Brain tumors — Medicine Library

Summary

Brain tumors are masses of abnormal cells within the brain. They can be primary or metastatic, benign or malignant. Common tumors in children are pilocytic astrocytomas, medulloblastomas, ependymomas, and craniopharyngiomas. The most common brain tumors in adults are glioblastomas, meningiomas, hemangioblastomas, schwannomas, oligodendrogliomas, and pituitary adenomas. Clinical features and radiological findings vary according to the type, location, and onset of the tumor. Magnetic resonance imaging (MRI) is the primary diagnostic method. The histological grade of the tumor is an important factor in determining the prognosis. Removal of the entire tumor is a prerequisite for remission. Malignant tumors usually require additional treatment with radiotherapy and/or chemotherapy.

Meningiomas, pituitary adenomas, schwannomas, and neoplastic meningitis are discussed in separate articles.

Epidemiology

Approx. 30% of brain tumors are primary brain tumors, while approx. 70% are metastases.
Approx. 40% of primary brain tumors are benign.
Sex: ♂ > ♀ (except meningiomas, which occur more frequently in women) [1]

Epidemiological data refers to the US, unless otherwise specified.

Approach

Initial evaluation [2]

Clinical assessment

Obtain a thorough patient history and neurological examination.
Suspect a
brain
tumor in patients with clinical features including:
- Headaches (especially with headache red flags)
- Other signs of elevated intracranial pressure (ICP), e.g., papilledema
- New onset seizures [3]
- Focal neurological deficits; depending on tumor location, e.g., sensory deficits
- Nonfocal neurological deficits
- Cognitive, behavioral, and personality changes

Symptom onset in patients with primary brain tumors is usually insidious, while symptom onset in patients with brain metastases is typically acute or subacute.

Diagnostic testing

Obtain
neuroimaging.
- Gadolinium-enhanced MRI head: preferred
- CT head and neck with IV contrast: if MRI is not possible
Further testing depends on imaging findings.
- Findings suggestive of primary brain tumor: Consult neurosurgery for diagnostic confirmation, e.g., via brain biopsy or resection
- Findings suggestive of
  metastatic brain tumor
  - Initiate diagnostics of cancer of unknown primary.
  - Obtain biopsy of the brain metastasis if primary is not identified. [4]

Overview of MRI findings in brain tumors

There is significant overlap between MRI findings in common primary brain tumors (e.g., gliomas) and brain metastases.
Brain tumors typically appear hypointense to isointense on T1-weighted images and hyperintense to isointense on T2-weighted images.

Overview of MRI findings in brain tumors
	MRI findings
Tumor type	Typical location	Other findings
Pilocytic astrocytoma [5]	Cerebellum or optic nerve	Intense, heterogeous contrast enhancement of solid portion; cyst wall typically non-enhancing Round or oval, well-demarcated, contrast-enhancing lesion within a larger, cystic lesion
Anaplastic astrocytoma [6]	Variable	Nodular enhancement typically seen Heterogeneous lesion with perifocal vasogenic edema No necrosis (in contrast to glioblastoma)
Glioblastoma multiforme [7]	Variable	Contrast enhancement usually present Localized multifocal garland-like enhancements with a hypointense necrotic core may be seen.
Primary CNS lymphoma [8][9]	Periventricular	Homogeneous enhancement; ring contrast enhancement may be present Relatively little edema
Meningioma [10]	External surfaces of brain; within ventricular system	Homogeneous enhancement Round, sharply demarcated lesions Thickened dura mater
Metastasis [11][12][13]	Gray-white matter junction and/or watershed areas of the arterial system; often, multiple nonlocalized lesions	Well-circumscribed Large metastases: ring enhancement due to central necrosis Small metastases: homogeneous enhancement More likely to be hemorrhagic than primary brain tumors Edema extensive relative to tumor size

Cerebellar pilocytic astrocytoma Low-grade glioma Garland-like enhancement in glioblastoma Glioblastoma multiforme (WHO grade IV astrocytoma) Bilateral glioblastoma (butterfly glioma) Ring-enhancing lesions in the brain Dural based mass Meningioma Cerebral metastasis in lung carcinoma 1/2

Management

Principles of treatment

Management should be specialist guided; utilize a multidisciplinary approach and consult a tumor board if available.

Management of
metastatic brain tumor
- Identify and treat primary malignancy.
- See “Brain metastases” for details on treatment options.
Management of primary
brain
tumor
- Based on both tumor and patient characteristics
- May include:
  
  Maximal safe surgical resection
  
  Radiation therapy: e.g., standard fractionated external beam radiation therapy
  
  Systemic therapy: e.g., chemotherapy, cancer immunotherapy
- Offer clinical trial enrollment and consider palliative care for patients with high-grade tumors (e.g., glioblastoma multiforme).

Management of complications of brain tumors [2]

See also ”Cancer-related complications” and “Cancer treatment-related complications.”

Venous thromboembolism (
VTE)
[14][15]

Consider pharmacological VTE prophylaxis for select patients.

Offer therapeutic anticoagulation for patients with VTE (LMWH is the preferred agent).

Patients with brain tumors are at increased risk of intracerebral hemorrhage; use shared decision-making for anticoagulation treatment decisions.
Seizures
[16][17]

Primary prophylaxis is not recommended.

Secondary prophylaxis (i.e., history of seizures): Initiate treatment of epileptic seizures. [18]
Vasogenic cerebral edema
- Administer glucocorticoids (e.g., dexamethasone ) for patients with signs of elevated ICP. [19][20]
- Follow local treatment protocols when available.

Certain types of metastatic brain tumor (e.g., melanoma, renal cell carcinoma) are more likely to hemorrhage, but are not an absolute contraindication to therapeutic anticoagulation. [16]

Taper and discontinue perioperative prophylactic medications within 7–10 days of surgery, unless otherwise indicated. [2]

**Cerebellar pilocytic astrocytoma**
MRI head (a: T1-weighted; with contrast; sagittal plane; b: T2-weighted; axial plane) of a child
A large lesion in the right cerebellar hemisphere displaces the vermis to the left of midline. It has a large cystic component (T1 hypointense and T2 hyperintense; red overlay) and a heterogeneously enhancing solid nodular component (green overlay).
Cerebellar pilocytic astrocytoma frequently manifests as a large cystic lesion with an enhancing mural nodule.

Source: “Figure 1, in: The Journal of Headache and Pain” by Irene Toldo, Debora De Carlo, Rodica Mardari et al., The Journal of Headache and Pain, licensed under CC BY 2.0. Modifications: - Labels have been removed from original image (asterix and two arrows). - letters edited. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Low-grade glioma**
MRI head (top left: T1-weighted, axial plane; top right: T2-weighted, axial plane; bottom left: T1-weighted, with contrast, axial plane; bottom right: T1-weighted, with contrast, coronal plane)
There is a large, well-defined mass in the right frontal lobe (green overlay), which demonstrates hypointense signal on the T1-weighted images and hyperintense signal on T2-weighting with no significant surrounding edema. No significant enhancement is demonstrated on the post-contrast sequences.

