occur here, enlarged PVSs may cause obstructive

hydrocephalus. Prominent PVSs also occur in the subcortical

and deep white matter. They are pial-lined, interstitial fluidcontaining structures that tend to occur in clusters of variably

sized cysts. Most PVSs suppress completely; 75% are

surrounded by normal-appearing brain, which helps

distinguish them from porencephalic cysts.

Hippocampal sulcus remnant cysts (HSRCs) are common

normal variants, seen as a "string" of small CSF-like cysts lying

in the hippocampus just medial to the temporal horn of the

lateral ventricle. They are caused by defective or incomplete

fusion of the embryonic cornu ammonis and dentate gyrus

and are of no clinical significance.

Porencephalic cysts are the 3rd most common supratentorial

parenchymal cysts. They may communicate with the ventricles

and are typically lined by gliotic white matter, not ependyma,

and are caused by brain destruction (e.g., peri- or antenatal

insult). The brain surrounding a porencephalic cyst is typically

hyperintense on T2WI and FLAIR.

Periventricular cysts of newborns encompasses a wide,

overlapping variety of periventricular cystic lesions that ranges

from cystic periventricular leukomalacia to connatal and

germinolytic cysts.

Neuroglial cysts, sometimes called neuroepithelial cysts, are

benign glial-lined cavities buried within the cerebral white

matter. Although they can occur anywhere, the frontal lobe is

the most common site. They tend to be solitary, whereas PVSs

are usually collections of multiple cysts of different sizes. A

choroid fissure cyst is a neuroglial cyst that occurs anywhere

along the infolded choroid fissure. Most are found medial to

the temporal horn of the lateral ventricle. HSRCs occur when

there is incomplete fusion of the cornu ammonis and the

dentate gyrus. HSRCs are often multiple, appearing like a

string of small CSF-containing cysts along the lateral margin of

the hippocampus.

Supratentorial intraventric

 

using FLAIR and DWI. ACs suppress completely on FLAIR and

do not show diffusion restriction.

Extraaxial tumors, such as meningioma, schwannoma,

pituitary macroadenoma, and craniopharyngioma, may be

associated with prominent extratumoral cysts. These

nonneoplastic TACs occur in both the supra- and infratentorial

compartments.

TACs are benign collections of fluid that vary from clear and

CSF-like to proteinaceous. TACs are typically positioned

between at the tumor-brain interface, between the mass and

adjacent cortex. Whether TACs are true ACs, obstructed PVSs

(Virchow-Robin), or fluid collections mostly lined by gliotic

brain is debatable.

Scalp and skull cysts are less common than intracranial cysts.

Sebaceous cysts [more accurately termed trichilemmal cysts

(TCs)] are a common scalp mass in middle-aged and older

patients. Most are identified incidentally on MR and CT scans.

TCs can be solitary or multiple, are well delineated, and vary in

size from a few millimeters to several centimeters. The classic

finding is a subepidermal scalp tumor in a woman over the age

of 60 years.

Leptomeningeal cysts, also known as "growing fractures," are

a rare but important extraaxial cyst that is most commonly

found in the parietal bone. An enlarging calvarial fracture

adjacent to posttraumatic encephalomalacia is typical. The

vast majority of patients are under 3 years of age. They

present with an enlarging, palpable soft tissue mass. Fluid and

encephalomalacic brain extrude through torn dura and

arachnoid and then through the enlarging linear calvarial

fracture. Leptomeningeal cysts are seen as linear lucent skull

lesions with rounded, scalloped margins.

Infratentorial extraaxial cysts: Most nonneoplastic cysts in

the posterior fossa occur off midline. The 2 major cyst types

found in this location are ECs and ACs.

The cerebellopontine angle (CPA) is by far the most common

posterior fossa sublocation of an EC. Occasionally, an EC

occurs in the 4th ventricle. A 4th ventricular EC can mimic a

trapped, dilated 4th ventricle, but ECs do not suppress on

FLAIR and usually exhibit some degree of restricted diffusion.

