neoplasms of the brain

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C HAPTER 3

58

C HAPTER 3

Neoplasms of the Brain

The World Health Organization (WHO) classification of tumorsof the brain remains the worldwide standard. Members of the

International Society of Neuropathology, International Academyof Pathology, and Preuss Foundation for Brain Tumor Researchmet in Lyon, France, and subsequently produced the mostwidely used classification of brain tumors, one that we will sharewith you in this book.

The essential distinction that a neuroradiologist must make iswhether a lesion is intra-axial (intraparenchymal) or extra-axial(outside the brain substance; i.e., meningeal, dural, epidural, orintraventricular). This distinction has been made easier by themultiplanar capabilities of magnetic resonance (MR) imaging.The quintessential and most common extra-axial mass is themeningioma, a readily treatable and diagnosable lesion. Themeningioma is not only extra-axial, but also intradural. Extra-axial intradural lesions buckle the white matter, expand the ipsi-lateral subarachnoid space, and sometimes cause reactive bony

changes. On MR scans you can visualize the dural margin anddetermine that the lesion is extra-axial. The prototypical extra-dural (epidural) extra-axial mass, a bone metastasis, displacesthe dura inward (is superficial to the dural coverings) but oth-erwise may have the same contour as an intradural extra-axialmass (Fig. 3-1).

When you are confronted with a solitary intra-axial mass in anadult, the odds are nearly even that the lesion is either a solitary

metastasis or a primary brain tumor. Fifty percent of metastases tothe brain are solitary, so the lack of multiplicity should not dissuadeyou from considering a metastasis in the setting of a single intra-axiallesion. You can classify a lesion as intra-axial if (1) it expands the cor-tex of the brain; (2) there is no expansion of the subarachnoid space;(3) the lesion spreads across well-defined boundaries; and (4) thehypointense dura and pial blood vessels are peripheral to the mass.

Occasionally, the distinction between intra-axial and extra-axiallesions may be blurred, because some extra-axial lesions (aggres-sive meningiomas, dural metastases) may aggressively invade theunderlying brain. Conversely, an intra-axial lesion may invade themeninges. Although the latter is somewhat atypical, it has beendescribed in neoplasms such as lymphoma, glioblastoma multi-forme, and parenchymal metastases.

You must localize a lesion as intra-axial or extra-axial so your

differential diagnosis will be relevant. Once you have made thatdecision, you must appreciate its other qualities: its shape (mar-gination), its consistency (solid, hemorrhagic, calcified, fatty,cystic), its colors (density and intensity), and its enhancement.These are the secondary features in intra-axial and extra-axiallesions that allow you to arrive at the specific diagnosis.

FIGURE 3-1. Extra-axial lesion signs. A, A skull-based extradural mass is depicted diagrammatically, producing a meniscus sign, displacement of thesubarachnoid veins inward, and buckling of the gray-white interface. Dura may be seen stretched over the mass. B, Extra-axial mass. The classic extra-axial mass (M) expands the subarachnoid space at its borders ( straight arrows), has a dural base (arrowheads), and displaces blood vessels in the subarach-noid space medially (curved arrow). This was a vestibular schwannoma, but on the top image it could just as easily be a meningioma with that dural base.Notice the extension into the internal auditory canal on the lower image (open arrow).

A

B

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NEOPLASMS OF THE BRAIN 59

EXTRA-AXIAL TUMORS

Tumors of the Meninges

MeningiomasMeningiomas constitute the most common extra-axial neoplasmof the brain (Box 3-1). This lesion commonly affects middle-agedwomen. However, because of its incidence, it represents a signifi-cant proportion of the extra-axial neoplasms in men and in adultsof all age groups. The most common locations for meningioma (in

descending order) are the parasagittal dura, convexities, sphenoidwing, cerebellopontine angle cistern, olfactory groove, and planumsphenoidale. Ninety percent occur supratentorially. One percentof meningiomas occur outside the central nervous system (CNS),presumably from embryologic arachnoid rests. The most commonsites for these “extradural” meningiomas are the sinonasal cavity,

parotid gland, deep tissues, and skin. Because meningiomas arisefrom arachnoid cap cells, they can occur anywhere that arachnoidexists.

On unenhanced computed tomography (CT) scans, approximately 60% of meningiomas are slightly hyperdense comparedwith normal brain tissue (Fig. 3-2). You may see calcificationwithin meningiomas in approximately 20% of cases. Rarelycystic, osteoblastic, chondromatous, or fatty degeneration omeningiomas occurs. The specific histologic subtypes of meningioma—transitional, fibroblastic, and syncytial—cannot be readily distinguished on imaging.

Magnetic resonance imaging is superior to CT in detectingthe full extent of meningiomas, sinus invasion or thrombosisvascularity, intracranial edema, and intraosseous extension. Thetypical MR signal intensity characteristics of meningiomas consist of isointensity to slight hypointensity relative to gray matteon the T1-weighted image (T1WI) and isointensity to hyperintensity relative to gray matter on the T2-weighted image(T2WI). The “cleft sign” has been described in MR to identify extra-axial intradural lesions such as meningiomas. The clefusually contains one or more of the following: (1) cerebrospinafluid (CSF) between the lesion and the underlying brain parenchyma, (2) hypointense dura (made of fibrous tissue), and (3marginal blood vessels trapped between the lesion and the brainOne may see vascular flow voids on MR within and around a

meningioma. Avid enhancement after contrast is also seen (Fig3-3), but occasionally meningiomas may have necrotic centers ocalcified portions, which may not enhance. With MR you may beable to identify the dural tail , enhancement of the dura trailingoff away from the lesion in crescentic fashion, which is typicaof meningiomas and has been exhibited in up to 72% of case(Fig. 3-4). There has been a debate in the radiologic literatureas to whether the dural tail always represents neoplastic infil-tration of the meninges by the meningioma or, alternatively, areactive fibrovascular proliferation of the underlying meningesIn the typical situation where a differential diagnosis of vestibular schwannoma, meningioma, or fifth nerve schwannoma isdebated, the dural tail may be a useful sign to suggest menin-gioma rather than other diagnoses (Table 3-1). The dural tail i

B OX 3-1. WHO Classification of Tumors of theMeninges

TUMORS OF MENINGOTHELIAL CELLSMeningioma

MeningothelialFibrous (fibroblastic)Transitional (mixed)PsammomatousAngiomatousMicrocysticSecretoryLymphoplasmacyte-richMetaplasticClear cellChordoidAtypicalPapillaryRhabdoid

Anaplastic meningioma

MESENCHYMAL, NONMENINGOTHELIAL TUMORS

LipomaAngiolipomaHibernomaLiposarcomaSolitary fibrous tumorFibrosarcomaMalignant fibrous histiocytomaLeiomyomaLeiomyosarcomaRhabdomyomaRhabdomyosarcomaChondromaChondrosarcomaOsteomaOsteosarcomaOsteochondromaHemangiomaEpithelioid hemangioendotheliomaHemangiopericytomaAngiosarcomaKaposi sarcoma

PRIMARY MELANOCYTIC LESIONSDiffuse melanocytosisMelanocytomaMalignant melanomaMeningeal melanocytosis

TUMORS OF UNCERTAIN HISTIOGENESISHemangioblastoma

FIGURE 3-2. Meningioma. Axial unenhanced computed tomography scanshows a hyperdense (arrows) extra-axial mass in the middle cranial fossa.




60 Neuroradiology: The Requisites

not usually seen with schwannomas, although dural metastasesmay demonstrate a similar finding.

Meningiomas may encase and narrow adjacent vessels. Thisfinding helps in the sella region, because pituitary adenomas, theother culprit in this location, virtually never narrow the cavernouscarotid artery.

The degree of parenchymal edema is variable in menin-giomas. Although it is true that larger meningiomas tend to havea greater degree of parenchymal edema, there are exceptions,in which smaller meningiomas incite a large amount of whitematter edema. The degree of edema seems to correlate withlocation, because meningiomas adjacent to the cerebral cortextend to incite greater edema than those along the basal cisternsor planum. Edema associated with meningiomas may be causedby compressive ischemia, venous stasis, aggressive growth, orparasitization of pial vessels. Venous sinus occlusion or venousthrombosis can also cause intraparenchymal edema from ameningioma.

Intraosseous meningiomas may appear as expansions of theinner and outer tables of the calvarium or may even extend into

the scalp soft tissues (Fig. 3-5). No dural component may bepresent at all. This type of meningioma strongly resembles ablastic osseous metastasis. Intraventricular meningiomas typi-cally occur around the choroid plexus (80%) in the trigone ofthe lateral ventricle and have a distinct propensity for the leftlateral ventricle (Fig. 3-6). Only 15% of intraventricular menin-giomas occur in the third ventricle, and 5% occur in the fourthventricle. Intraventricular meningiomas calcify in 45% to 68%of cases, and their frequency is higher in children. Multiplemeningiomas are associated with neurofibromatosis type 2(NF-2).

