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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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.

Cysts, and Disorders

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Parenchymal Metastases

KEY FACTS

TERMINOLOGY

• Secondary brain tumors (metastases) arise from

○ Tumors outside CNS spreading to CNS (usually via

hematogenous dissemination)

○ Primary CNS neoplasms spreading from 1 site to another

(usually geographic extension, e.g., along WM tracts)

IMAGING

• General features

○ Round enhancing lesion(s) at gray-white interface

(arterial border zones)

○ Most metastases are circumscribed/discrete > >

infiltrating, spherical > > linear

○ 50% are solitary; 20% have 2 metastases

○ 30% of patients have 3 or more

• MR signal intensity varies with

○ Cellularity, nuclear:cytoplasmic ratio

○ Presence/absence of hemorrhage

• Usually no restriction on DWI

○ Exception: Densely cellular metastases may restrict

TOP DIFFERENTIAL DIAGNOSES

• Abscess (solitary or multiple)

• Glioblastoma multiforme

• Cerebral infarction (multiple embolic)

• Demyelinating disease (e.g., tumefactive MS)

PATHOLOGY

• Metastases represent at least 50% of all brain tumors

• In 10% of cases, brain is only site

CLINICAL ISSUES

• Progressive increase in size and numbers is typical

• Median survival with whole-brain XRT = 3-6 months

• Stereotactic radiosurgery alone > whole-brain XRT

• Survival advantage, if 1-4 metastases, avoids deleterious

effects of whole-brain XRT on quality of life, cognition

• Resection of solitary metastasis may improve survival

(Left) Axial graphic shows

parenchymal metastases ﬈

with surrounding edema ﬊.

The gray-white matter

junction is the most common

location. Most metastases are

round, not diffusely

infiltrating. (Right) Close-up

view of an axial section

through an autopsied brain

shows a classic metastasis ﬈

in the classic location, the

gray-white matter junction.

Note the round shape, central

necrosis, and relative lack of

edema. Diffuse

leptomeningeal metastatic

spread ﬇ is also present.

(Left) Axial T2WI MR in a 52-

year-old man with a seizure,

history of melanoma, shows

multiple lesions ſt at the

gray-white matter interfaces.

Moderate edema surrounds

the lesions. One of the lesions

has a hypointense nodule ﬇,

suggesting that at least 1 is a

hemorrhagic metastasis.

(Right) T1 C+ FS MR (same

case) shows that the lesions

enhance ſt. Note small

metastasis st in the right

ventricle choroid plexus that

was not appreciated on T2WI.

The extensive occipital edema

is also from a metastasis (not

seen on this image).

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Leukemia

KEY FACTS

TERMINOLOGY

• Extramedullary leukemic tumors

• Synonyms: Granulocytic sarcoma, chloroma

IMAGING

• Best diagnostic clue: Homogeneous enhancing tumor(s) in

patients with known or suspected myeloproliferative

disorder

• Meningeal (dural-based or pial) > intraparenchymal lesions

• NECT: Hyperdense

• CECT: Moderate uniform enhancement

• MR

○ T2/FLAIR iso- to hypointense

○ Restricted diffusion on DWI

TOP DIFFERENTIAL DIAGNOSES

• Metastatic neuroblastoma

• Meningioma

• Extraaxial hematoma

• Extramedullary hematopoiesis

• Langerhans cell histiocytosis

PATHOLOGY

• CNS leukemia presents in 3 forms

○ Meningeal disease (usually with acute lymphoblastic

leukemia)

○ Intravascular aggregates (leukostasis): Can rupture,

hemorrhage with markedly ↑ leukocyte counts

○ Tumor masses (chloroma)

• Multiple other intracranial manifestations, complications of

leukemia/treatment

○ Posterior reversible encephalopathy syndrome (PRES)

○ Posttransplant lymphoproliferative disease after bone

marrow transplantation

○ Invasive fungal infection

○ Venous thrombosis associated with chemotherapy

○ Late development of cavernous angiomas after radiation

therapy

(Left) Coronal graphic shows

multiple foci of leukemic

infiltrates in the skull

base/paranasal sinuses ſt,

hypothalamus/infundibulum

﬊, basal ganglia ﬉, and dura

﬇. Green color observed at

pathology results in the name

"chloroma." The accepted

term is "granulocytic

sarcoma." (Right) Axial NECT

scan in a child with acute

myelogenous leukemia (AML)

and a palpable scalp mass

shows a hyperdense intra- ﬇

and extracranial mass ſt that

centers on the calvaria.