The next most common posterior fossa cyst is AC. Although

ACs can also occur in the midline cisterna magna, the CPS is

the most common site. TACs sometimes occur in the CPA

cistern. Most are associated with vestibular schwannoma, but

a CPA meningioma may also cause formation of a TAC.

NEs are congenital endodermal cysts that are much more

commonly found in the spinal canal. Intracranial NE cysts occur

in the cerebromedullary cistern and are usually midline or

slightly off midline, lying just anterior to the pontomedullary

junction. Sometimes NE cysts occur off midline, in the lower

CPA (cerebromedullary) cistern. Bony skull defects can occur

but are rare.

An anatomic variant that can be confused with a posterior

fossa NE cyst is retroclival ecchordosis physaliphora (EP),

found in about 2% of autopsies. EP is a gelatinous notochordal

Cysts, and Disorders

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Primary Nonneoplastic Cysts Overview

remnant that can occur anywhere from the dorsum sellae to

the sacrococcygeal region. Intracranial EPs typically occur in

the prepontine cistern and are attached to a defect in the

dorsal clivus by a thin, stalk-like pedicle. NE cysts and EPs are

both hyperintense on T2WI. Chordomas are the malignant

counterparts of ecchordosis.

Intraaxial Cysts

Supratentorial intraaxial cysts: Here, anatomic sublocation is

key to the differential diagnosis. Parenchymal cysts represent

a completely different group than intraventricular cysts. The

most common parenchymal cysts in the brain are enlarged

PVSs (Virchow-Robin). PVSs have a distinct predilection for the

basal ganglia, where they tend to cluster around the anterior

commissure. The midbrain is another common site. When they

 

156

Primary Nonneoplastic Cysts Overview

General Approach to Brain Cysts

General Considerations

Overview: Cysts are common findings on MR and CT brain

scans. There are many types of intracranial cysts, some

significant, some incidental. In this section, we exclude cystic

neoplasms (such as pilocytic astrocytoma and

hemangioblastoma), solid neoplasms that commonly have

intratumoral cysts (such as ependymoma), and tumors that

often display central necrosis (e.g., glioblastoma).

We also exclude parasitic cysts (neurocysticercosis, hydatid

disease) and cystic brain malformations (Dandy-Walker

spectrum) from the discussion. Thus, the focus of this

particular section is primary nonneoplastic cysts.

Because the etiology, pathology, and clinical importance of

nonneoplastic cysts is so varied, classifying them presents a

real challenge. Some neuropathologists typically classify cysts

according to the histology of the cyst wall. Others group them

according to putative origin or pathogenesis.

In a schema based on pathogenesis, cysts may occur as normal

anatomic variants [e.g., enlarged perivascular (Virchow-Robin)

spaces] (PVSs), congenital inclusion cysts [e.g., dermoid and

epidermoid cysts (ECs)], or lesions derived from embryonic

ecto-/endoderm [colloid cysts (CCs) and neurenteric cysts

(NCs)]. Of course, there is a group of miscellaneous cysts [such

as choroid plexus cysts (CPCs) and nonneoplastic tumorassociated cysts (TACs)] that does not fit nicely into any

category.

Neurologists and their neuroradiology colleagues face a very

real dilemma: A cystic-appearing lesion is identified on MR or

CT. What is it? What else could it be? Histopathology of the

cyst wall isn't a practical consideration. What is readily

apparent is (1) the anatomic location of the cyst, (2) its

imaging characteristics (density/signal intensity, presence or

absence of calcification, enhancement, etc.), and (3) the

patient's age. The recommended initial approach to analyzing

brain cysts is anatomy based.

Anatomy-Based Approach to Brain Cysts

General Considerations

Key features: Four features help the diagnostic approach to

cystic-appearing intracranial lesions. The 1st step is to

determine whether the cyst is intra- or extraaxial. If it is

extraaxial, is the cyst supra- or infratentorial? Is it midline or off

midline? If a cyst is intraaxial, is it supra- or infratentorial? Is it

parenchymal or intraventricular? Although many intracranial

cysts certainly may occur in > 1 location, some sites are

"preferred" by certain cysts.