Source: © IMPP

**Bilateral glioblastoma (butterfly glioma)**
T1-weighted contrast-enhanced MRI, frontal view: bihemisphere garland-like contrast enhancement. There is peripheral contrast agent enhancement (blue overlay) with central necrosis (green overlay). The third ventricle (arrowhead) is centrally located. The tumor is displacing the posterior horn of the lateral ventricle (red overlay). Diagnosis: bilateral glioblastoma (butterfly glioma).

Source: © IMPP

**Garland-like enhancement in glioblastoma**
MRI head (top: T2-weighted; middle: T1-weighted without contrast; bottom: T1-weighted with contrast; axial plane)
A heterogeneous lesion in the left frontal lobe distorts the interhemispheric fissure (indicated by white arrowhead). On the T1-weighted sequences, the lesion is predominantly hypointense (green overlay) with garland-like enhancement (yellow overlay). Associated edema is hyperintense on the T2-weighted sequence (red overlay).

Source: © IMPP

**Glioblastoma multiforme (WHO grade IV astrocytoma)**
MRI brain (T1-weighted; with contrast; axial plane) of a 69-year-old patient with personality changes and left-sided hemiparesis.
In the white matter of the right hemisphere, there is a large, poorly circumscribed space-occupying lesion, which is hypointense centrally (green overlay) with strong peripheral contrast enhancement (red overlay). The lesion is surrounded by edema (white overlay), suggesting rapid growth and displacement of surrounding structures. The mass effect has also caused a slight midline shift to the contralateral side (white dashed line), and compression of the right lateral ventricle (white arrowheads indicate anterior horn compression).
These radiographic features are typical of a glioblastoma.

Source: © IMPP

**Ring-enhancing lesions in the brain**
MRI head (A and B: T1-weighted, with contrast; C: FLAIR; axial plane) of a patient with HIV-associated primary CNS lymphoma
Ring-enhancing lesions in the right thalamus (A) and left frontal lobe (B) have central, low-signal intensity (hatched green overlay), suggesting necrosis. Hyperintense edema (green overlay) surrounds both lesions on the FLAIR sequence. Prominent sulci and ventricles reflect mild, generalized cerebral volume loss.
Toxoplasmosis and primary CNS lymphoma in patients with HIV/AIDS can have similar appearances, and further workup is needed if MRI cannot distinguish between them.

Source: “Fig. 1, in: An unusual and challenging case of HIV-associated primary CNS Lymphoma with Hodgkin-like morphology and HIV encephalitis” by Isaac E. Lloyd, Parker W. Clement, Karen L. Salzman, Randy L. Jensen, Mohamed E. Salama & Cheryl A. Palmer, Diagnostic Pathology, licensed under CC BY 4.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Dural based mass**
MRI head (T1-weighted; with contrast; sagittal plane)
There is a well-circumscribed homogeneous mass (green overlay) along the cerebral convexity. It demonstrates intense, homogeneous enhancement, equivalent to that of adjacent dura mater. Displacement without invasion of the surrounding white matter supports an extra-axial location.
This is a case of meningioma, a dural-based tumor. The dura is represented in this image by the thin, discontinuously enhancing line covering the inner surface of the skull (indicated by arrowhead).

Source: © IMPP

**Meningioma**
Cranial MRI, axial view (T1-weighted; with contrast)
Round, sharply delimited, homogeneously enhancing, hyperintense lesion (snowball appearance) in the interhemispheric region of the frontal lobe (green overlay).
The lesion displaces brain tissue. The dura is connected to the meninges of the frontal bone (dural tail sign) by a thick, hyperintense strand. A thin rim separates the lesion from surrounding brain parenchyma (CSF cleft sign).
These are characteristic radiologic features of a meningioma.

Source: “MeningiomaMRISegmentation” by Rkikinis, Wikimedia Commons, licensed under CC BY-SA 3.0. Modifications: cropped image. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Cerebral metastasis in lung carcinoma 1/2**
MRI head (T1-weighted; without contrast; axial plane) of a patient with lung carcinoma
A solitary, well-circumscribed, predominantly hypointense mass (hatched overlay) in the left occipital lobe is accompanied by perifocal edema (green overlay).
The lesion is consistent with a cerebral metastasis.

Source: © IMPP

**Cerebral metastasis in lung carcinoma 2/2**
MRI head (T2-weighted; without contrast; axial plane) of a patient with lung carcinoma
A solitary, well-circumscribed, predominantly hyperintense mass (hatched overlay) in the left occipital lobe is accompanied by perifocal edema (green overlay).
The lesion is consistent with a cerebral metastasis.

Source: © IMPP

Primary brain tumors

Classification

Primary brain tumors arise within the CNS and are classified based on the growth characteristics and cell type from which the tumor arises.

By the spreading potential

Types of brain tumors by growth characteristics
	Low-grade brain tumors	High-grade brain tumors
WHO grade	I–II	III–IV
Borders	Well-defined	Poorly-defined
Spreading potential	Low	High
Recurrence	Rare	Frequent

By the cell type

Gliomas (e.g., astrocytomas and oligodendrogliomas)
Choroid plexus tumors (e.g., choroid plexus papilloma, choroid plexus carcinoma)
Neuronal and mixed neuronal-glial tumors (e.g., paraganglioma, central neurocytoma)
Meningiomas (see “Classification of meningiomas”)
Embryonal neuroectodermal tumors (e.g., medulloblastoma: , CNS neuroblastoma)
Pituitary tumors: a group of tumors that arise from the pituitary gland (e.g., pituitary adenoma, craniopharyngioma)
Pineal tumors
Tumors of the cranial and paraspinal nerves (e.g., schwannoma: , neuroma, neurofibroma)
Mesenchymal nonmeningeothelial tumors (e.g., hemangiomas, hemangioblastoma, lipoma, hamartoma)
Germ cell tumors (e.g., teratoma)
Primary central nervous system lymphoma (PCNSL)

Metastasis

Primary CNS tumors do not metastasize to organs outside the CNS.
Drop metastases (intradural extramedullary spinal
metastases
) and leptomeningeal metastases may occur. [21]

Typically manifest as nodules along the spine and cauda equina that can cause back pain with neurologic symptoms (e.g., limb weakness)

Can be detected by lumbar puncture

Astrocytoma

Overview

Astrocytomas are neuroepithelial tumors (gliomas) that arise from astrocytes, which are a specific type of glial cell.