(Left) Axial T2WI in a child

with AML demonstrates a

hypointense parietal mass ſt

surrounded by a collar of

edema st. AML with

parenchymal metastasis

(cerebral granulocytic

sarcoma) is rare. (Right) NECT

scan in a 5-year-old girl with

AML shows chloroma

infiltrating both trigeminal

nerves, enlarging the cisternal

﬈ and Meckel cave segments

﬊. (Courtesy N. Aggarwal,

MD.)

Cysts, and Disorders

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Intravascular (Angiocentric) Lymphoma

KEY FACTS

TERMINOLOGY

• Rare malignancy characterized by intravascular proliferation

of lymphoid cells with predilection for CNS and skin

IMAGING

• T2/FLAIR multifocal hyperintensities in deep white matter,

cortex, and basal ganglia

○ May mimic infarct

• Diffusion restriction common

• GRE/SWI: Multifocal hemorrhage often seen

• Linear and punctate enhancement typical

○ May see meningeal &/or dural enhancement

• Often mimics vasculitis

TOP DIFFERENTIAL DIAGNOSES

• Vasculitis

• Multi-infarct dementia

• Primary CNS lymphoma

• Neurosarcoid

PATHOLOGY

• Malignant lymphoid cells occlude and distend small

arteries, veins, and capillaries

CLINICAL ISSUES

• Dementia is most common presenting feature

• May present with multiple stroke-like episodes

• Presents in 5th-7th decades; mean: 60-65 years

• Diagnosis may be made by skin or brain biopsy

• Rapidly progressive disease with high mortality rate

○ Mean survival: 7-13 months

• Rare, but underdiagnosed

○ CNS involved in up to 75% of cases

DIAGNOSTIC CHECKLIST

• Imaging of intravascular lymphoma (IVL) is nonspecific, but

IVL should be considered in patients with dementia,

multifocal lesions, and enhancement

(Left) Malignant lymphoid

cells occlude and distend small

arteries ﬉, veins, and

capillaries, resulting in

ischemic lesions ﬊ and

microbleeds ﬈. Meningeal

involvement ﬈ is typical of

intravascular lymphoma (IVL).

(Right) Sagittal T1 C+ MR in a

61-year-old man with known

systemic diffuse large B-cell

lymphoma and a 1-month

history of lethargy and altered

mental status shows diffuse

linear enhancing foci

throughout the basal ganglia

ſt, hemispheric white matter

﬇, and cerebellum st.

(Left) Axial T1 C+ MR in the

same case shows intense,

nearly symmetric

enhancement in the inferior

basal ganglia ſt. Note

numerous punctate enhancing

foci in the putamina st and

thalami ﬇. (Right) Coronal T1

C+ MR in the same case shows

curvilinear enhancement st

following the course of the

penetrating lenticulostriate

arteries. Intravascular

(angiocentric) lymphoma was

found at autopsy.