Bony changes associated with meningiomas may be hyperost-otic or osteolytic and occur in 20% to 46% of cases. Hyperostosisis particularly common when the tumor is at the skull base oranterior cranial fossa, and here it may resemble fibrous dysplasiaor Paget disease. The presence of bony reaction may be a help-

ful feature to distinguish meningiomas from other extra-axialmasses, particularly schwannomas, which do not elicit a bonyreaction. Bony changes, according to the neuropathology lit-erature, may be due to actual tumor infiltration of the marrowspace with osteoblastic metaplasia or merely due to the involveddura inciting hypervascularity of the periosteum and subsequentbenign osteogenesis. Therefore, if the hyperostosis is along theinner table only, you cannot say whether it is due to neoplasticinvasion or reactive changes. If the outer table is transgressed,tumor is most likely.

Meningiomas are one of the few tumors where angiography stillmay play an important role. Meningiomas diagnostically appearas lesions with an angiographic stain (tumor blush) and have bothdural and pial blood supply. The characteristics of the stain are

B

A

FIGURE 3-3. Parasagittal meningioma. A, This meningioma is really darkon T2-weighted image but the adjacent bright cerebrospinal fluid (CSF)demonstrates its extra-axial location nicely (CSF cleft sign designated byarrows). B, Add a dural tail (arrows) and strong enhancement, and youshould be dictating this case as a meningioma.

FIGURE 3-4. Another piece of tail in a meningioma. Coronal enhancedT1-weighted image of this tentorial meningioma shows enhancing tails(arrowheads) coursing medially and laterally from the main portion of thetumor. Note that tumor extends to either side of the tentorium.

TABLE 3-1. Differential Diagnosis of Meningiomaversus Schwannoma

Feature Meningioma Schwannoma

Dural tail Frequent Extremely rare

Bony reaction Osteolysis orhyperostosis

Rare

Angle made with dura Obtuse Acute

Calcification 20% Extremely rare

Cyst/necrosis formation Rare Up to 10%

Enhancement Uniform Inhomogeneous in 32%

Extension into theinternal auditory canal

Rare 80%

MRS Alanine Taurine, GABA

Precontrast CTattenuation

Hyperdense Isodense

Hemorrhage Rare Somewhat more common

CT, computed tomography; GABA, gamma-aminobutyric acid; MRS, magneticresonance spectroscopy.





classically compared with an unwanted guest who comes earlyand stays late. Depending on the location of the tumor, you mayhave to perform internal carotid, external carotid, and vertebrainjections (Table 3-2). In the typical convexity or sphenoid wingmeningioma, the middle meningeal artery is enlarged (seen byprimitive radiologists before angiography as enlarged meningeagrooves on the lateral skull film). At present preoperative embolization of meningiomas is sometimes performed to decrease thevascularity of the tumor. Make your referring neurosurgeon’

day by decreasing the intraoperative blood loss. Polyvinyl alcohol particles are most commonly used as the embolant (100 to250 micromillimeters in size), but Gelfoam, cyanoacrylate, andtrisacryl gelatin microspheres (Embospheres) are also employedby some.

Skull base meningiomas in particular often require preoperative embolization. The skull base is the one region wheremeningiomas can become unresectable because of collateradamage to vital structures (e.g., the cranial nerves and carotidartery in the cavernous sinus meningioma, the vertebrobasilavessels for foramen magnum lesions, the optic nerves at theoptic canal).

On magnetic resonance spectroscopy (MRS), meningiomas arecharacterized by high levels of alanine and absent N-acetyl aspartate (NAA). No glutamine is seen. One can use the presence o

FIGURE 3-5. Osseous involvement by meningioma. Enhanced T1-weighted image demonstrates evidence of an osseous meningioma expand-ing the left calvarium outward as well as inward. Arrows depict the duraltail on either side of this lesion. There is a soft-tissue component extend-ing under the galeal layer.

A

B C

FIGURE 3-6. Intraventricular meningioma. A, SagittalT1-weighted image shows a well-defined large mass ina dilated left lateral ventricular trigone. B, The mass,typical of a meningioma, is isointense to gray matter. It iscentered on the choroid. C, Classic meningioma!





taurine or gamma-aminobutyric acid in schwannomas to distin-guish meningiomas from schwannomas.

Atypical Meningioma Atypical meningiomas are classified as WHO grade II. His-topathologically they must have increased mitotic rates (fouror more mitoses per 10 high power field [hpf]) or small cellswith high nucleus/cytoplasm ratio, prominent nucleoli, sheet-like growth, and foci of necrosis. Accordingly, 2.4% of menin-giomas are thereby classified as atypical and these tumors havelower apparent diffusion coefficient (ADC) values on diffu-sion-weighted images (DWI) than typical meningiomas. Theyrecur more frequently. They look radiographically like benignmeningiomas.

Malignant MeningiomasMalignant meningiomas (WHO grade III) occur uncommonlyand are usually diagnosed when a meningioma exhibits intra-parenchymal invasion or markedly rapid growth. Histo-pathologically they are defined by malignant cytology, 20 ormore mitoses/hpf, or sarcomatous degeneration. They, as well,have restricted diffusion compared to benign meningiomas.They most likely arise from benign tumors gone awry and mayaggressively invade the brain. The papillary variety of menin-gioma undergoes malignant differentiation more commonlythan the rest. Anaplasia may occur, accounting for the classifi-cation of Simpson’s grade III meningiomas. The higher gradeis associated with a higher rate of recurrence. Survival varieswith the site, size, grade, and extent of surgical removal of thetumor.

Radiation-induced Meningioma Radiation therapy induces five times more meningiomas thanit does gliomas or sarcomas. The diagnosis of radiation-inducedmeningioma is made if the meningioma arises in the radiationfield, appears after a latency period (of years), was not the pri-mary tumor irradiated, and is not seen in a patient with neuro-fibromatosis. These tumors have been associated with low-doseradiation treatment for tinea capitis and have mean latency peri-ods of approximately 35 years. Multiple meningiomas occur inup to 30% of previously irradiated patients with meningiomasand in 1% to 2% of nonirradiated patients with meningiomas.Recurrence rates are higher in radiation-induced meningiomasthan in nonradiation-induced tumors.

The differential diagnosis of primary tumors that mimic men-ingiomas is broad (see Box 3-1).

Mesenchymal Meningeal TumorsAs noted in Box 3-1, there are a number of mesenchymal tumorsthat can affect the meninges. These are all relatively rare lesions,which may have either osseous (e.g., osteoma, osteosarcoma),chondroid (e.g., chondroma, chondrosarcoma), muscular (e.g.,leiomyoma, rhabdomyosarcoma), fatty (e.g., lipoma, liposar-

coma), or fibrous (e.g., fibroma, malignant fibrous histiocytoma)matrices associated with them. If you remember that the fibrousfalx can be ossified (with bone and marrow fat), you can recallthese tumors more readily.

Hemangiopericytoma The term angioblastic meningioma has been replaced by heman-

giopericytoma in the new WHO classification of meningeal mes-enchymal tumors. These tumors, derived from smooth musclepericyte cells around the capillaries of the meninges, are moreaggressive than most meningiomas, have a higher rate of recur-rence, and can metastasize. Hence some consider them malig-nant, and most say they are distinct from meningiomas. Theytend to be large (over 4 cm in size), lobular, and extra-axialsupratentorial masses. Hydrocephalus, edema, and mass effect

are not uncommon with this entrée. Precontrast CT shows het-erogeneous, hyperdense tumors that enhance. Hyperostosis orcalcification is rare. Hemangiopericytomas affect men more thanwomen, unlike most MENingiomas.

MeningioangiomatosisMeningioangiomatosis is a rare bird indeed, straddling the intra-parenchymal and extraparenchymal domain with a lesion thatcan invlove the cortex (90%) or meninges. Most often associatedwith NF-2, it grows slowly and contains calcification. Intracorticalfoci of proliferating small vessels and fibroblasts accompany themeningeal process. Cysts may coexist. The entity is seen in theyoung and is a potential source for seizures owing to its corticallocation.

Melanocytic LesionsWithin this category one finds diffuse melanocytosis, mel-anocytoma, neurocutaneous melanosis, and malignant mela-noma. The melanin-containing cells are leftovers from neuralcrest origin. These diagnoses are difficult to make becausemetastatic melanoma to the dura does occur and must oftenbe excluded. The melanocytoma is the most common of thelot and is seen in adults, whereas melanocytosis is more of apediatric disorder (see Fig. 9-53). Although the latter is a dif-fuse process, the former usually presents as a posterior fossamass. Hyperintensity on T1WI is the only hope for sealing thisdiagnosis, but the presence of this finding varies with melanincontent. Spread of melanocytosis through the Virchow-Robinspaces is possible.

Malignant melanoma of the meninges may bleed or spread fromthe dura to the adjacent nerves, brain, or skull. Neurocutaneous

melanosis shows melanocytic nevi of the skin (especially aboutthe face), syringomyelia, and CNS lipomas. Prognosis is pooras is that for malignant melanoma of the meninges with distantmetastases.