Classification of astrocytomas
Grade	Type	Description	Epidemiology	Location	Prognosis
I	Pilocytic astrocytoma	Slow growing, localized tumors Often associated with neurofibromatosis type I	Predominantly in children and young adults (< 20 years)	Cerebellum (most common) Cerebral hemispheres (supratentorial)	Favorable; long-term survival Completely curable with complete surgical resection Median survival: > 10 years
II	Diffuse astrocytoma	Slow growing, low-grade tumor that has the potential to progress to higher-grade tumors	Peak age: 20–40 years of age	Cerebral hemisphere	Incurable Median survival: 2–12 years
III	Anaplastic astrocytoma [22][23]	A slow-growing, infiltrative tumor that arises from glial cells in the CNS	Peak age: 30–50 years of age	Cerebral hemisphere	Incurable Median survival between 18 months and 10 years
IV	Glioblastoma multiforme (GBM) [24][25][26]	Malignant tumor with rapid growth, abrupt symptom onset, and short disease course (death within weeks)	Peak age: 60–70 years of age Most common malignant primary brain tumor	Cerebral white matter Possibly bilateral: butterfly glioma	Incurable Median survival of 15 months

Cerebellar pilocytic astrocytoma Low-grade glioma Garland-like enhancement in glioblastoma Glioblastoma in the temporal lobe Bilateral glioblastoma (butterfly glioma) Typical locations of brain tumors

Pilocytic astrocytoma [27][28][29][30]

Description: slow-growing, circumscribed, non-invasive tumor
Epidemiology
- Most commonly affects children and young adults (< 20 years)
- The most common primary brain tumor of childhood
Associated conditions: neurofibromatosis type I
Typical location
- Cerebellum (most common)
- Cerebral hemispheres (supratentorial)
Clinical features
- Insidious onset and slow progression of symptoms
- Vomiting
- Ataxia
- Failure to thrive
Diagnostics
- MRI findings
  - Well-demarcated cystic lesion
  - Bright contrast-enhancing solid nodule in the wall of the cyst
- Histopathology
  - Microcysts
  - Bipolar cells; hair-like projections
  - Eosinophilic fibers with corkscrew appearance (Rosenthal fibers)
Treatment: Surgical resection
Prognosis
- Favorable prognosis: high rates of long-term survival
- Curable with complete resection of the tumor
- Median survival: > 10 years

Cerebellar pilocytic astrocytoma

Optic glioma [31]

Description
- Low-grade, slow-growing tumor that arises from the glial cells of the optic pathway
- Typically a grade I pilocytic astrocytoma
Epidemiology: most frequently in children (< 10 years)
Associated conditions: neurofibromatosis type I
Clinical features
- Insidious onset and slow progression of symptoms
- Proptosis
- Strabismus
- Asymmetric nystagmus
- Impaired vision (in case of chiasmal involvement)
Diagnostics
- Fundoscopy findings: retinal pallor, papilledema
- MRI findings: thickening of the optic nerve or optic chiasm; suprasellar mass
Treatment
- No treatment in asymptomatic patients with no signs of tumor growth
- Surgical resection
- Radiotherapy
  - Unresectable tumors, e.g., chiasmal or optic tract lesions in optic glioma
  - Adjuvant to surgery
Prognosis
- Favorable; high rates of long-term survival
- Many patients have long-term visual impairment.

Diffuse astrocytoma

Description: slow-growing, infiltrative tumor that arises from glial cells in the CNS and has the potential to progress to higher-grade tumors
Epidemiology: peak age 20–40 years
Location: cerebral hemispheres
Clinical features
- Insidious onset and slow progression of symptoms
- Initially manifest with nonspecific features such as headaches, seizures
- Focal symptoms may develop (e.g, progressive paralysis, aphasia)
Diagnostics
- CT: hypodense lesion with no contrast enhancement
- MRI
  - T1 hypointense or isointense
  - T2 hyperintense
Treatment
- Complete surgical resection is often not possible. resection until definable margins can be attempted
- Percutaneous radiotherapy for very diffuse, unresectable tumors
Prognosis: incurable; median survival: 2–12 years

Anaplastic astrocytoma [22][23]

Description: A high-grade infiltrative tumor with variable rates of growth that arises from glial cells in the CNS
Epidemiology: peak age 30–50 years of age
Clinical features
- Headache
- Seizures
- Focal neurologic deficits
- Altered mental status
Diagnostics
- MRI
  - Inhomogenous lesion with perifocal edema
  - No necrosis (in contrast to glioblastoma)
- CT
  - Hypodense lesion with variable contrast enhancement
  - Positive mass effect
Treatment
- Tumor debulking through surgery. However, complete surgical resection is not possible.
- Percutaneous radiotherapy/chemotherapy
Prognosis: incurable; median survival between 18 months and 10 years

Glioblastoma multiforme

Description: : a highly malignant tumor derived from glial cells (e.g., astrocytes)
Epidemiology
[32]
[33][34]

Most common malignant brain tumor

Accounts for approx. 16% of all CNS neoplasms

♂ > ♀ (1.6:1)

Peak incidence: 64 years of age

Primary glioblastoma (∼ 90%): more frequent in elderly patients (6^th decade of life)

Secondary glioblastoma (∼ 10%): affects primarily younger patients (4^th decade of life)
Etiology
- Environmental factors: ionizing radiation
- Genetic or
  chromosomal factors
  [33]
  
  Primary glioblastoma: arises de novo
  
  EGFR overexpression
  
  PTEN gene mutations [35]
  
  Loss of chromosome 10q
  
  Secondary glioblastoma: arises from a preexisting low-grade tumor (e.g., diffuse astrocytoma, anaplastic astrocytoma)
  
  Isocitrate dehydrogenase 1 (IDH1) mutations
  
  p53 gene mutations
  
  Loss of chromosome 19q
Associated conditions: rare occurrence of glioblastoma in patients with certain genetic syndromes (e.g., type I and II neurofibromatosis, tuberous sclerosis, Li Fraumeni syndrome, Turcot syndrome)
Classification: The
2016 WHO classification groups
glioblastomas mainly on the basis of
IDH mutation status. [36]

IDH-wildtype glioblastoma (∼ 90%): usually corresponds with the clinically defined primary glioblastoma

IDH-mutant glioblastoma (∼ 10%): usually corresponds with the clinically defined secondary glioblastoma
Clinical features
- General clinical features of brain tumors (e.g., signs of ↑ ICP, seizures, focal neurologic symptoms)
- Short disease course with death within weeks (Rapid tumor growth)
- Apoplectic glioma: mimics intracranial hemorrhage and manifests with signs of ↑ ICP
Typical location
- Primary
  glioblastoma
  - White matter of the cerebral hemispheres (supratentorial)
  - Possibly bilateral, crossing the corpus callosum: butterfly glioma
- Secondary glioblastoma: frontal lobe
Diagnostics
- Characteristic features on
  MRI and CT
  - Irregularly shaped, inhomogeneous mass
  - Perifocal vasogenic edema
  - Mass effect: midline shift, ventricular distortion
  - Possibly hemorrhage
- MRI (
  gadolinium-enhanced)
  