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Hemangioblastoma

KEY FACTS

TERMINOLOGY

• Hemangioblastoma (HGBL): Highly vascular tumor of adults

most commonly found in posterior fossa (PF), spinal cord

○ 25-40% of HGBLs in von Hippel-Lindau disease (VHL)

IMAGING

• Best diagnostic clue: Adult with cerebellar mass with cyst

and enhancing mural nodule

• General features

○ 50-60% cyst + "mural" nodule; 40% solid enhancing mass

○ 90-95% in posterior fossa

○ 5-10% supratentorial (around optic pathways,

hemispheres; usually in VHL)

TOP DIFFERENTIAL DIAGNOSES

• Metastasis (most common posterior fossa parenchymal

mass in adults)

• Pilocytic astrocytoma (most common neoplasm with cyst +

nodule in child)

• Cavernous malformation

• Hereditary hemorrhagic telangiectasia

PATHOLOGY

• WHO grade I

• Red or yellowish, well-circumscribed, unencapsulated,

highly vascular mass that abuts leptomeninges

• Histology shows stromal cells, innumerable small vessels

CLINICAL ISSUES

• Headache is most common presenting symptom

• Primary therapy = surgical resection

• Begin MR screening of patients from VHL families after 10

years of age

DIAGNOSTIC CHECKLIST

• Most common posterior fossa intraaxial mass in middleaged/older adult is metastasis, not HGBL

(Left) Coronal graphic shows a

classic cerebellar

hemangioblastoma as largely

cystic mass ﬈ with a vascular

tumor nodule ﬇ that abuts

the pial surface. These lowgrade tumors are the most

common primary posterior

fossa tumor in adults. (Right)

Coronal T1 C+ MR shows a

large cyst and mural nodule

ſt in a VHL patient with

multiple hemangioblastomas.

Note the lack of enhancement

﬈ of the cyst wall, which

consists of compressed but

normal cerebellum. The other

hemangioblastomas ﬇ have a

solid enhancing appearance.

(Left) Coronal T2 MR in a 60-

year-old woman with

headaches shows a

heterogeneous cerebellar

mass ſt with prominent flow

voids ﬊ and surrounding

edema. (Right) Coronal T1 C+

MR in the same patient shows

marked enhancement of the

mass ﬇ and a prominent

adjacent vessel ſt.

Hemangioblastoma was found

at surgical resection. The main

imaging differential diagnosis

in this adult was metastatic

disease. These WHO grade I

tumors have an excellent

prognosis in sporadic cases.

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Primary CNS Lymphoma

KEY FACTS

TERMINOLOGY

• Malignant primary CNS neoplasm primarily composed of B

lymphocytes (PCNSL)

IMAGING

• Best diagnostic clue: Enhancing lesion(s) within basal

ganglia &/or periventricular white matter

• 60-80% supratentorial

○ Often involve, cross corpus callosum

○ Frequently contact, extend along ependymal surfaces

• Classically hyperdense on CT (helpful for diagnosis)

• Diffusely enhancing periventricular mass in

immunocompetent patients

• May see hemorrhage or necrosis in immunocompromised

patients

• DWI: Low ADC values

• PWI: Low relative cerebral blood volume ratios

• Periventricular location and subependymal involvement is

characteristic of PCNSL

• Corpus callosum involvement may be seen with PCNSL,

glioblastoma (GBM), and rarely metastases or

demyelination

TOP DIFFERENTIAL DIAGNOSES

• Acquired toxoplasmosis

• GBM

• Abscess

• Progressive multifocal leukoencephalopathy

PATHOLOGY

• 98% diffuse large B-cell, non-Hodgkin lymphoma

CLINICAL ISSUES

• Imaging and prognosis vary with immune status

• 6.6% of primary brain tumors, incidence rising

• Poor prognosis

• Stereotactic biopsy, followed by chemotherapy, ± XRT

(Left) Axial graphic shows

multiple periventricular

lesions with involvement of

the basal ganglia, thalamus,

and corpus callosum, typical of

primary CNS lymphoma

(PCNSL). Note the extensive

subependymal spread of the

disease ﬈. PCNSL typically

extends along ependymal

surfaces. (Right) Axial T1 C+

MR in a 63 year old shows the

classic appearance of PCNSL.

Note the multiple

homogeneously enhancing

masses in the basal ganglia

along the ependymal lining of

the ventricular system ﬈.