Tumors of Neurogenic Origin

SchwannomasThe three neurogenic tumors (schwannomas, neurofibro-mas, and neuromas), are similar in appearance. Histologicallyschwannomas arise from the perineural Schwann cells. Thesecells may differentiate into fibroblastic or myelin-producingcells. Two types of tissue may be seen with schwannomas:Antoni A and Antoni B tissue. The Antoni A tissue consists

TABLE 3-2. Blood Supply to Meningiomas

Location of Meningioma

Commonly Seen Blood Supply(Origin of Vessel)

Convexity Middle meningeal artery (ECA)Artery of the falx (branch of

ophthalmic artery)

Sphenoid wing Middle meningeal artery (ECA)

Tentorium andcerebellopontine angle

Tentorial artery (artery of Bernasconi-Casanari) from meningohypophysealtrunk (ICA)

Olfactory groove Branches from ophthalmic artery

Foramen magnum andclivus

Anterior meningeal artery (vertebral)Dorsal meningeal artery from

meningohypophyseal trunk (ICA)

Posterior fossa dura and falxcerebelli

Posterior meningeal artery (vertebraland MMA or ascending pharyngealbranches)

ECA, external carotid artery; ICA, internal carotid artery; MMA, middle meningealartery.





of densely packed palisades of fibrous and neural tissue andtypically has a darker signal on T2WI because of the compact-ness of the fibrils. Antoni B tissue is a looser, myxomatous tis-sue that is typically brighter on T2WI. Note that, dependingon the degree of Antoni A and B tissue within schwannomas,the signal intensity of these lesions may directly simulate thatof meningiomas. Other terms used for schwannomas includeneurilemmomas and neurinomas, but the most accurate term is

schwannoma.

Cellular, plexiform, and melanotic varieties of schwannomashave been described. Fifty percent of patients with psammoma-tous melanotic schwannomas have Carney complex, a syndromecharacterized by facial pigmentation, cardiac myxomas, and endo-crinologic disorders, including Cushing syndrome, acromegaly,pheochromocytoma, or adrenal hyperplasia (NAME syndrome:nevi, atrial myxoma, mucinosis of skin, and endocrine overac-tivity). More than 10% of melanotic schwannomas may becomemalignant. Malignant schwannomas may also be seen in patientswith NF-1.

The distinction between meningiomas and schwannomas is acommon one that radiologists must make (see Table 3-1). In someinstances it is impossible to distinguish between the two. Bothmeningiomas and schwannomas may track along the course of thenerves; therefore the extent of the tumor is not helpful in distin-

guishing the two. As described previously, the dural tail is a help-ful sign in suggesting a diagnosis of meningioma. In 81% of casesthe border of a vestibular schwannoma makes an acute angle withthe petrous bone; meningiomas usually make an obtuse angle.A curious finding has been described with vestibular schwanno-mas; arachnoid cysts coexist in 7% to 10% of cases, usually withthe larger tumors (Fig. 3-7). These must be distinguished fromcystic degeneration (and preponderance of Antoni B tissue) of thetumor, which is also a frequent phenomenon. Schwannomas maytherefore be very bright on a T2WI, unusual for meningiomas.Vestibular schwannomas show microhemorrhages on suscepti-bility weighted scans in a high proportion—something absent inmeningiomas.

One of the features distinguishing vestibular schwannomasfrom meningiomas is the expansion of the internal auditory canal(IAC) seen in schwannomas. The porus acusticus (the bony open-ing of the IAC to the cerebellopontine angle cistern) is typicallyflared and enlarged with vestibular schwannomas, whereas the

amount of tissue seen in the IAC with meningiomas is usuallysmall or absent. Vestibular schwannomas account for more than90% of purely intracanalicular lesions, but only 5% to 17% of themare solely intracanalicular (Fig. 3-8). Approximately 10% to 20%of vestibular schwannomas present only in the cerebellopontineangle cistern without an IAC stem (Box 3-2). Approximately 75%of vestibular schwannomas have a canalicular and cisternal portion (Fig. 3-9).

On MR, schwannomas are usually isointense to slightly hypointense compared with pontine tissue on all pulse sequencesEnhancement is nearly always evident and homogeneous inapproximately 70% of cases. Peritumoral edema may be seen inone third of cases, usually in the larger schwannomas. Less common

features of schwannomas include calcification, cystic change, andhemorrhage. Subarachnoid hemorrhage is a rare presentation ovestibular schwannomas. Hydrocephalus may occur due to maseffect or obstruction of CSF outflow at the arachnoid villi level from“humours” from the “tumours.”

Schwannomas occur most commonly along cranial nerve VIIIThe superior vestibular branch of cranial nerve VIII is the moscommon origin of the vestibular schwannoma (not “acousticneuromas”), slightly more common than the inferior vestibula

FIGURE 3-7. Vestibular schwannoma with arachnoid cyst. A cyst (C) asso-ciated with enhancing acoustic schwannoma (T) is seen on this enhancedT1-weighted image.

FIGURE 3-8. Left intracanalicular vestibular schwannoma. Postgadoliniumenhanced T1-weighted coronal scans show an intracanalicular mas(arrows) on the left side. Perform a fat-saturated scan to ensure that thidoes not represent fat.

B OX 3-2. Cerebellopontine Angle Masses

Vestibular schwannoma (75%)Meningioma (10%)Epidermoid (5%)Facial nerve schwannoma (4%)Aneurysm (vertebral, basilar, posterior inferior cerebellar

artery)Brain stem gliomaArachnoid cystParagangliomaHematogeneous metastasisSubarachnoid spread of tumorsLipomaHemangiomaChoroid plexus papillomaEpendymomaDesmoplastic medulloblastoma





nerve. Nonetheless, patients typically have hearing loss. Afterlesions of cranial nerve VIII, schwannomas of cranial nerves VII(Fig. 3-10) and V are the most common site of intracranial neu-rogenic tumors, although ANY cranial nerve may be involved(Fig. 3-11).

Postoperatively, it is not unusual to see linear gadolin-ium enhancement in the IAC after vestibular schwannomaresection as dural reaction. This can be followed expec-tantly. For those cases with progressive, nodular, or masslikeenhancement, more careful follow-up is required to excluderecurrence.

Trigeminal schwannomas may arise anywhere along thepathway from the pons to Meckel’s cave to the cavernoussinus, to and beyond the exit foramina (ovale, rotundum, andsuperior orbital fissure). Outside the brain, the schwannomasof cranial nerve V most commonly occur along the second divi-sion. These tumors present with facial pain that is burning innature.

Jugular schwannomas more commonly grow intracraniallythan extracranially and typically smoothly erode the jugularforamen. The border of the bone is sclerotic, as opposed to the

paraganglioma, which has a much more irregular and nonscleroticmargin. Schwannomas compress the jugular vein, whereas para-gangliomas (glomus jugulare tumors) invade the vein. Growthinto the posterior fossa is the rule. Jugular foramen schwanno-mas most commonly present with hearing loss and vertigo ratherthan cranial nerve IX symptoms. Whether the schwannomaarises from one cranial nerve or the next, the imaging appear-ance is similar.

NeurofibromasNeurofibromas, strictly speaking, refer to the tumors associatedwith neurofibromatosis. They are classified as WHO grade I,and all ages and sexes are represented. They may occur sporadi-cally as well, though less commonly than schwannomas. The skinand subcutaneous tissues are affected more often than periph-eral nerves; spinal nerve neurofibromas are rare, and cranial nerve

FIGURE 3-9. Cerebellopontine angle and intracanalicular vestibularschwannoma. Note the brightly enhancing mass with both a cisternal

(open arrow) and intracanalicular (arrowheads) portion. The ipsilateral pre-pontine cistern is enlarged.

A B C

FIGURE 3-10. Facial nerve schwannoma. A, Sagittal T1-weighted image (T1WI) shows a markedly thickened descending portion of the facial nerve(arrows). B, The mass is difficult to appreciate on the coronal T2WI were it not for the well-placed arrows delineating its course. (This is a new feature onthe Geimensillip scanner.) C, The course of this enhancing mass suggests a facial nerve schwannoma by virtue of its tympanic segment and descendingportion ( star ).

FIGURE 3-11. Fourth nerve schwannoma. FLAIR image through thebrain stem demonstrates an extra-axial mass along the right side of theupper pons. One can faintly see the normal fourth cranial nerve (openarrows) on the left side coursing around the brain stem. The right-sidedlesion ( solid arrows) represents a fourth nerve schwannoma.





involvement is uncommon. These lesions contain Schwann cells,perineural cells, and fibroblastic cells and may occur in a plexi-form aggressive subtype, which appears as a network of diffuselyinfiltrating masses. Once again, Antoni A or B tissue may pre-dominate in the lesion and will alter the T2WI characteristics.Do not think about neurofibromas for NF-2, only NF-1. NF-2is a misnomer. Classically, in “neurofibromatosis” type 2 bilat-

eral vestibular schwannomas are seen. Plexiform neurofibromasin the cranial nerves or peripheral nervous system may occurin NF-1 and are one of the seven criteria for diagnosis of this

disorder. Plexiform neurofibromas, because of their extensiveness, can be distinguished from neuromas and schwannomasThey are generally found in the extremities or in the soft tissueof the head and neck. They have a significant rate of malignandedifferentiation.