  Garland-like, enhanced margins with a hypointense necrotic core
  
  T1 hypointense
  
  T2 hyperintense
  
  May also have multifocal enhancements
- Contrast-enhanced CT: irregular, heterogeneous enhancement of the margins and hypointense center
- Evaluation of IDH mutation status (via immunohistochemistry or genome sequencing)
- Biopsy
  - Dense, pleomorphic anaplastic cells that form pseudopalisades due to central necrosis or hemorrhage
    
    A histopathologic finding characterized by elongated nuclei stacked in rows that often radiate away from a central area of necrosis
    
    Classically associated with glioblastoma multiforme
  - Microvascular proliferation
  - GFAP positive
Treatment
- Surgical resection
- Palliative radiochemotherapy with temozolomide
- Adjuvant chemotherapy with temozolomide
- Glucocorticoids
- After recurrence
  - Reresection, temozolomide, and/or radiation (if tolerated)
  - The use of other chemotherapeutic agents (carboplatin, etoposide, irinotecan, nitrosoureas) can be tried as single agents or in regimens.
  - Bevacizumab
  - Tumor-treating fields (TTFields) [37]
    
    Noninvasive treatment modality based on the transcutaneous delivery of alternating intermediate-frequency and low-intensity electric fields to disrupt tumor cell division and inhibit tumor growth
    
    The electric field interferes with cancer cells in a number of ways, including the alteration of cell membrane polarization and inhibition of microtubule polymerization.
    
    Can be given in combination with adjuvant chemotherapy (e.g., temozolomide)
Prognosis
[33]
- Median survival: 15 months
- Positive prognostic factors: IDH-mutant glioblastoma, lower patient age, higher Karnofsky performance score, accessible tumor location for surgery
- Negative prognostic factors: large tumor size (> 5–6 cm), midline-crossing tumors

Glioblastoma in the temporal lobe Bilateral glioblastoma (butterfly glioma) Mass effect from glioblastoma multiforme (WHO grade IV astrocytoma) Garland-like enhancement in glioblastoma

Glial fibrillary acidic protein (GFAP) is an important diagnostic marker for astrocytomas; it is almost always positive in glioblastoma multiforme!

Brainstem glioma [38]

Description: a tumor arising from the glial cells in the brainstem that may be low-grade (I-II) or high-grade (III-IV)
Epidemiology: peak age 3–10 years
Clinical features
- Vomiting
- Cranial nerve deficits
- Ataxia
- Hydrocephalus
- Upper motor neuron signs
Diagnostics:
MRI
- No contrast enhancement
- T2 hyperintense lesion
Treatment
- Radiation and/or chemotherapy
- Surgical resection is often impossible
Prognosis
- Poor, especially in diffuse pontine gliomas
- Median survival: ∼ 10 months

**Glioblastoma in the temporal lobe**
Frontal section of a macroscopic brain preparation: There is a tumorous lesion with a macroscopic typical "colorful cut surface" in the temporal lobe. The yellow areas are necrosis and the marked white areas are cell dense regions. The surrounding red marked areas most likely correspond to the margin of a vessel or hemorrhage. The findings correspond to a glioblastoma.

Source: © IMPP

**Astrocytoma**
Upper row: axial native CCT scan. Lower row: axial CCT with contrast medium. Finding: grade II (diffuse) astrocytoma in the frontal lobe

Source: © IMPP

**Glioblastoma**
Photomicrograph of the brain (H&E stain)
Diffuse infiltration of the central nervous tissue by astrocytic tumor tissue can be seen. Palisade-like deposits of tumor cells with hyperchromatic, polymorphic nuclei surround the anuclear necrotic lesions. There are numerous mitotic figures. There is an abundance of capillary bundles with a hyperplastic endothelium. The tissue shows extensive, regressive changes.
Diagnosis: glioblastoma (WHO grade IV)

Source: © IMPP

**Pilocytic astrocytoma**
Photomicrograph of cerebellar tissue (H&E stain)
There are numerous bipolar cells, composed of a central basophilic nucleus with eosinophilic pilocytic processes (examples indicated in green) arising from either end. The pilocytic processes are arranged in bundles, which resemble matted hair. The bright red-pink bodies are intracytoplasmic inclusions (examples indicated by black arrowheads) in astrocytes and indicate intense gliosis (Rosenthal fibers).
These are the characteristic features of pilocytic astrocytoma.

Source: “PilocyticAstrocytoma 20x HE” by Marvin 101, Wikipedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Typical locations of brain tumors**
© AMBOSS

**Mass effect from glioblastoma multiforme (WHO grade IV astrocytoma)**
CT head (without contrast; axial plane) of a 69-year old man with a history of personality changes and left-sided hemiparesis from glioblastoma
The right cerebral hemisphere is diffusely abnormal, with intermixed hypodense (green overlay), isodense, and hyperdense (red overlay) areas. There is mass effect with sulcal effacement and midline shift to the left (dashed line). The frontal and occipital horns (arrowheads) of the right lateral ventricle are effaced.
Yellow overlay: choroid plexus calcification
Blue overlay: falx cerebri calcification

Source: © IMPP

**Glioblastoma multiforme**
Photomicrograph of a cerebral tissue specimen (H&E stain; high magnification)
A high number and density of highly pleomorphic cells with hyperchromatic and irregular nuclei are visible (examples indicated by arrowheads. These cells are aggregated around the periphery of the necrotic zone (green overlay), forming a nuclear pseudopalisading architecture.
These are the characteristic features of glioblastoma multiforme.

Source: “Histopathological image of cerebral glioblastoma. Hematoxylin & esoin stain.” by KGH, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

Oligodendroglioma

Description: : a tumor that arises from oligodendrocytes
Epidemiology
- Median age: 40–50 years
- Relatively rare: ∼ 10% of primary CNS tumors
Clinical features: : the most common location is the cerebral hemisphere (typically the frontal lobe) → seizures, focal neurological deficits, personality changes
Diagnostics
- Imaging: intra-parenchymal tumor with calcifications [39]
  
  CT: hypodense lesion
  
  MRI
  
  T1: hypointense or mixed lesions
  
  T2: hyperintense lesions
- Biopsy [40]
  
  Cells with a clear cytoplasm and round nucleus (fried egg cells)
  
  Chicken-wire pattern of capillary anastomoses
- Molecular testing: assessment of 1p/19q codeletion [41]
Treatment
- Resection
- Adjuvant radiotherapy and chemotherapy
- Common chemotherapeutic regimens
  [42]
  - Procarbazine PLUS lomustine PLUS vincristine
  - Temozolomide monotherapy
Prognosis
- Recurrence rate ∼ 100%
- 5-year survival rate 50–60%