Extraaxial Cysts

Supratentorial extraaxial cysts: Nonneoplastic, noninfectious

extraaxial cysts can occur in the midline or off midline. Pineal

and Rathke cleft cysts occur only in the midline. Although

dermoid cysts seem to prefer a midline location like the

suprasellar cistern, they also occur off midline. Look for

rupture with fatty "droplets" in the subarachnoid cisterns.

Arachnoid cysts (AC) are usually off midline. In the

supratentorial compartment, midline ACs are relatively rare.

The most frequent midline locations are the suprasellar

cistern, followed by the quadrigeminal cistern and velum

interpositum. Large suprasellar ACs usually present in children

and may cause obstructive hydrocephalus.

The most common off midline extraaxial supratentorial cyst is

an AC. Although these can occur virtually anywhere, the

middle cranial fossa is the location of at least 50% of all ACs.

Occasionally, ACs occur over the cerebral convexities, most

commonly over the parietal lobe. ACs follow cerebrospinal

fluid (CSF) on all sequences and are differentiated from ECs

 https://mawadealmaousoaa.blogspot.com/search?q=Imaging+in+Neurology

Pseudoresponse

KEY FACTS

TERMINOLOGY

• Antiangiogenic agents may substantially reduce contrast

enhancement in glioblastoma multiforme related to

reduced vascular permeability rather than actual tumor

response

○ Bevacizumab (Avastin): Anti-VEGF is main antiangiogenic

agent currently used for treatment of recurrent

malignant gliomas

○ Cediranib: VEGF receptor tyrosine kinase inhibitor has

been tested in recent high-grade glioma treatment trials

IMAGING

• Decreased enhancement in patient with malignant glioma

treated with anti-VEGF agent

○ May see persistent FLAIR and diffusion restriction,

despite decreased enhancement

• DWI and ADC have been proposed as imaging markers for

tumor response in presence of antiangiogenic agents to

address pseudoresponse

• Beware, decreased enhancement in tumor follow-up study

may be true treatment response or pseudoresponse in

setting of newer therapies

• DSC: Early changes in relative cerebral blood volume after

initiation of antiangiogenic therapy may distinguish

pseudoresponse from true treatment response

TOP DIFFERENTIAL DIAGNOSES

• Treatment response

• Steroid effect

CLINICAL ISSUES

• Antiangiogenic agents normalize hyperpermeable tumor

vasculature and restore blood-brain barrier

• Local response to tumor growth is controlled, but diffuse

infiltration and distant metastases are common

• Antiangiogenic agents significantly improve 6-month

progression-free survival but may not affect overall survival

(Left) Axial T1 C+ MR in a GBM

patient who progressed on

standard therapy with

radiation and Temodar shows

there is a heterogeneously

enhancing mass involving the

genu of the corpus callosum

﬇. Avastin therapy was

started immediately after this

MR examination. (Right) Axial

T1 C+ MR in the same patient

4 weeks after the start of

Avastin shows a marked

decrease in the enhancing

mass involving the genu of the

corpus callosum ﬇. The FLAIR

and DWI showed stable

hyperintensity and mass

effect.

(Left) Axial T1 C+ MR in the

same patient 8 weeks later

shows an increase in the size

of the corpus callosum

enhancing mass ﬇. (Right)

Axial FLAIR MR in the same

patient shows a marked

increase in the size ﬇ and

associated mass effect of the

corpus callosum mass related

to progressive tumor.

Decreased enhancement on

the prior MR is a result of

pseudoresponse from the

antiangiogenic therapy, rather

than true tumor response.

Diffuse tumor infiltration is

common after antiangiogenic

therapy.