Classic descriptions say that neurofibromas can sometimes bedistinguished from schwannomas by their eccentricity and morefibrous tissue signal on MR, but in many cases the two look thesame.

NeuromasBy strict pathologic definition neuromas refer to a posttraumatic proliferation of nerve cells rather than a true neoplasmThe perineural lining and fibroblastic tissue seen in the othelesions just described are not present. These lesions are less common than schwannomas. They are usually seen in the cervicaspine when nerves are avulsed or in an operative bed. Again, onemust know where to look for these lesions. Unfortunately, in thecommon vernacular most people mean “schwannoma” whenthey say “neuroma” (e.g., “acoustic neuroma,” which is a doublemisnomer as these are truly “vestibular” lesions). On scanningthese masses look like small schwannomas.

Metastases

Dural MetastasesDural metastases usually spread out along the dura as hematogenously disseminated en plaque lesions from extracranial primarytumors (Fig. 3-12). Lung, breast, and prostate cancer, as well amelanoma, are known to produce dural metastases. Some of thedural metastases may arise from spread of adjacent bone metastases. Breast carcinoma is the most common neoplasm to be associated with purely dural metastases. Lymphoma is next moscommon but is unique in that the dural lymphoma may be theprimary focus of the neoplasm (Fig. 3-13). Dural plasmacytomawill look nearly identical to dural lymphoma (Fig. 3-14). In children dural metastases are most commonly associated with adrenal neuroblastomas and leukemia. These tumors are also famoufor lodging in the cranial sutures, widening them in an infant.

Occasionally, one can identify an adjacent parenchymal metas

tasis with dural spread (Fig. 3-15); alternatively, an osseousdural metastasis (breast, prostate primaries) occasionally invadethe parenchyma (Fig. 3-16). On MR the T1WI and T2W

FIGURE 3-12. Metastasis with a dural tail. Postgadolinium-enhancedT1-weighted scan in a patient with adenocarcinoma of the lung demon-strates a metastasis peripherally in the right temporal lobe. Although adural tail (arrows) is suggestive of a meningioma, it is not pathognomonicfor it.

A B

FIGURE 3-13. Dural lymphoma. A, See the low signal dural mass on the T2-weighted image that is eliciting the intraparenchymal edema? NoB, Then you cannot miss it on the enhanced scan. Lymphoma will nearly always enhance (unless the neurosurgeons are reluctantly treating it withmassive doses of steroids). Include meningioma, sarcoidosis, plasmacytoma, and other dural metastases in the differential diagnosis.





characteristics are variable; however, typically the lesion ishypointense on T1WI and hyperintense on T2WI (Fig. 3-17 asan exception to the rule). On CT these lesions are identified asisodense thickening of the meninges. Contrast enhancement is

prominent. This is a diagnosis where contrast-enhanced T1WI orfluid-attuenuated inversion recovery (FLAIR) scans can readilydemonstrate the abnormality.

Inflammatory lesions that may simulate dural metastasesinclude granulomatous infections (mycobacterial, syphilitic, andfungal), Erdheim-Chester disease, sarcoidosis, and Langerhanscell histiocytosis.

Subarachnoid SeedingUsually one is dealing with tiny nodules of implanted tumorseedings. When the process is diffuse we use the term sugar-coating of the subarachnoid space because the whole pial surfaceis studded with sugar granules. A combination of sugar-coatingand focal nodules may also occur. Subarachnoid seeding mayoccur with primary CNS tumors or primary tumors of other ori-gins (Table 3-3). Lymphoma and leukemia are the most com-

mon tumors to seed the CSF. However, because they only rarelyinvade the meninges and do not incite reactions in the CNS,lymphomatous clusters are infrequently identified by neuroim-aging techniques; the diagnosis is usually made by multiplespinal taps for CSF sampling. CSF seeding is associated with amean survival of 1 to 2 months without and 6 to 10 months withtreatment. The differential diagnosis could include arachnoidi-tis, Guillain-Barré syndrome, sarcoidosis, infectious granuloma-tous meningitides, Lyme disease, and cytomegalic inclusionvirus (CMV) radiculitis.

When a lesion has spread to the subarachnoid space, you maysee it only on contrast-enhanced studies, and MR is much moresensitive than CT. However, unenhanced and enhanced FLAIRimaging has been shown to be increasingly effective at identi-fying subarachnoid disease, including metastatic disease. The

malignant cells in the CSF or the associated elevated protein inthe CSF will cause the usually low signal of CSF to be bright on aFLAIR scan. Although this may be a difficult diagnosis to make inthe basal cisterns where “f” (FLAIR and flow) artifacts abound,the presence of such high signal over the convexities impliessubachnoid seeding, subarachnoid hemorrhage, or meningealinflammation. FLAIR may even be positive in lymphoma and

A B

FIGURE 3-14. Plasmacytoma of the dura. A, The gadolinium-enhanced scan looks just like one would expect for a menin-gioma with marked enhancement and a dural-based lesion.The irregular margins (saw-toothed appearance) suggesting pialspread would be funky for a meningioma though. B, Even theT2-weighted image shows low signal that simulates a menin-

gioma or lymphoma or sarcoidosis. The way to score on this shotis to have a history of a plasma cell dyscrasia.

FIGURE 3-15. Leiomyosarcoma with dural-based metastasis. Postgado-linium coronal scan shows a high left frontal intraparenchymal metastasis,which demonstrates dural invasion (arrows) along its superomedial margin.(Ignore the phase-ghosting artifact.)

A

FIGURE 3-16. Intraparenchymal growth of renal cell carcinoma metastasis. A, T1-weighted scans show a lesion (L) centered on the calvarium withextracalvarial as well as epidural spread. B, The T2-weighted scan again demonstrates the center of the lesion to be at the bone. C, However, with con-trast, at a more inferior location, there is a medial nodule, which extends through the dura into the intraparenchymal compartment (open arrows). Duralenhancement more peripherally is denoted by small black arrows.





leukemia, where enhanced scans fail most dramatically. FLAIRwith contrast enhancement increases the yield even higher!

The typical locations where one identifies subarachnoid seed-ing are at the basal cisterns, in the interpeduncular cistern, at thecerebellopontine angle cistern, along the course of cranial nerves,and over the convexities (Fig. 3-18). One may see various manifes-tations of subarachnoid seeding, including the sugar-coated linearappearance to the enhancement of the surface of the brain (espe-cially cerebellum) and spinal cord, or a nodular appearance of tumordeposits on nerve roots, both cranial and spinal. Often one identifies

a peripheral intraparenchymal metastasis contiguous with the duralsurface of the brain, from which cells are shed into the CSF. Withsubarachnoid seeding secondary hydrocephalus may be present.

The other terms you will see for the same entity include meningeal carcinomatosis or carcinomatous meningitis. Clinically the patientspresent with multiple cranial neuropathies, radiculopathies, ormental status changes secondary to hydrocephalus or meningealirritation. The cranial neuropathies may be irreversible. Althoughan initial CSF sample is positive in only 50% to 60% of cases, byperforming multiple taps the positive cytology (and headache) rateapproaches 95%. Patient survival is usually less than 6 months withthis finding except in cases of hematologic malignancies. Breastcancer, lung cancer, and melanoma are the most common non-CNS primaries to seed the CSF.

ChloromaGranulocytic sarcoma (chloroma) is a tumor of immature granu-locytes found in association with myelogenous leukemias. Thisoft-tissue mass can occur virtually anywhere and may predatethe diagnosis of leukemia. In the CNS, the orbit and epiduraspace are affected most commonly, but dural infiltration or even

intra-axial involvement may be seen. The lesion, though eliciting bright vasogenic edema, may be intermediate intensity onT2WI, thought to be due to the high concentration of myeloper-oxidase. It enhances. The term chloroma refers to its greenish coloakin to chlorophyl. Chloromas portend a blast crisis. They areradiosensitive.

Choroid Plexus Masses

Choroid Plexus PapillomaChoroid plexus papillomas (WHO grade I) comprise 3% of intracranial tumors in children and 10% to 20% of those presenting inthe first year of life. Eighty-six percent of these tumors are seenin patients less than 5 years old. In children 80% occur at the

A B

FIGURE 3-17. Mucinous adenocar-cinoma metastatic to the dura. A, Coronal unenhanced T1-weightedimage (T1WI) shows a dural-basedmass with low signal centrally and

peripheral high signal intensity(arrowheads). The lesion was cal-cified on computed tomography.(Obsearvant readers will note thesubcutaneous sebaceous cyst inthe right upper part of the scalp.)B, On axial T2WI the lesion haslow intensity but incites high signalintensity edema.