(Left) Axial T1 C+ MR shows a

homogeneously enhancing

mass crossing the corpus

callosum splenium ﬊ typical

of PCNSL in this 76-year-old

man with a headache. The

main differential

consideration would be a

glioblastoma, which typically

has a more heterogeneous

appearance. (Right) Axial

T1WI C+ MR in an AIDS patient

shows a ring-enhancing mass

with a target sign ﬈,

suggestive of toxoplasmosis.

Hemorrhage, necrosis, and

ring-enhancing lesions are

typical of PCNSL in AIDS

patients.

Cysts, and Disorders

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Germinoma

KEY FACTS

TERMINOLOGY

• Intracranial germ cell tumor (iGCT)

• iGCTs are intracranial homologue of gonadal germinomas

(ovarian dysgerminoma, testicular seminoma)

IMAGING

• Most common: In/near midline (80-90%)

○ Pineal region ~ 50-65%

○ Suprasellar ~ 25-35%

• Less common: Basal ganglia/thalami ~ 5-10%

• 20% multiple

○ Most common = pineal with suprasellar

• Pineal germinoma

○ Hyperdense pineal region mass engulfs pineal Ca++

○ Strong, often heterogeneous enhancement

○ T2/FLAIR hyperintensity in surrounding brain =

inflammation/granulomatous change

• Suprasellar germinoma

○ Absent posterior pituitary "bright spot"

○ "Fat" stalk/pituitary gland

○ Strong, relatively uniform enhancement

○ May have cysts, hemorrhage (rare)

• Basal ganglia germinoma

○ Rare; hemorrhage common

TOP DIFFERENTIAL DIAGNOSES

• Pineal germinoma

○ Pineocytoma, other pineal GCTs

• Suprasellar germinoma ("fat" infundibulum)

○ Adult = neurosarcoid, metastases

○ Child = Langerhans cell histiocytosis (LCH)

CLINICAL ISSUES

• 90% of patients < 20 years old

○ Pineal region germinoma: M:F ~ 10:1

○ Causes dorsal midbrain syndrome

DIAGNOSTIC CHECKLIST

• Child with diabetes insipidus? Think germinoma or LCH!

(Left) Sagittal graphic shows

synchronous germinomas in

the suprasellar and pineal

regions. Note the

cerebrospinal fluid spread of

tumor in the lateral, 3rd, and

4th ventricles ﬈. (Right) Axial

NECT scan shows typical

findings of pineal germinoma

with a well-demarcated

slightly hyperdense mass ſt

engulfing the calcified pineal

gland ﬇.

(Left) Axial T2WI in a 14-yearold boy with visual symptoms

shows a suprasellar mass ﬈

that is slightly hypointense

relative to gray matter. A 2nd,

smaller mass ﬉ is present in

the pineal gland. (Right) T1 C+

MR in the same patient shows

that the lobulated suprasellar

mass ﬈ enhances strongly.

The pineal mass ﬉ also

enhances uniformly. The

combination of suprasellar

and pineal mass (sometimes

called "double midline"

germinoma) occurs in ~ 20%

of cases.

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Medulloblastoma

KEY FACTS

TERMINOLOGY

• Medulloblastoma (MB)

○ Malignant, invasive, highly cellular embryonal tumor

• 4 distinct MB molecular subgroups

○ Wingless (WNT)

○ Sonic hedgehog (SHH)

○ Group 3

○ Group 4

IMAGING

• MB subgroups arise in different locations

○ Midline (4th ventricle)

– Predominately (but not exclusively) groups 3 and 4

○ Cerebellar peduncle/CPA cistern: WNT

○ Cerebellar hemispheres (lateral): SHH

• NECT: 90% hyperdense (Ca++, hemorrhage uncommon)

• MR: > 90% enhance (group 4 minimal/no enhancement)

○ Restricted diffusion, low ADC

○ T1 C+ essential to detect CSF dissemination

TOP DIFFERENTIAL DIAGNOSES

• Atypical teratoid/rhabdoid tumor

• Ependymoma

• Cerebellar pilocytic astrocytoma

PATHOLOGY

• WHO grade IV (overstates risk of WNT MB)