Oligodendroglioma

Ependymoma

Description: a tumor that arises from ependymal cells of the ventricular system
Epidemiology: peak incidence in children and young adults
Associated conditions: neurofibromatosis type II
Clinical features: the 4^th ventricle is the most common location in children → noncommunicating hydrocephalus → features of increased intracranial pressure (e.g., papilledema, headache)
Diagnostics
- Imaging: intra-parenchymal tumor with calcifications and cystic components due to necrosis and/or hemorrhage
- Biopsy
  
  Perivascular pseudorosettes
  
  Rod-shaped bodies (blepharoplasts) near the nucleus
Treatment
- Resection
- Adjuvant radiotherapy
Prognosis
- Depends on the WHO grade, but usually poor
- Overall 5-year survival rate: 65–90% [43][44]

Ependymoma Ependymal pseudorosette

Medulloblastoma

Description: a highly malignant tumor derived from primitive, neuroectodermal tissue [45]
Epidemiology
- Peak incidence: 1^st decade
- Most common malignant pediatric brain tumor (20–25% of all cases)
Associated conditions: Turcot syndrome
Clinical features
[46]
- The most common location is the cerebellum → cerebellar defects (e.g., broad-based gait)
- Most tumors arise within the cerebellar vermis (midline) → truncal ataxia
- Invasion or compression of the 4^th ventricle → noncommunicating hydrocephalus → features of raised intracranial pressure (e.g., papilledema, vomiting, headache)
- Drop metastases to the spinal cord are common → paraplegia
Diagnostics
[47]
- Imaging: intraparenchymal contrast-enhancing mass [48]
  
  CT scan: isodense or hyperdense mass
  
  MRI
  
  T1: hypointense mass
  
  T2: isointense mass
- Biopsy: anaplastic small round blue cells; that surround a central neuropil (Homer-Wright rosettes) [49]
Treatment
[50]
- Resection
- Adjuvant therapy
  
  Children ≥ 3 years: chemotherapy and craniospinal radiotherapy
  
  Children < 3 years: chemotherapy
- Common chemotherapeutic agents: vincristine, cisplatin, cyclophosphamide, lomustine [50]
Prognosis
- 5-year survival rate: 60–80% [51][52]
- Poor prognostic factors
  [53]
  - Inadequate resection
  - Presence of drop metastases
  - ERBB2 mutation

Medulloblastoma Pediatric fourth ventricular tumor Medulloblastoma in a child

**Pediatric fourth ventricular tumor**
MRI Head (T2-weighted; axial view) of a 7-year-old boy
There is a lobulated heterogeneous posterior fossa mass (green overlay) present in the midline of the cerebellum at the level of the fourth ventricle. The fourth ventricle is obscured by the mass and is, therefore, not well seen in this image.
This is a medulloblastoma, the most common malignant pediatric tumor of the central nervous system. Medulloblastomas most commonly involve the cerebellar vermis, the structure that connects the two cerebellar hemispheres. In the pediatric population, other tumors that commonly occur in similar locations include brainstem glioma, ependymoma, choroid plexus papilloma, atypical teratoid/rhabdoid tumor, and astrocytoma. All of these should be considered in this case, although a brainstem glioma would rather be located predominantly within the brainstem rather than the vermis and is, therefore, less likely.
Arrowhead: basilar artery; C: cerebellum

Source: © IMPP

**Medulloblastoma in a child**
Head MRI (T2 weighted image)
Medulloblastoma within the posterior cranial fossa (green border in overlay). The lesion contains cystic areas, particularly on the left side (green overlay).

Source: © IMPP

Craniopharyngioma

Description: a benign dysontogenetic tumor arising from a remnant of the Rathke pouch (ectodermal derivative)
Epidemiology
- Bimodal distribution: 5–14 years; second peak at 50–75 years
- Most common childhood supratentorial tumor
Clinical features:
The
tumor arises in the suprasellar region and can extend into the intrasellar region. [54]

Compression of the pituitary gland due to intrasellar extension → hypopituitarism

Hypogonadotropic hypogonadism

Failure to thrive

Central diabetes insipidus

Compression of the ventromedial hypothalamic nucleus → hyperphagia and obesity

Compression of the infundibular stalk → disconnection hyperprolactinemia

Compression of the optic chiasm → bitemporal hemianopsia

Compression of interventricular foramina and/or aqueduct → obstructive hydrocephalus
Diagnostics
[55]
- Imaging: suprasellar calcified cyst with a lobulated contour
- Biopsy: cholesterol crystals found in a motor oil-like fluid on gross examination
- Consider obtaining diagnostics for hypopituitarism.
Histological variants
- Adamantinomatous
  (common)
  
  Reticular epithelial cells
  
  Frequently associated with calcifications
  
  Cysts and keratin nodules
- Papillary
  
  Metaplastic squamous cells
  
  Calcifications and cysts are rare.
  
  No keratin nodules
Differential diagnoses
- Pituitary adenoma
- Rathke cleft cyst
Treatment
- Resection
- Adjuvant radiotherapy
- Treatment of hypopituitarism
Prognosis: generally good, with a 10-year survival rate of ∼ 90%; however, the recurrence rate is high [56][57][58]

Tumor at the base of the skull Tumor of the skull base Craniopharyngioma Adamantinomatous craniopharyngioma

**Craniopharyngioma**
MRI head (T1 weighted; with contrast; sagittal plane) of a patient with acute visual loss in the right eye
There is an intrasellar and suprasellar mass (green overlay) with both cystic and solid portions. The solid portions show strong contrast enhancement.

Source: “Craniopharyngioma-t1sagkm-005” by Hellerhoff, Wikimedia Commons, licensed under CC BY 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Adamantinomatous craniopharyngioma**
Photomicrograph of a brain tissue sample (HPS stain; intermediate magnification)
Trabeculae and nests of squamous epithelium (examples indicated by yellow overlay) with palisading cells (examples indicated by blue hatched overlay) are visible.
Additionally, there are multiple cysts (examples indicated by yellow hatched overlay), nodules of anuclear ghost cells (examples indicated by blue overlay) containing wet keratin, and calcifications (examples indicated by blue outline) .
This is the typical histological appearance of an adamantinomatous craniopharyngioma.

Source: “Adamantinomatous craniopharyngioma - intermed mag” by Nephron, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

Pineal gland tumor

Description: a tumor that forms in or near the pineal gland and includes pineocytomas, pineoblastomas, and pineal germinomas
Epidemiology
- ♂ > ♀
- < 1% of all CNS tumors in adults
Clinical features
- Compression of dorsal midbrain leads to:
  
  Compression of tectum → vertical gaze palsy (Parinaud syndrome)
  
  Compression of cerebral aqueduct → noncommunicating hydrocephalus
  
  Compression of hypothalamic inhibiting pathways → increased hCG secretion → precocious puberty
Diagnostics: MRI of the brain and biopsy
Histology
- Approx. 70% are germinomas (similar appearance to testicular seminoma)
- Large vacuolated cells with round nuclei (fried egg cells)
- Lymphoid stroma
Treatment
- Resection
- Adjuvant radiochemotherapy

**Pineal germinoma**
Photomicrograph of a pineal tumor biopsy sample (H&E stain; high magnification)
Large tumor cells with abundant pale cytoplasm and pleomorphic nuclei can be seen (examples marked by green overlay). Additionally, the tumor tissue contains numerous intermixed lymphocytes (comparatively small cells with round dark nuclei).
These histopathological findings are consistent with a pineal germinoma, which was confirmed by immunohistochemistry; ovarian dysgerminomas and testicular seminomas have a very similar appearance.