Brain: Pathology-Based Diagnoses: Neoplasms,

Cysts, and Disorders

 

Pseudoprogression (PsP)

KEY FACTS

TERMINOLOGY

• Treatment-related increase in contrast enhancement

mimics tumor progression

• Classically described after treatment with chemoradiation

(temozolomide with radiation therapy)

• Typically occurs within 3-6 months after conclusion of

radiation therapy (XRT)

IMAGING

• New enhancing lesion + ↑ FLAIR hyperintensity in treated

malignant glioma at 3-4 months after XRT completion

• T2/FLAIR: Increased hyperintensity with mass effect

• DWI: Higher ADC values in PsP compared with tumor

• DSC MR

○ Lower mean rCBV values in PsP compared with tumor

• DCE MR

○ Mean K trans (volume transfer constant) is lower in PsP

compared with true progression

• MRS: No significant elevation of choline in PsP

• Best imaging: Contrast-enhanced MR, DWI, ± MRS, MRP

• Follow-up studies may be necessary to make accurate

diagnosis of PsP

• Knowing clinical history and timing of therapy is key to

accurate brain tumor imaging

TOP DIFFERENTIAL DIAGNOSES

• Recurrent malignant glioma

• Radiation necrosis

CLINICAL ISSUES

• Current standard of care for malignant gliomas is surgical

resection followed by concurrent XRT and chemotherapy

with temozolomide (Temodar)

○ PsP occurs in ~ 35-50% of patients

• PsP is self-limited, enhancing lesions resolve without new

treatment

• PsP has been associated with improved survival

• Important to recognize that not all new enhancement in

patient with treated glioblastoma is progressive tumor

(Left) Axial T1 C+ MR in a 48-

year-old man treated with

radiation therapy and

Temodar for 3 months for his

malignant glioma shows new

enhancement ﬊ in the frontal

lobes bilaterally. His initial

postoperative MR study

showed no enhancement. He

was clinically doing well.

(Right) Axial T1 C+ MR in the

same patient 4 weeks later

shows a marked decrease in

the enhancement ﬊ without

a change in therapy. Imaging

findings are related to

pseudoprogression, not true

progression, likely related to

an inflammatory response.

(Left) Axial T1 C+ MR in a 62-

year-old woman with a

multifocal glioblastoma

treated with Temodar and

radiation therapy shows new

enhancement ﬊ in the

hemispheres on her 4-month

scan, concerning for

progressive tumor. (Right)

Axial T1 C+ MR in the same

patient 8 weeks later with no

therapy change shows a

marked decrease in the

enhancing lesions ﬊. The new

enhancement was related to

pseudoprogression, which is

associated with an increased

survival.

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Radiation and Chemotherapy

KEY FACTS

TERMINOLOGY

• Radiation-induced injury may be divided into acute,

subacute/early delayed, late injury

IMAGING

• Radiation injury: Mild vasogenic edema to necrosis

• Radiation necrosis: Irregular enhancing lesion(s)

○ MRS: Markedly ↓ metabolites (NAA, Cho, Cr), ±

lactate/lipid peaks

○ Perfusion MR: ↓ relative cerebral blood volume

compared with tumor

• Leukoencephalopathy: T2 white matter (WM)

hyperintensity, spares subcortical U fibers

• Mineralizing microangiopathy: Basal ganglia, subcortical

WM Ca++, atrophy

• Necrotizing leukoencephalopathy: WM necrosis

• PRES: Posterior circulation subcortical WM edema

• MRS, MR perfusion, PET, or SPECT may help delineate

recurrent tumor from radiation necrosis

TOP DIFFERENTIAL DIAGNOSES

• Neoplasm

• Abscess

• Multiple sclerosis

• Vascular dementia

• Progressive multifocal leukoencephalopathy

PATHOLOGY

• 2nd neoplasms: Meningiomas (70%), gliomas (20%),

sarcomas (10%)

○ More aggressive tumors, highly refractory

○ Incidence: 3-12%

• Radiation-induced vascular malformations: Capillary

telangiectasias ± cavernomas

CLINICAL ISSUES

• Overall incidence of radionecrosis: 3-9%

• Worse prognosis: Younger patient at treatment

(Left) Axial NECT shows

extensive calcification in the

subcortical white matter (WM)

﬉ in a 20-year-old patient.

Mineralizing microangiopathy

usually results after a

combination of radiation

therapy and chemotherapy 2

or more years after treatment.