FIGURE 3-18. Subarachnoid seeding from a brain stem glioma. Postcontrast T1-weighted image shows contrast-enhancing nodules (arrowsin the roof of the lateral ventricle and in the superior vermian cistern. Thekeen observer will notice the “overly pregnant” belly of the pons.

TABLE 3-3. Sources of Subarachnoid Seeding

CNS Primary Non-CNS Primary

Children

Medulloblastoma (PNET) Leukemia/lymphomaEpendymoma (blastoma = PNET) NeuroblastomaPineal region tumorsMalignant astrocytomasRetinoblastomaChoroid plexus papilloma

Adults

Glioblastoma multiforme Leukemia/lymphomaPrimary CNS lymphoma BreastOligodendroglioma Lung

Melanoma

Gastrointestinal

Genitourinary

PNET, primitive neuroectodermal tumor.





trigone or atria of the lateral ventricles; in adults they are usuallyseen in the fourth ventricle. Overall, 43% are located in the lateralventricle, 39% the fourth ventricle, 11% the third ventricle, and7% in the cerebellopontine angle cistern. Multiple sites are pres-ent in 3.7% of cases. If they are seen at the foramen of Luschka,it may be due to extension from the fourth ventricle or the cer-ebellopontine angle cistern, or from primary involvement in thislocation from a choroidal tuft. Simian virus 40 (SV40) has beenimplicated in the evolution of these tumors. This same virus has

been implicated in ependymomas.The tumors present with hydrocephalus and papilledema caused

by overproduction of CSF (four to five times normal) or obstructive

hydrocephalus caused by tumor, hemorrhage, high-protein CSF, oradhesions obstructing the ventricular outlets. Lately, the obstruc-tionists have gained the majority from the overproductionists as faras the explanation for hydrocephalus. Calcification occurs in 20%to 25% of cases, and hemorrhage in the tumor is seen even morefrequently than calcification. Choroid papillomas are typicallyhyperdense on unenhanced CT, with a mulberry appearance.Tumors are usually of low signal on T1WI and mixed intensity onT2WI unless hemorrhage has occurred. These tumors enhance

dramatically (Fig. 3-19). Between the calcification, flow voids, andhemorrhage, the tumor has a heterogeneous appearance, some-times with a salt-and-pepper appearance from vessel supply.

A B

C D

FIGURE 3-19. Choroid plexus papilloma. This choroid plexus mass has a lot of peripheral high signal on T2-weighted image (T2WI) ( A ) and FLAIR(B), signifying edema of the parenchyma. C, Note the hydrocephalus and central necrosis of the tumor, as well as an extraventricular cyst (C) on theenhanced T1WI. D, A mulberry-like shape to the mass, centered on the trigone, is typical of choroid plexus papillomas and carcinomas.





Choroid Plexus CarcinomasChoroid plexus carcinomas (WHO grade III) are much less com-mon than papillomas, with malignant change occurring in fewerthan 10% to 20% of cases. They are usually seen in the lateralventricles. CSF dissemination is the rule with choroid plexus car-cinomas, occurring in more than 60% of cases, but even benignpapillomas may seed the CSF. It is difficult to distinguish abenign papilloma from a malignant one. Parenchymal invasionmay suggest carcinoma. One can have primary melanomas of the

choroid plexus as well.The 5-year survival for completely resected choroid plexus

papillomas is 100%; for carcinomas it is more like 40%.

Choroid Plexus HemangiomasChoroid plexus hemangiomas are benign neoplasms of the chor-oid plexus usually seen in the lateral ventricle. Although thetumor enhances markedly and may calcify, it is usually seen as anincidental finding in an asymptomatic patient. There is an asso-ciation with Sturge-Weber syndrome. In this syndrome, choroidplexus hemangiomas ipsilateral to the leptomeningeal vascularmalformation may be present (see Chapter 9).

Choroid Plexus XanthogranulomaAnother benign condition of the choroid plexus is the xan-

thogranuloma. This incidental lesion may have fat density/inten-sity within it and is also centered on the glomus of the trigone.Curiously, they are frequently bright on DWI scans (Fig. 3-20).They are of no clinical impact, only rarely causing visual distur-bance. Box 3-3 lists common choroid plexus neoplasms. For chor-oid plexus inflammatory processes, consider Box 6-10.

Nonneoplastic Masses

EpidermoidsThere is some confusion involved with putting epidermoids anddermoids into a “tumor” chapter because most people think of theselesions as congenital epidermal inclusion cysts and dermal inclusioncysts. They really are not truly neoplastic and merely reflect twoentities of ectodermal origin, one with just desquamated skin (epi-dermoid) and one with skin appendages such as hair follicles andsebaceous cysts (dermoid). Epidermoids and dermoids grow slowly

and are histologically benign. Teratomas, usually lumped in thesame category, are true neoplasms of multipotential germ cells, however. So despite their variable origins, we have placed these lesionin the neoplasm chapter to be consistent with other authors.

Epidermoids are collections of epithelium with desquamateddebris (keratin and cholesterin) resulting from inclusion of ectodermal rests at the time of neural tube closure early in embryonicdevelopment. The walls are lined by simple stratified squamousepithelium, and the lesion has a pearly appearance. Men andwomen are affected equally, with a peak incidence in the 20- to40-year age range. Epidermoids often occur in the cerebellopontine

angle cistern (where they may present with trigeminal neuralgia andfacial paralysis), the suprasellar cistern, the prepontine cistern, othe pineal region (Fig. 3-21). Extradural epidermoids are nine timeless common than intradural ones and can arise within the diploicspace, the petrous bone, and the temporal bone, where they appeaas well-defined bony lesions with sclerotic borders (Fig. 3-22).

Epidermoids are typically of low density on CT. This is to be distinguished from dermoids or teratomas, which may have fat, bonecalcification, or other dermal appendages associated with themEpidermoids expand to fill the interstices of the CSF space. Anepidermoid is a lesion that is quite aggressive in insinuating itselfaround normal brain structures and often has scalloped bordersCT demonstrates a nonenhancing lobulated lesion. Sometimeepidermoids are hard to distinguish from arachnoid cysts, particularly in the cerebellopontine angle cistern (Table 3-4). Classicallyepidermoids do not enhance. A stereotypical appearance on CT ithat of displacement of the brain stem posteriorly by what appear

B OX 3-3. Choroid Plexus Neoplasms

MeningiomaMetastasesEpendymomaMedulloblastomaChoroid plexus papillomaHemangioma (Sturge-Weber)LymphomaChoroid plexus carcinoma

A B

FIGURE 3-20. Xanthogranulomas of the choroid plexus. Although the FLAIR scan ( A ) may be relatively unremarkable, the diffusion-weighted image(DWI) (B) shows the bright signal in the xanthogranulomas of the choroid plexus (arrows). The presence of protein, cholesterol, or other compounds habeen cited for why these are bright on DWI.





CA B

D

FIGURE 3-21. Epidermoid. A, Sagittal T1-weighted (T1WI) scan without contrast demonstrates a lowintensity mass (E) similar to cerebrospinal fluid (CSF) anterior to the brain stem. Note the scallopedmargin to the lesion at the pons–medulla–cervicomedullary region. B, On the T2-weighted scan, thelesion again has signal intensity similar to CSF. Note Meckel’s cave enlargement ( funky arrow)—is itinvolved or merely dilated? C, No enhancement (no arrow) is seen on the postgadolinium T1WI. D, Aha! The diffusion-weighted scan shows that there is restricted diffusion within the mass and it is dis-similar to CSF based on its very high signal intensity. (Compare with CSF in fourth ventricle.) This isclassic for an epidermoid.

FIGURE 3-22. Extradural epidermoids. Axial computed tomography scanshows a bony lesion scalloping the outer table of the skull (arrows) with asmall superficial soft-tissue mass.

TABLE 3-4. Differentiation of Epidermoid and Arachnoid Cyst

Characteristic Arachnoid Cyst Epidermoid

CT density CSF Slightly higher thanCSF

Margins Smooth Scalloped

Calcification No 25%

Blood vesselinvolvement

Deviates Insinuates betweenvessels

Intrathecal contrast May take up but canbe delayed

No uptake, definesborders

Characteristic onMR sequencesensitive to CSFpulsation(steady-state freeprecession)

Pulsates Does not pulsate

Diffusion Dark Bright

ADC Increased Decreased

FLAIR Dark Bright

ADC, apparent diffusion coefficient; CSF, cerebrospinal fluid; CT, computed tomo-graphy; FLAIR, fluid-attenuated inversion recovery; MR, magnetic resonance.





to be just a dilated cistern anteriorly (see Fig. 3-21). In fact, thiscistern is really a CSF density epidermoid with mass effect.