Source: “Figure 2A. in: Synchronized multiple regression of diagnostic radiation-induced rather than spontaneous: disseminated primary intracranial germinoma in a woman: a case report” by Yuichiro Yoneoka, Itaru Tsumanuma, Shinya Jinguji, Manabu Natsumeda & Yukihiko Fujii, Journal of Medical Case Reports, BioMed Central, licensed under CC BY 2.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

Hemangioblastoma

Description: : a benign, highly vascularized neoplasm
Epidemiology
- Rare
- Peak incidence: 20–50 years
Associated conditions: von Hippel-Lindau disease
Clinical features
- The cerebellum is the most common location → cerebellar defects
- Compression of the 4^th ventricle → non-communicating hydrocephalus → features of raised ICP (e.g., papilledema, headache)
- Erythropoietin production by tumor cells → secondary polycythemia
Diagnostics
- MRI; : sharply demarcated intra-parenchymal cystic mass with a non-enhancing wall and an enhancing mural nodule in ∼ 60% of cases [59][60]
  
  T2: hyperintense mass
  
  T1: hypointense or isointense mass
- Biopsy: thin-walled capillary vessels, densely packed together with scarce parenchyma
Treatment
- Resection
- Antiangiogenic therapy (e.g., bevacizumab)
Prognosis: Recurrence risk is < 20% in sporadic cases. [61]

Cerebellar hemangioblastoma Hemangioblastomas of the central nervous system in Von-Hippel-Lindau syndrome Cerebellar hemangioblastoma (WHO grade I)

**Cerebellar hemangioblastoma (WHO grade I)**
Photomicrograph of a cerebellar tissue specimen (HPS stain; high magnification)
Numerous polygonal neoplastic stromal cells with lipid-laden vacuoles (examples indicated by arrowheads) can be seen, resulting in the typical clear-cell appearance. Additionally, there is an abundance of small, thin-walled blood vessels, many of which are densely packed together (examples indicated by blue overlay).

Source: “Cerebellar hemangioblastoma high mag” by Michael Bonert ("Nephron"), Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Hemangioblastoma**
Photomicrograph of a biopsy from a cerebellar mass (H&E stain; high magnification)
Numerous thin-walled small blood vessels (examples indicated by yellow overlay) containing red stained erythrocytes are visible throughout the tumor.
Surrounding the blood vessels large stromal cells (examples indicated by blue overlay) with pale intracytoplasmic lipid inclusions (so-called "foamy" cytoplasm) can be seen.
This appearance is indicative of hemangioblastoma. The diagnosis was confirmed by immunohistochemistry.

Source: “Hemangioblastoma Histology HE” by Marvin 101, Wikimedia Commons, licensed under CC BY-SA 2.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 2.0.

Primary CNS lymphoma (PCNSL)

Definition [9][62]

PCNSL is a rare form of extranodal non-Hodgkin lymphoma that affects the CNS (e.g., brain, eyes, spinal cord, CSF).

Epidemiology [9]

∼ 4% of CNS neoplasms [9]
Highest incidence: adults aged 70–79 years [9]
Commonly associated with immunosuppression (e.g., poorly controlled HIV/AIDS) and/or EBV infection

Clinical features [9]

Focal neurological deficits
Nonspecific cognitive or behavioral changes
Signs of increased ICP, e.g., headache
Seizures (less common)

Diagnostics [9][63]

Initial evaluation

Neuroimaging
- Gadolinium-enhanced MRI brain
  
  Obtain for all patients.
  
  Supportive findings include periventricular lesions with homogeneous enhancement.
- Gadolinium-enhanced MRI spine: Obtain if there are symptoms of spinal cord lesions.
Histopathology or
cytopathology: necessary for diagnostic confirmation
- Preferred: stereotactic brain biopsy
- Alternatives
  
  Lumbar puncture: CSF cytology or flow cytometry
  
  Vitrectomy: vitreous fluid cytology or flow cytometry

When present, lymphoma cells in CSF or vitreous fluid may be sufficient to establish a diagnosis of PCNSL. [9]

Ring-enhancing lesions in the brain

Additional evaluation [63]

Pretreatment evaluation
- Clinical evaluation
  - Thorough physical examination including lymph nodes and testicles
  - Cognitive assessment to establish baseline cognitive function
- Laboratory studies
  - CMP: Ensure hepatic and renal function are adequate for undergoing treatment.
  - LDH: Elevated LDH is a poor prognostic factor.
  - HIV testing
Staging
- Obtain
  NHL staging, including:
  
  Lumbar puncture with CSF assessment
  
  Whole-body imaging
  
  Bone marrow biopsy
- Refer for ophthalmology evaluation (including a slit-lamp examination).
- Assess for secondary malignancies.

Treatment [9][62]

Optimal treatment regimens are an area of ongoing investigation.
Most regimens include rituximab, high-dose methotrexate, and an alkylating agent.
Surgical resection is usually not indicated.
Low-dose whole brain radiotherapy can be used as part of consolidation therapy or palliative therapy.
Monitor for complications of brain tumors.

Glucocorticoids can decrease diagnostic yield in lymphoma. Except in situations of life-threatening increased ICP, avoid glucocorticoid use until diagnostic tissue and fluid samples have been obtained. [9]

Prognosis [9]

Variable
Typically better than other primary CNS tumors but less favorable than non-CNS lymphomas

Primary brain tumors according to age

Pediatric primary brain tumors [64][65][66]

Most
pediatric brain tumors are primary.
- Most common type of benign pediatric primary brain tumor: pilocytic astrocytoma
- Most common malignant pediatric primary brain tumor: medulloblastoma
Brain tumors are the second most common cause of pediatric cancer; after leukemia, accounting for approx. 20% of all cases of pediatric cancer and the primary cause of pediatric cancer deaths in the US.

Overview of pediatric primary brain tumors [47][66][67]
Tumor	Precursor	Typical location [45]	Typical histology [49][68]
Supratentorial
Craniopharyngioma [55]	Rathke pouch (ectoderm)	Suprasellar region	Nests of stratified squamous epithelium with internal areas of lamellar keratin deposits Cholesterol crystals
Infratentorial
Pinealoma	Pineal gland	Dorsal midbrain (compression of tectum, cerebral aqueduct, and hypothalamic inhibiting pathways)	Large vacuolated cells with round nuclei (fried egg cells) Lymphoid stroma Similar to germ cell tumors such as testicular seminoma
Pilocytic astrocytoma	Astrocytes	Posterior cranial fossa	Rosenthal fibers: eosinophilic fibers with corkscrew-like configuration GFAP positive
Medulloblastoma	Primitive, neuroectodermal tissue	Cerebellar vermis	Small, round blue cells Homer-Wright rosette Synaptophysin positive
Ependymoma [69]	Ependymal cells	4^th ventricle	Perivascular pseudorosettes: tumor cells that are arranged in a papillary structure around a central blood vessel

In children, most primary brain tumors arise infratentorial, craniopharyngiomas being an important exception.

