHL genetic syndrome

predisposes to CNS and non-CNS tumors

VHL is autosomal dominant

VHL is caused by deletion of the VHL tumor suppressor gene on chromosome 3

VHL follows “two-hit hypothesis” (one inherited germline mutation, then a somatic mutation acquired during lifetime)

VHL is associated with clear cell RENAL carcinoma

VHL is associated with pheoCHROMOcytomas in adrenal medulla

Hemangioblastomas

VHL most commonly presents with hemangioblastomas (benign vascular lesions, occur in multiple CNS sites)

Affect the cerebellum & spinal cord (INFRAtentorial lesions) and the retina

Well-circumscribed vascular lesions

Surrounded by large fluid filled cysts (adds to compression of adjacent tissue)

Stain positive for periodic acid-Schiff (PAS), which stains polysacharride like glycogen, glycoproteins, etc.

Prone to rupture and subsequent hemorrhage (due to thin vascular walls)

Fairly normal capillary architecture (includes smooth muscle and elastic fibers) (in contrast to hemangIOMAS)

Hemangiomas

Retina can bleed → retinal edema, traction, and detachment

Very prone to hemorrhage (because vessels contain a single endothelial layer and thin adventitia [NO elastic fibers or smooth muscle])

Cavernous Hemangiomas

A type of blood vessel malformation or hemangioma, where a collection of dilated blood vessels form a benign tumor

Tumors common in CNS and liver, clusters of thin-walled, dilated blood vessels

Primary CNS Lymphoma

Neoplastic lymphocytes proliferate in the brain, instead of within lymphoid organ

An immunocompromised state is a significant risk factor for CNS lymphoma (most common CNS malignancy in this group)

CNS lymphoma in immunosuppressed patients is almost always associated with EBV infection

CNS lymphomas are diffuse LARGE B cell lymphomas 

CNS LYMPHOMAS tend to be multiple and accumulate around blood vessels

CNS LYMPHOMAS often display areas of necrosis

On MRI, CNS LYMPHOMAS demonstrate RING enhancement

Pituitary Adenoma

Benign overgrowth of one pituitary cell type

Suprasellar

Can cause bitemporal hemanioma

Schwannomas

Neoplasm of Schwann cells

Most common in peripheral nervous system, but can form in CNS

CN 7, 8 

Localized to CNS in internal acoustic meatus

@ cerebelllopontine angle

Loss of hearing/tinnuitsi

S100+

NF-2 associated

Bilateral tumor

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Brain Tumors

Adult tumors are often supratentorial; children tumors are infratentorial.