• Microscopy

○ "Small round blue cell" tumor

○ Neuroblastic (Homer Wright) rosettes (40%)

• Most common histologic type = classic MB

• Less common subtypes: Desmoplastic, MB with extensive

nodularity, large cell/anaplastic

CLINICAL ISSUES

• Most common malignant pediatric brain tumor

• Prognosis varies with subgroup, mutations

○ WNT best, group 3 worst

(Left) Axial graphic shows a

spherical tumor centered in

the 4th ventricle ﬊, typical of

classic medulloblastoma (MB).

Cerebrospinal fluid (CSF)

dissemination ("sugar icing") is

common at initial diagnosis

and is shown in blue ﬈.

(Right) Axial T1WI shows

imaging findings of classic MB,

with a rounded, slightly

hypointense mass ﬈ in the

4th ventricle.

(Left) Axial T1 C+ FS in the

same case shows the mass

mass ﬇ enhances strongly,

somewhat heterogeneously.

No CSF spread is identified.

(Right) DWI in the same case

shows strongly restricted

diffusivity ﬇. Surgery

disclosed MB, desmoplastic

subtype. The midline 4th

ventricle is the 2nd most

common location for

desmoplastic MBs and the

most common site for classic

MBs. Histopathology disclosed

desmoplastic MB, Sonic

hedgehog subtype.

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Pineocytoma

KEY FACTS

TERMINOLOGY

• Pineocytoma (PC), pineal parenchymal tumor (PPT)

• PCs are composed of small, uniform, mature cells

○ Cells resemble pineocytes

IMAGING

• General features: Circumscribed, enhancing pineal mass

○ May mimic benign pineal cyst or PPT of intermediate

differentiation (PPTID)

○ Typically < 3 cm

○ May compress adjacent structures

○ Rarely extends into 3rd ventricle, rarely invasive

○ Can compress aqueduct → hydrocephalus

• CT

○ Circumscribed iso-/hypodense pineal region mass

○ Peripheral ("exploded") Ca++ common

○ CECT: Enhances (solid, ring, nodular)

• MR (most sensitive)

○ Cystic change may be present

○ Enhancement may be solid or peripheral

TOP DIFFERENTIAL DIAGNOSES

• Nonneoplastic pineal cyst

• PPTID

• Pineoblastoma

• Germinoma, other germ cell tumors

CLINICAL ISSUES

• Headache, dorsal midbrain (Parinaud) syndrome most

common features

• Increased intracranial pressure, ataxia, hydrocephalus,

mental status changes may occur

• Most common in adults, mean 40 years

• Stable or slow-growing tumor

• Germ cell markers (α-fetoprotein, hCG) absent

• Surgical excision or stereotactic biopsy is primary treatment

○ Complete surgical resection generally curative

(Left) Sagittal graphic shows a

cystic pineal gland mass ﬈

with a fluid-fluid level and

nodular tumor along the

periphery of the mass, typical

of pineocytoma. No significant

mass effect is present.

Pituicytomas may be found

incidentally or present with

hydrocephalus. (Right) Axial

NECT shows a classic example

of a pineocytoma. Note the

"exploded" peripheral

calcification ſt in this small

mass that arises from the

pineal region. The tumor is just

over 1 cm in size. There is no

hydrocephalus.

(Left) Sagittal T1 MR of a 50-

year-old woman with

headache shows a cystic

pineal region mass ſt with

associated ventriculomegaly

st and local mass effect on

the tectum ﬊. Mass effect on

the superior tectum often

results in dorsal midbrain

(Parinaud) syndrome. (Right)

Axial FLAIR MR in the same

patient shows the

hyperintense, lobular pineal

region mass ſt with

associated ventriculomegaly.

Pineocytoma was diagnosed

at resection. These WHO

grade I tumors are often

stable for years.

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