Typical locations of brain tumors Cerebellar pilocytic astrocytoma Posterior fossa mass Rosenthal fibers Pediatric fourth ventricular tumor Medulloblastoma in a child Ependymoma Ependymal pseudorosette Tumor at the base of the skull Adamantinomatous craniopharyngioma Pineal germinoma

Adult primary brain tumors [2]

Primary
brain tumors are less common than
brain metastases in adults.

Most common benign primary brain tumor in adults: meningioma

Most common malignant primary brain tumor in adults: glioblastoma multiforme
Primary brain tumors account for 1–2% of cancer cases in adults.

Overview of adult primary brain tumors [47][67]
Tumor	Precursor	Typical locations [45]	Typical histology [49]
Glioblastoma multiforme (WHO grade IV astrocytoma) [70]	Glial cells (e.g., astrocytes)	Cerebral hemispheres (supratentorial) May cross the corpus callosum (butterfly glioma)	Pleomorphic anaplastic cells that form pseudopalisades due to central necrosis or hemorrhage Microvascular proliferation GFAP positive
Meningioma [71]	Arachnoid cap cells	Extra-parenchymal tumor that can occur in supratentorial (often parasagittal) or infratentorial regions	Spindle cells arranged in whorls Psammoma bodies
Hemangioblastoma [72]	Vascular system origin	Cerebellum (infratentorial)	Densely packed thin-walled capillaries
Schwannoma [73]	Schwann cells	Cerebellopontine angle (infratentorial)	Spindle cells in palisades (Antoni A tissue) alternating with myxoid areas (Antoni B tissue) S-100 positive
Oligodendroglioma [41]	Oligodendrocytes	Frontal lobes (supratentorial)	Large vacuolated cells with round nuclei (fried egg cells) Chicken-wire pattern of capillary anastomoses
Pituitary adenoma [74]	Pituitary adenotrophic cells (typically lactotrophs)	Sella turcica (supratentorial)	Monomorphic, acidophilic or basophilic, polygonal cells arranged in sheets or cords

In adults, most primary brain tumors arise supratentorially, hemangioblastomas and schwannomas being important exceptions.

Glioblastoma multiforme (WHO grade IV astrocytoma) Mass effect from glioblastoma multiforme (WHO grade IV astrocytoma) Garland-like enhancement in glioblastoma Glioblastoma in the temporal lobe Bilateral glioblastoma (butterfly glioma) Olfactory groove meningioma Dural based mass Parasagittal meningioma Dural based lesion Dural-based lesion Sphenoid wing meningioma Meningioma with central necrosis Foramen magnum meningioma Cerebellar hemangioblastoma Cerebellar hemangioblastoma (WHO grade I) Vestibularis schwannoma (acoustic neuroma) Acoustic neuroma in a 43-year-old patient Schwannoma (neurilemoma) Oligodendroglioma

**Posterior fossa mass**
MRI head (T1-weighted; with contrast; A: axial view; B: coronal view) of a 19-year-old patient
There is a large mass within the midline of the posterior fossa predominantly located within the pons but also extending towards and indenting the cerebellar peduncles and cerebellar hemispheres. Most of the lesion does not enhance and is cystic, demonstrated by the hypointense signal (green overlay). There is peripheral enhancement, demonstrated by the hyperintense signal, with a particularly prominent region of enhancement shown posteriorly on the axial image (red overlay), representing a mural nodule.
This mass is a pilocytic astrocytoma. The mass is in an atypical region, considering the patient's age, as these tumors usually arise in the posterior fossa in children and in the supratentorial area in adults. Other tumors that occur in a similar location in the posterior fossa would be medulloblastoma, hemangioblastoma, and ependymoma.

Source: “Figure 4. in: Stereotaxic gamma knife surgery in treatment of critically located pilocytic astrocytoma: preliminary result” by Raef FA Hafez, World Journal of Surgical Oncology, BioMed Central, licensed under CC BY 2.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Rosenthal fibers**
Photomicrograph of a tissue section of a brain mass (H&E stain; high magnification)
There is an abundance of eosinophilic, fusiform inclusions (Rosenthal fibers; examples indicated by blue overlay).
Rosenthal fibers are intracellular inclusions within astrocyte cytoplasmic processes. They represent a nonspecific degenerative changes that are often found in CNS tumors (in this case in pilocytic astrocytoma).

Source: “Rosenthal HE 40x.jpg” by Marvin 101, Wikimedia commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Olfactory groove meningioma**
CT head (with contrast; axial plane)
A rounded circumscribed extraaxial mass (blue overlay) located in the midline low anterior cranial fossa shows homogenous contrast enhancement.

Source: © IMPP

**Parasagittal meningioma**
MRI brain (T1-weighted, with contrast, sagittal plane) of a 68-year-old with reduced strength and increasing discomfort in his left leg.
There is a well-defined intracranial mass overlying and appearing adherent to the inner surface of the cranium in the parasagittal region. It enhances intensely and homogeneously. This mass compresses the surrounding brain parenchyma without invading it.
Meningiomas arising from the sagittal midline normally arise from the falx cerebri, the dural fold separating the two cerebral hemispheres, and are given the subtype of parasagittal meningioma.

Source: © IMPP

**Dural based lesion**
MRI head (T1-weighted; with contrast; sagittal plane) of a 58-year-old patient with parosmia.
There is a large, well-defined mass with homogeneous contrast enhancement in the olfactory groove (green overlay.
This is an example of an olfactory groove meningioma.

Source: © IMPP

**Sphenoid wing meningioma**
MRI brain (T1-weighted, with contrast, axial plane)
There is a well-defined intracranial mass (green overlay) overlying the left sphenoid bone demonstrating intense homogeneous enhancement. There is thickening and enhancement of the surrounding dura, and the lesion is also continuous with the dura, known as the dural tail sign (blue overlay). The bone underlying the meningioma is enlarged compared to the contralateral side and demonstrates heterogeneous signal (red overlay), representing hyperostosis. The enlargement of this bone has resulted in mild anterior displacement of the left eye (proptosis; asterisk).
The intense homogeneous enhancement, dural tail sign, and hyperostosis are common features of meningiomas.