Magnetic resonance has been very helpful in distinguishingbetween epidermoids and arachnoid cysts, a distinction that issometimes blurred on CT. On MR these lesions are hypointenseon T1WI and hyperintense on T2WI, similar to CSF. The adventof FLAIR imaging has made this an easy diagnosis because epi-dermoids are bright on FLAIR, whereas arachnoid cysts are asdark as CSF. On DWI these lesions are usually very bright and

easily distinguishable from arachnoid cysts, which are dark onDWI. Once again, the lesion does not demonstrate enhancemenunless it has been previously operated or secondarily infectedRarely, epidermoids may be bright on T1WI—this usually is dueto high protein and viscosity in the lesion.

Dermoid The high intensity of fat and signal void of calcification on T1Wsuggests a diagnosis of a dermoid or teratoma (Fig. 3-23). Derma

A

B

D

C

E

FIGURE 3-23. The many faces of der-moids. A, This fatty mass seen on com-puted tomography scan could representa meningioma with fatty degeneration, ateratoma, or a dermoid. It is extra-axial inlocation and scallops bone (arrowheads). B, T1-weighted scan (T1WI) of a differentruptured dermoid shows high signal inten-sity along the superior surface of the cere-bellum (arrows). C, Fat-suppressed T1WIconfirms that lesion is fatty. D, A largermass is seen in the Meckel’s cave regionanteriorly (asterisk). Chemical shift artifact(arrows) is seen along the inferior margin

of the fat droplets extending posteriorly.E, This T2-weighted fat-suppressed scandemonstrates the dark signal suppressedfat ( star ) in the left Meckel’s cave regionas well as dark signal intensity large (black arrows) and small (white arrows) fat depositsalong the cerebellar folia, representing rup-ture of this dermoid tumor.





appendages, such as hair follicles, sebaceous glands, and sweatglands, are found histologically in dermoid cysts. These lesionsmore typically occur in the midline as opposed to epidermoids,which are generally off the midline. Male patients are more com-monly affected, and patients are younger than those with epider-moids. The presence of fat may be suggested by an MR chemicalshift artifact seen as a hyperintense and hypointense rim at theborders of the lesion in the frequency-encoding direction. Fatsuppression scans decrease the intensity on T1WI (see Fig.

3-23C). The possibility of a ruptured dermoid should be consid-ered when multiple fat particles are seen scattered on an MR orwhen lipid is detected in the CSF. (Rule out Pantopaque drop-lets.) Usually the lesions are very well defined.

TeratomaTeratomas are congenital neoplasms seen in neonates containingectodermal (skin, brain), mesodermal (cartilage, bone, fat, muscle),and endodermal (cysts with aerodigestive mucosa) elements.

The pineal and suprasellar regions are common sites for intra-cranial teratomas. One will see a lesion of mixed density andintensity. The presence of an enhancing nodule in this neo-plasm may help distinguish it from a dermoid. Infected or post-operative dermoids and epidermoids may show some peripheralenhancement, however. Teratomas are also common sacral neo-

natal masses.

LipomaLipomas also probably should not be placed in a chapter on neo-plasms because they are most frequently developmental or con-genital abnormalities associated with abnormal development ofthe meninx primitiva, a derivative of the neural crest. Lipomasare particularly common in association with agenesis of the cor-pus callosum, and 60% are associated with some type of congen-ital anomaly of the associated neural elements (see Fig. 9-19).The most common intracranial sites for lipomas are the perical-losal region, the quadrigeminal plate cistern, the suprasellar cis-tern, and the cerebellopontine angle cistern. Because the tissueis histologically normal but located in an abnormal site, lipomasshould best be termed choristomas, not neoplasms. Fat definesthe lipoma; look for low density on CT, high intensity on T1WI,and low intensity on conventional T2WI that suppresses evenfurther when fat suppression techniques are applied.

INTRA-AXIAL TUMORS

The category of gliomas of the brain includes astrocytomas, glio-blastoma multiforme (GBM), oligodendrogliomas, ependymomas,subependymomas, medulloblastomas, neuroblastomas, ganglio-cytomas, and gangliogliomas. Do not lump all tumors under theumbrella of “glioma.” When you mean to, say “astrocytoma.”

Of all intra-axial neoplasms, GBMs account for roughly 25%,astrocytomas 9%, ependymomas 2.5%, medulloblastomas 2.5%,oligodendrogliomas 2.4%, and gangliogliomas 1%. Metastasesaccount for 35% to 40% of intracranial neoplasms.

We follow the WHO classification of brain tumors in our

description of imaging findings in this chapter. We begin withastrocytomas.

Astrocytoma

The grading of astrocytomas by pathology groups is variable, butthe latest WHO classification separates astrocytomas into circum-scribed astrocytomas (grade I), diffuse astrocytomas (grade II),anaplastic astrocytomas (grade III), and GBM (grade IV) on thebasis of histologic criteria (Box 3-4) and gross/imaging appearance.Circumscribed lesions include the pilocytic astrocytomas, sub-ependymal giant cell astrocytomas, and pleomorphic xanthoastrocy-toma (PXA). Fibrillary, gemistocytic, and protoplasmic astrocytomasare classified as diffuse grade II tumors. Then come the nasties—anaplastic astrocytoma and GBM—that are of the highest grade.Syndromes associated with astrocytomas are listed in Box 3-5.

Grade I: Circumscribed Astrocytomas Juvenile Pilocytic Astrocytoma Cerebellar juvenile pilocytic astrocytomas (JPAs) are the mostcommon infratentorial neoplasm in the pediatric age groupand are classified as a WHO grade I astrocytic tumor (Table 3-5). They are seen in children. They are benign. They have

B OX 3-5. Syndromes Associated with Brain Tumors

Basal cell nevus syndrome, or Gorlin syndrome (chromosome9q31)Basal cell nevi and carcinomas, odontogenic keratocysts,

ribbon ribs, phalangeal deformity and pitting, falcinecalcification, craniofacial deformities, scoliosis, andmedulloblastoma

Cowden disease (chromosome 10q23)Multiple hamartomas, mucocutaneous tumors, fibrocystic

breast disease, polyps, thyroid adenoma, Lhermitte-Duclos disease

von Hippel-Lindau disease (see Chapter 9)

Li-Fraumeni syndrome (chromosome 17p13)Increased rate of breast cancers, soft tissue sarcomas,

osteosarcomas, leukemiaAutosomal dominant with astrocytomas, PNET, choroid

plexus tumorsCNS tumors in 13.5%

Maffucci syndromeEnchondromas, soft-tissue cavernomas

Neurofibromatosis types 1 and 2 (see Chapter 9)Ollier syndrome

Multiple enchondromasTuberous sclerosis (see Chapter 9)Turcot syndrome (chromosomes 5q21, 3p21, 7p22)

Colonic familial polyposis, glioblastoma, rare medullo-blastoma

B OX 3-4. Pathologic Criteria for Grading Gliomas

Number of mitosesPresence of necrosisVascular endothelial proliferationNuclear pleomorphismCellular densityGenetic markers (+/-)

TABLE 3-5. WHO Classification of Astrocytic Tumors

Tumor Grade Peak Age (years)

Pilocytic astrocytoma I 0–20

Subependymal giant cellastrocytoma

I 10–20

Pleomorphic xanthoastrocytoma II 10–20

Diffuse astrocytoma II 30–40

Fibrillary II 30–40

Protoplasmic II 30–40

Gemistocytic II 30–40

Anaplastic astrocytoma III 35–50

Glioblastoma IV 50–70

Giant cell glioblastoma IV 40–50

Gliosarcoma IV 50–70





a solid central piece and a separate peripheral portion. In gen-eral, pilocytic astrocytomas are well outlined from normal brain,are usually round, and usually are not ominous in appearance(Fig. 3-24). The lesions, when removed completely, are asso-ciated with an excellent prognosis (5-year survival rate >90%).Sixty percent of pilocytic astrocytomas occur in the posteriorfossa, but they also favor the optic pathways and hypothala-mus. Anaplasia is less common when the tumor is cystic thansolid; therefore, the prognosis varies according to tumor mor-phology. The typical cerebellar astrocytoma in the pediatric agegroup is cystic (60% to 80%), whereas in older patients it is morelikely to be solid. A mural nodule may be present with a similarappearance to the hemangioblastomas of adults. Occasionally

the astrocytomas in the posterior fossa are solid, without a cys-tic component, and may simulate other pediatric posterior fossamasses (Table 3-6).

On MR, astrocytomas show hypointensity on T1WI and hyperintensity on T2WI/FLAIR. The cystic portion of the tumor hasignal intensity similar to CSF on T1WI and T2WI, but maybe hyperintense to CSF on the proton density weighted image(PDWI) or FLAIR because of a larger amount of protein. Thelesion is very well defined. The solid portion of the JPA enhancestrongly. This is a case where a low-grade tumor shows markedenhancement and high metabolic activity on positron emissiontomography (PET) scanning.