(Right) Axial SWI in an adult

patient with

neurofibromatosis and optic

nerve glioma status post

radiation therapy in childhood

shows innumerable

"blooming" hypointense foci

﬈ consistent with radiationinduced vascular

malformations.

(Left) Axial FLAIR MR in a 22

year old with acute leukemia

treated with intrathecal

methotrexate shows confluent

periventricular and deep WM

hyperintensities ﬉ with

sparing of the subcortical WM.

(Right) Axial T1 C+ MR in the

same patient shows multiple

nodular enhancing lesions in

the WM ﬈. Findings are

consistent with

chemotherapy-induced

necrotizing

leukoencephalopathy.

Leukoencephalopathy is a

potentially serious

complication of

chemotherapy.

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154

 

Paraneoplastic Syndromes and Limbic Encephalitis

KEY FACTS

TERMINOLOGY

• Remote neurological effects of cancer, associated with

extra-CNS tumors

○ Most common tumor: Small cell lung carcinoma

• Limbic encephalitis (LE) is most common clinical

paraneoplastic syndrome

IMAGING

• Limbic encephalitis: Hyperintensity in mesial temporal

lobes, limbic system

○ Mimics herpes encephalitis but subacute/chronic

• Paraneoplastic cerebellar degeneration (PCD): Cerebellar

atrophy

• Brainstem encephalitis: T2 hyperintensity in midbrain, pons,

cerebellar peduncles, basal ganglia

• Most paraneoplastic syndromes do not have associated

imaging findings

TOP DIFFERENTIAL DIAGNOSES

• Herpes encephalitis

• Low-grade (grade II) diffuse astrocytoma

• Status epilepticus

• Gliomatosis cerebri

CLINICAL ISSUES

• < 1% of patients with systemic cancers develop

paraneoplastic syndrome

• Immune mediated by autoantibodies or cytotoxic T cellrelated mechanisms

○ 60% have circulating serum autoantibodies

• LE: Memory loss, cognitive dysfunction, dementia,

psychological features, seizures

• PCD: Ataxia, incoordination, dysarthria, nystagmus

• Brainstem encephalitis: Brainstem dysfunction including

cranial nerve palsies, visual changes

• Treatment of primary tumor may improve symptoms

(Left) Axial FLAIR MR shows

abnormal hyperintensity in the

bilateral medial temporal

lobes ﬈, characteristic of

limbic encephalitis, the most

common paraneoplastic

syndrome. Bilateral

involvement is typical of limbic

encephalitis. (Right) Axial

T1WI C+ MR in the same

patient shows no significant

enhancement in the medial

temporal lobes. Enhancement

is often present in limbic

encephalitis. The patient's

symptoms often improve after

treatment of the primary

tumor.

(Left) Axial FLAIR MR in an

older adult with small cell lung

cancer and subacute dementia

shows striking hyperintensity

in the right insula ﬇. (Right)

Coronal T2WI in the same

patient shows abnormal

hyperintensity in both medial

temporal lobes ſt and right

insular cortex ﬇. Imaging of

limbic encephalitis mimics that

of herpes encephalitis;

however, patients with limbic

encephalitis have a subacute

presentation. Hemorrhage

suggests herpes rather than

limbic encephalitis.

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Metastatic Intracranial Lymphoma

KEY FACTS

TERMINOLOGY

• Secondary CNS involvement in patients with systemic

lymphoma (SCNSL)

IMAGING

• Secondary CNS lymphoma: Skull, dura, leptomeninges > >

parenchymal mass

• Best diagnostic clue: Diffusely enhancing dural mass ± bone

involvement

○ May see leptomeningeal enhancement or nonsupression

of cerebrospinal fluid on FLAIR; CT hyperdensity

• Lower relative cerebral blood volume than other tumors

TOP DIFFERENTIAL DIAGNOSES

• Meningioma

• Meningeal metastases

• Primary CNS lymphoma

• "Tumefactive" demyelinating disease (MS, ADEM)