Source: “Keilbeinmeningeom MRT T1KMax” by Hellerhoff, Wikimedia Commons, licensed under CC BY 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Meningioma with central necrosis**
CT, axial view, plain (left) and with IV contrast (right)
Large, sharply demarcated, hyperdense lesion with a central hypodense area located in the left parietal region. Homogenous uptake of contrast medium apart from the hypodense central region. Discrete perifocal edema, which indicates compression of the surrounding tissue.

Our great thanks to PD Dr. M. Jergas (Center for Diagnostic and Interventional Radiology, St. Elizabeth Hospital, Cologne) for kindly providing this image.

**Foramen magnum meningioma**
MRI of the neck and base of the skull (left: T1-weighted, with contrast, sagittal plane; right: T2-weighted, sagittal plane)
There is a well-defined mass in the anterior aspect of the foramen magnum, which enhances on the T1-weighted post-contrast image (red overlay) and appears hyperintense to gray matter on the T2-weighted image (green overlay). The mass is continuous with the adjacent thickened and enhancing dura (arrowhead). This is known as the “dural tail sign.”
The dural tail sign suggests lesion originates from the dura mater. The sign is most commonly seen in meningiomas but may also be seen in other malignancies originating in the dura mater, such as lymphoma and metastasis.

Source: “Figure 1, in: Insidious Presentation of a Foramen Magnum Meningioma – A Case Report” by Panagiotis Zogopoulos, Elyns Group, licensed under CC BY 3.0. Modifications: image has been cropped. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Psammoma body and meningocytic whorl**
Photomicrograph of tissue biopsied from a brain tumor (H&E stain)
Several eosinophilic spindle-shaped cells with large nuclei containing prominent nucleoli are visible. The cells are arranged in a whorl-like pattern.
- Meningocytic whorl: the whorl on the right, which is composed of layers or lamellae of cells, resembling the layers of an onion
- Psammoma body: the whorl on the left, which has an acellular basophilic core surrounded by acellular lamellae. Psammoma bodies represent dystrophic calcification in areas of apoptotic tumor cells.
Psammoma bodies and spindle-shaped cells arranged in onion-skin whorls are pathognomonic features of meningioma.

Source: © IMPP

**Vestibularis schwannoma (acoustic neuroma)**
Cranial MRI
Upper left: T2-weighted image (axial view)
Lower left and right: T1-weighted images after application of contrast agent (axial and coronal views)
A tumor is visible on the right side between the brainstem and the cerebellum (green overlay), extending into the porus acousticus (arrow). There is strong contrast enhancement within the lesion and it has a hypointense center (red overlay), suggesting necrosis.

Source: © IMPP

**Acoustic neuroma**
Cranial MRI (T1-weighted; with contrast; axial view)
An intensely contrast-enhancing, homogeneous mass (green overlay) is visible in the right cerebellopontine angle.
This is the typical appearance of an acoustic neuroma.

Source: “Akustikus-Schwannon_rechts_MRT_T1KM_axial_002” by Hellerhoff, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Acoustic neuroma in a 43-year-old patient**
Photomicrograph of a tumor arising from the vestibular portion of cranial nerve VIII (H&E stain; medium magnification)
A characteristic finding of neuromas is the simultaneous occurrence of areas with densely packed nuclei (palisade pattern; A) and scattered or anuclear areas (B). There is also a large number of vacuolated cells (C).

Source: © IMPP

**Schwannoma (neurilemoma)**
Photomicrograph of a biopsy from a peripheral nerve tumor (H&E stain)
Antoni A area (A): area of high cellularity with Verocay bodies. The Verocay bodies consist of rows of pallisading nuclei (green overlay) interspersed with anuclear eosinophilic areas (red overlay).
Antoni B area (B): paucicellular area with unstained myxoid stroma
This is the typical histological appearance of a schwannoma, a benign tumor of the nerve sheath.

Source: “Schwannoma - Antoni A and B - very high mag” by Michael Bonert ("Nephron"), Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

Brain metastases

Definition

Brain metastases are secondary brain tumors due to metastasis of primary malignancies of other organs.

Epidemiology

Most common cause of brain tumors in adults [11]
Rare in children < 14 years of age [75]

Etiology [76]

Lung cancer (most common) [76]
Breast cancer
Pancreatic cancer
Malignant melanoma
Renal cell carcinoma
Colorectal carcinoma
Testicular cancer [77]

Clinical features

Onset: acute or subacute due to rapid tumor growth
Seizures
Focal neurological deficits
Cognitive deficits
Headaches

Diagnostics [2]

Gadolinium-enhanced
MRI
- Well-circumscribed tumors at the junction of gray and white matter and/or watershed areas of the arterial system [78]
- Small metastases: homogeneous enhancement
- Large metastases: ring enhancement due to central necrosis
Further evaluation
- If the primary tumor is unknown: Obtain “Diagnostics of cancer of unknown primary.”
- If no primary tumor is identified: Obtain biopsy of the brain metastasis. [4]

Brain metastases in lung cancer Cerebral metastasis in lung carcinoma 1/2

Treatment [4][79]

Management of brain metastases is based on the primary tumor type, extent of metastases, and the patient's performance status.

Anticancer therapies: typically involves a combination of systemic and local therapy
- Systemic therapy: chemotherapy, cancer immunotherapy, and/or targeted agents
- Local therapy: radiosurgery, radiation therapy, and/or surgical resection
  
  Limited brain metastases: surgical resection or stereotactic radiosurgery (e.g., Gamma Knife, CyberKnife, proton beam)
  
  Extensive brain metastases: stereotactic radiosurgery and/or whole-brain radiotherapy (WBRT)
  
  Tumors causing mass effect: Consider surgical resection.
Supportive care
- Glucocorticoids; (e.g., dexamethasone) as needed to reduce tumor edema and ICP [80]
- Palliative care for patients with a high primary tumor burden and a poor functional status (based on Karnofsky performance status)

Prognosis [81]

Varies widely based on primary tumor and patient factors
The brain metastases prognostic index estimates survival in patients with brain metastases.

**Brain metastases in lung cancer**
CT head (with contrast; axial plane) of a patient with a history of lung cancer presenting with weight loss, gradual reduction in consciousness, and deficits in swallowing, speech, coordination, and gait
Cerebellar (green overlay) and brainstem (red overlay) lesions that show intense contrast enhancement are suspicious for metastases.
P: petrous bone; S: sphenoid bone; T with arrows: tentorium cerebellum

Source: © IMPP

Acute management checklist

Consult neurosurgery and oncology.
Start VTE prophylaxis. [82]
Manage increased intracranial pressure (ICP), if present.
- Urgent neurosurgery and anesthesiology consult
- Assess and secure the airway.
- Consider therapeutic hyperventilation.
- Consider dexamethasone in patients with cerebral edema.
- Consider mannitol
- Admission to ICU and ICP monitoring
Serial neurologic examination
Admission to neurology or oncology service

External Resources

2022 ASCO/SNO/ASTRO Guideline for Treatment of Brain Metastases

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