Pilocytic astrocytomas also occur in the hypothalamic–opticchiasm–third ventricular region, where they are often associatedwith neurofibromatosis. The astrocytomas in this region ofteninfiltrate the third ventricle and present with hydrocephalus

Diencephalic syndrome characterized by weight loss despitenormal intake, loss of adipose tissue, motor hyperactivityeuphoria, and hyperalertness may occur in cases of chiasmatic

A B

n

C

FIGURE 3-24. Cyst of pilocytic astrocytoma. A, The large cystic mass in the posterior fossa that causes cerebellar tonsillar herniation ( squiggly arrow) andhydrocephalus in this child with a pilocytic astrocytoma.B,C, T2-weighted image shows the dominant feature of the cyst with a small mural nodule (n)

which enhances in C.

TABLE 3-6. Distinctions Among Medulloblastoma, Ependymoma, and Astrocytoma in Posterior Fossa

Feature Medulloblastoma Ependymoma Astrocytoma

Unenhanced CT Hyperdense Isodense Hypodense

Enhancement Moderate Minimal Nodule enhances, cyst doesnot

Calcification Uncommon (10%–21%) Common (40%–50%) Uncommon (<10%)

Origin Vermis Fourth ventricle ependyma Hemispheric

T2WI Intermediate Intermediate Bright

Site Midline Midline Eccentric

Subarachnoid seeding 15%–50% Uncommon Rare

Age (yr) 5–12 2–10 10–20

Cyst formation 10%–20% 15% 60%–80%

Foraminal spread No Yes (Luschka, Magendie) No

Hemorrhage Rare 10% Rare

MRS metaboliteNAA

Lactate Choline

LowAbsentHigh

IntermediateOften presentLess elevated

IntermediateOften presentHigh

CT, computed tomography; MRS, magnetic resonance spectroscopy; NAA, N-acetyl aspartate; T2WI, T2-weighted image.





hypothalamic astrocytomas. Failure to thrive, nystagmus, ele-vated growth hormone levels, and other visual symptoms maycoexist.

Pleomorphic Xanthoastrocytoma These tumors are seen in children and young adults (first threedecades of life). Two thirds occur in patients younger than18 years old. The lesion shows a preference for the periphery of

the temporal lobes as they arise from subpial astrocytes. Theymay show a base at the meninges in more than 70% of cases.Owing to their predilection for the temporal lobes, they causeseizures in most cases. Homogeneous enhancement of the corti-cal mass is common. Cyst formation occurs in about one third toone half of cases, but hemorrhage and calcification are distinctlyuncommon. Margins may be well or poorly defined. Thesetumors may rarely have anaplastic transformation but are con-sidered WHO grade II lesions though circumscribed. Survivalis higher than 80% at 5 years. These tumors are hard to distin-guish from dysembryoplastic neuroepithelial tumors (DNETs)but enhance more frequently. PXAs have a meningeal attach-ment and no cortical dysplasia—these features also help distin-guish them from DNETs.

Subependymal Giant Cell AstrocytomasAnother variant of “glioma” is the subependymal giant cellastrocytoma (SGCA). Classically this lesion is seen in 2- to20-year-old patients with tuberous sclerosis. Patients withtuberous sclerosis may have areas of subependymal nodulesor tubers (which may be calcified on CT), subcortical tubers,and other hamartomatous lesions. SGCAs typically occur nearthe foramina of Monro and, in contradistinction with tubers,demonstrate moderate to marked enhancement (Fig. 3-25; seeFig. 9-50). This tumor may occur in isolation without tuber-ous sclerosis, but it is an uncommon variant. The tumor isslow growing (WHO grade I) and projects into the ventricu-

lar system, where it appears to be a calcified intraventricularmass (Table 3-7). The outflow of the lateral ventricle may beobstructed, leading to trapping of one or both lateral ventri-cles with noncommunicating hydrocephalus. Because manysubependymal nodules show enhancement on MR but not onCT, CT can actually be more specific than MR in distinguish-ing large subependymal nodules from SGCA by virtue of thisfeature.

Grade II: Diffuse Astrocytoma Grade II diffuse astrocytomas are more likely to show absenceof enhancement. They can occur anywhere (Fig. 3-26), but onethird are in the frontal lobes and one third in the temporal lobes.

They are the most common variety to attack the brain stem.Cystic change and calcification may occur (Fig. 3-27).

The fibrillary form of cerebellar astrocytomas is more infil-trative and solid and has a worse prognosis than the pilocyticform. Fortunately, pilocytic astrocytomas constitute 85% ofcerebellar astrocytomas and fibrillary the remaining 15%.Fibrillary astrocytomas occur in older children than do thepilocytic type and are the predominant histologic finding inbrain stem gliomas.

Gemistocytic astrocytomas are found exclusively in thecerebral hemispheres and are a rare variety of supratento-rial gliomas that in 80% of cases ultimately convert to GBMs.Mean survival time is more than 3.5 years, slightly better thananother variety of astrocytoma, the monstrocellular (or magno-cellular) type. The borders are relatively well defined for an

astrocytoma in both these varieties, but no other features aredistinctive.

Brain Stem “Gliomas”Brain stem astrocytomas are usually treated with radiationand do not have as high a survival rate as JPAs. Nonetheless,they are usually WHO grade II diffuse astrocytic tumors witha 25% 10-year survival rate. The masses may be isolated toone part of the brain stem, may grow exophytically (20% ofcases), or may shed cells into the CSF. Pontine and exophyticbrain stem gliomas have a better prognosis than midbrain ormedullary ones, and exophytic ones may benefit from surgicalresection. Typically these astrocytomas are of the diffusefibrillary type, and anaplasia develops in 50% to 60%. Pontine

FIGURE 3-25. Subependymal giant cell astrocytoma. Note the enhanc-ing mass near the foramen of Monro on the right side with a componentof the tumor that extends intraventricularly on this enhanced computedtomography scan. The septum also seems to be infiltrated.

TABLE 3-7. Intraventricular Masses by Site

Neoplasms Lateral Third Fourth

Choroid plexuspapilloma/carcinoma

Common,pediatric

Common,adult

Craniopharyngioma Common fromsuprasellargrowth

Ependymoma CommonMedulloblastoma Common,

growth fromvermis

Meningioma Common,glomus,atrium

Alongchoroidplexus

Metastases Yes Yes Yes

Chordoid glioma Rare Typical Not reported

Giant cellastrocytoma

Common May grow intothird





brain stem gliomas are most common. These masses may beinapparent on CT because of beam-hardening artifact in theposterior fossa, the decreased soft-tissue resolution of CT,and their subtle expansion of the anatomy. By contrast, MRprovides high sensitivity for the lesion and is well suited topreradiation therapy planning with its multiplanar capability.The lesions are high in intensity on T2WI/FLAIR amid thenormal decreased signal intensity of the white matter tracts of

the brain stem (Fig. 3-28). They may (33%) or may not (67%enhance. Cystic degeneration may occur. Subtle enhancementhat cannot be seen with CT may be apparent. Symptomoccur late in the course of the disease because the tumor infiltrates rather than destroys histopathologically. Brain stemastrocytomas also do not produce hydrocephalus until they arefar advanced. As they enlarge they often appear to encircle thebasilar artery.

A B

FIGURE 3-26.Grade II astrocytoma.

A, The mass is somewhat well-defined on FLAIR, but still is pretty bulky.

B, It does not enhance.

A B

FIGURE 3-27. Low-grade astrocytoma. A, T2-weighted scan demonstrates a cystic mass compressing the posterior aspect of the left lateral ventriclewith a small fluid level within it (black arrows). Note the minimal edema (white arrows) present posterior to the lesion. B, After contrast administrationonly a thin rim of enhancement (arrows) is seen with focal nodules anteriorly. Final path: low-grade astrocytoma.





Brain stem astrocytomas may occur in adults; however, 80% ofthe time they are childhood lesions. They comprise 20% of pos-terior fossa masses in children, less common than cerebellar astro-cytomas and medulloblastomas. Other lesions that expand thebrain stem in a child include tuberculosis (most common world-wide), lymphoma, rhombic encephalitis (caused by Listeria), anddemyelinating disorders (acute disseminated encephalomyelitisand multiple sclerosis).

Grade III: Anaplastic AstrocytomaAnaplastic astrocytomas (AAs) occur most commonly in the fourth

and fifth decades of life and usually evolve from lower grade astrocy-tomas. They have ill-defined borders with prolific vasogenic edema.They are much more likely to show contrast enhancement, but ifnecrosis is seen, bump the lesion up to a GBM. When all astrocy-tomas are considered, anaplasia occurs in 75% to 80%, with ultimatededifferentiation into GBM occurring in 50% of cases. Typical timefor progression from AA to GBM is 2 years. Histopathologically,when one finds a GBM there is evidence of a diffuse astrocytomathat may have predated the GBM in 35% of cases.

Grade IV: Glioblastoma MultiformeOf the astrocytomas, GBM (WHO grade IV) is the most commonvariety, nearly twice as frequent as the anaplastic astrocytomasand the grade I astrocytomas and accounting for 50% to 60% ofastrocytic tumors and 15% of intracranial neoplasms. GBM is themost lethal of the gliomas, having a 10% to 15% 2-year survival

rate. These tumors can appear anywhere in the cerebrum butare seen most commonly in the frontal (23%), parietal (24%),and temporal (31%) lobes. The occipital lobes are frequentlyspared.