CLINICAL ISSUES

• Prognostic markers suggestive of CNS relapse

○ Elevated serum lactate dehydrogenase levels

○ Presence of B symptoms

○ Extranodal involvement at > 1 site

○ Advanced stage

• Aggressive histologic features increase risk for SCNSL

• Involvement of liver, bladder, testis, or adrenals also

increases risk of CNS spread

• CNS involvement of lymphoma almost always fatal

• Prophylactic CNS chemotherapy recommended for

patients considered at high risk of CNS recurrence

DIAGNOSTIC CHECKLIST

• Occult lymphoma found in 8% of patients presenting with

CNS lymphoma

• SCNSL commonly mimics meningioma or other metastatic

disease

(Left) Axial CECT shows

extensive dural enhancement

﬇ related to metastatic

intracranial lymphoma.

Secondary lymphoma has a

propensity for the meninges.

About 1/3 of systemic

lymphoma patients develop

CNS disease. (Right) Axial T1

C+ MR shows an enhancing

central skull base mass ﬈

with associated dural ﬇ and

leptomeningeal enhancement

ſt within the internal

auditory canals. The clivus is

often involved by metastatic

disease, particularly breast

cancer and lymphoma.

(Left) Axial T1 C+ MR in a 54-

year-old man with systemic

lymphoma shows multiple

enhancing masses. Some

lesions involve the dura ﬇,

whereas others are

parenchymal ſt. Metastatic

intracranial lymphoma often

involves the dura and may

mimic a meningioma. (Right)

Axial T1WI C+ FS MR shows

enhancement along the

maxillary division (V2) of CN5

ſt, extending from the

cavernous sinus into the

pterygopalatine fossa ﬇, in

this patient with systemic

lymphoma and new facial

paresthesias.

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152

 

Miscellaneous Intracranial Metastases

KEY FACTS

TERMINOLOGY

• Brain metastases in locations other than skull/meninges or

parenchyma

IMAGING

• General features

○ > 95% of brain metastases parenchymal

○ Only 1-2% in ventricles, pituitary gland, etc.

○ Sites generally very vascular

○ Extraventricular metastases more diffuse, infiltrative

than parenchymal metastases (usually round)

• Location

○ Choroid plexus ± ventricular ependyma

○ Pituitary gland infundibulum

○ Eye (choroid)

○ Cranial nerves

○ Pineal gland

○ Preexisting neoplasm ("collision tumor")

• Best imaging tool: MR with T1WI C+ FS

○ Metastases almost always enhance

TOP DIFFERENTIAL DIAGNOSES

• Varies with location

• Choroid plexus, ventricle = meningioma

• Pituitary gland, infundibular stalk

○ Pituitary macroadenoma

○ Lymphocytic hypophysitis

○ Lymphoma

• Cranial nerves = neurofibromatosis type 2, lymphoma

• Eye (globe)

○ Ocular melanoma

○ Retinal or choroidal detachment

○ Choroidal hemangioma

DIAGNOSTIC CHECKLIST

• Look for "secret sites" outside parenchyma when imaging

brain for possible metastatic disease

(Left) Submentovertex graphic

shows the typical sites for

miscellaneous

nonparenchymal CNS

metastases. These include the

choroid plexus and ventricles

﬈, pituitary gland,

infundibular stalk ﬊, and eye

(choroid of the retina) st.

(Right) Coronal T1WI C+ MR in

an elderly woman with known

breast carcinoma shows a

thickened, enhancing

infundibular stalk ſt. This was

the only intracranial

metastasis identified in this

patient.

(Left) Axial T1 C+ FS in a

patient with diplopia and

known esophageal cancer

shows an enhancing nodule on

the left 3rd cranial nerve ſt,

as well as on the left optic

nerve/sheath ﬇. Cranial

nerve metastases from

extracranial tumors are less

common than from

hematopoietic neoplasms

(e.g., lymphoma). (Right) Axial

T1 C+ FS in a patient with

systemic B-cell lymphoma

shows multiple metastases to

the choroid plexus ſt. Subtle

ependymal metastases ﬇ are

present along with diffuse

dura-arachnoid thickening.

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