The majority of GBMs in the elderly are felt to be primarytumors; that is, they do not evolve from lower grade astrocytomas.The clinical course is short—a few months. Secondary GBMs thatarise from dedifferentiation of lower grade astrocytomas occur in ayounger age group and with a more protracted clinical prodrome,over years in duration.

GBM is characterized on imaging by the presence of necro-sis within the tumor. Histologic grade seems roughly to parallelpatients’ age in adults; the older the patient, the more likelythe lesion is to be a higher grade astrocytoma. Other factors that

correlate with higher grade are ring enhancement, enhance-ment in general, marked mass effect, and intratumoral necrosis.Recent reports have found that relative cerebral blood volume(rCBV) correlates well with astrocytoma histology and vascular-ity; the higher the rCBV, the more likely one is dealing with aGBM. At the same time, hemorrhage, as depicted by gradientecho scans, and the presence of lactic acid on MRS have beenlinked to a higher grade. Despite these trends it is not possiblefor the radiologist to supplant the pathologist in grading thetumors.

GBMs infiltrate wildly and are mapped as high signal intensityon long repetition time images. Enhancement may be solid, ring-like, or occasionally inhomogeneously mild (Fig. 3-29). Daughter/

A B

FIGURE 3-28. Brain stem glioma. A, Pontine brain stem glioma on this enhanced computed tomography scan compresses the fourth ventricle (arrows).Note lack of enhancement of the tumor. B, Sagittal T1-weighted image better defines the extent of the tumor on this midline scan.

FIGURE 3-29. Glioblastoma multiforme (GBM). A, This GBM demon-strates irregular enhancement and mass effect with displacement of mid-line structures to the left side.





satellite lesions around the periphery of the mass look like a clusterof grapes on occasion. The tumor frequently crosses the corpus cal-losum, anterior commissure, or posterior commissure to reach thecontralateral hemisphere. Of the adult astrocytomas, GBM is themost common to have intratumoral hemorrhage and subarachnoidseeding (2% to 5% of cases). Occasionally, it coats the ventricles.When you see a lesion involving the corpus callosum (Box 3-6),you should put GBM and lymphoma near the top of the list ofneoplasms (Fig. 3-30). Because of the compact nature of the white

matter fibers in this structure, it is uncommon to have edema spreadacross the corpus callosum. Infarcts involving the corpus callosumare unusual because the blood supply is said to be bilateral throughthe anterior cerebral arteries (now in dispute!). Radiation damagegenerally spares the corpus callosum. The only other lesion of notethat affects the corpus callosum is trauma; there is a propensity forshearing injuries in this location because of its relative fixed loca-tion spanning the interhemispheric fissure.

The extent of a neoplasm is not defined by its enhancing rim.In fact, radiation oncologists treat the entire area of abnormal

B OX 3-6. Corpus Callosum Mass Lesions

NEOPLASMSGBMLymphomaMetastases

WHITE MATTER DISORDERSMultiple sclerosis

Progressive multifocal leukoencephalopathyAdrenoleukodystrophyMarchiafava-Bignami diseasePosterior reversible encephalopathy syndromeEpilepsy–drugs

ACUTE SHEARING INJURIES

STROKE

LIPOMA

A B

C D

FIGURE 3-30. Lesions invading the corpus callosum. A, Glioblastoma multiforme crossing corpus callosum. Enhanced computed tomography scanreveals an irregularly enhancing tumor in a garland wreath pattern (arrows) crossing the splenium of the corpus callosum. Note that the genu of the corpus callosum also shows subtle enhancement denoting tumor infiltration. C marks the splenium of the corpus callosum, which appears to be somewhanecrotic. B, Lymphoma of the splenium. Sagittal T1-weighted scan (T1WI) shows expansion of the splenium with abnormal signal intensity. C, TheT2WI shows a focal mass in the splenium without significant edema. D, The lesion enhances strongly on coronal T1WI. Would this favor lymphomaover an intermediate grade astrocytoma? Try diffusion. (Case courtesy of Stuart Bobman.)





T2WI/FLAIR high intensity with radiation followed by aconed-down portal encompassing the enhancing portion witha 2-cm rim around the enhancing edge. Microscopic infiltrationclearly extends beyond the confines of enhancement, and thehigh signal intensity on T2WI may not represent tumor in allinstances. Neoplastic cells can definitely be present histopatho-logically in brain tissue appearing entirely normal on imagingstudies.

Although the astrocytomas of the posterior fossa in children

are often benign in behavior (JPA), those in the posterior fossa ofthe adult are most commonly anaplastic astrocytomas and GBMs.The GBMs frequently incite a large amount of edema and havetremendous mass effect, often presenting with hydrocephaluscaused by obstruction of the fourth ventricle.

MRS has recently shown that there is a strong relationship withcholine levels in homogeneous nonenhancing astrocytomas andthe Ki-67 labeling index. This in turn corresponds well to gradeof tumor. Ratios of choline and choline-containing compoundsto creatine and phosphocreatine (Cho/Cr) and of Cho to NAA(Cho/NAA) traditionally have been the best predictors of histo-logic grade of tumors, along with the presence of lactate in thehigher grade masses. Most people are using a Cho/NAA ratio ofgreater than 2.2 to denote a high-grade astrocytoma and the pres-ence of myoinositol to suggest lower grade lesions. At the same

time, perfusion imaging parameters have also been shown to beof high value. An elevated CBV of greater than 1.75 is indicativeof higher grade.

Giant cell glioblastomas are WHO grade IV tumors that werepreviously called monstrocellular sarcomas and comprise less than5% of all GBMs. They are glioblastomas that have multinucle-ated giant cells in abundance, TP53 mutations, and a fibrous net-work that causes a more localized appearing tumor. Consider thisa well-demarcated GBM.

Gliosarcoma Consider this a nasty GBM mesenchymal tumor. Gliosarcomasconstitute 2% of all GBMs and favor the supratentorial space.Despite their name they may be well-defined, superficial, andstrongly enhancing.

Multicentric AstrocytomasMulticentric astrocytomas may be due to true metachronous inde-pendent lesions, but more often than not represent contiguousspread of gliomatous tissue, in which the connection is inappar-ent on imaging but present on pathologic study. Multiple inde-pendent glioblastomas occur in 2.3% of GBMs. NF-1 is associatedwith multifocal astrocytomas.

Embryonal TumorsMedulloblastomas/PNET—Grade IV There has been a recent impetus to rename medulloblasto-mas and other similar cell line tumors primitive neuroectodermaltumors (PNETs) (Box 3-7). The rationale is that there really

is no such cell line as the “medullo cell” (at least that is whatthe pathologists tell us). In fact, the latest WHO classificationlists these as embryonal tumors (Table 3-8). In common vernacu-lar, however, the PNET of the posterior fossa is referred to asmedulloblastoma.

Medulloblastomas are one of the most common posteriorfossa masses in the pediatric population, accounting for morethan one third of posterior fossa neoplasms and 50% of cer-ebellar tumors in children. They are quite malignant and haveearned the highest class of aggressiveness (grade IV). Thesetumors are usually seen in the midline arising from the ver-mis and then growing into the inferior or superior velum ofthe fourth ventricle. Medulloblastomas typically occur in the5- to 12-year age range and in boys twice as commonly as girls.Patients usually have hydrocephalus. Brain stem dysfunction

may also be present.As opposed to the pediatric tumors, the 20% of medulloblas-tomas that occur in young adults tend to be eccentric in the pos-terior fossa, residing in the cerebellar hemispheres in more thanhalf the cases. They tend to have a more aggressive course thanthe pediatric tumors and are less well-defined lesions. A rare vari-ety of medulloblastoma known as the desmoplastic medulloblastoma may arise in an extra-axial location, especially in the cerebello-pontine angle.

CT of medulloblastomas typically demonstrate a slightlyhyperdense, well-circumscribed mass before enhancement.The medulloblastoma enhances to a moderate degree in chil-dren and to a lesser degree in adults, possibly because of amore desmoplastic stroma in adults. The homogeneity of den-sity and hyperdensity on CT are the best findings to suggestmedulloblastoma over ependymoma. The mass shows mod-

erate contrast uptake. Medulloblastomas have a 10% to 21%incidence of calcification. Cystic change, initially thought to berare, occurs in 10% to 20% of pediatric cases and 59% to 82%of adult cases (see Table 3-6). The fourth ventricle, when seen,is displaced anteroinferiorly, and obstructive hydrocephalus isoften present.

Sagittal images with MR are optimal for visualizing the ori-gin of the tumors from the vermis. The masses are usuallyhypointense on T1WI and isointense on T2WI. The lesionsare typically very well defined and do not demonstrate a largeamount of edema (Fig. 3-31). A distinguishing feature betweenmedulloblastomas and ependymomas is that the ependymomaclassically enlarges the fourth ventricle while maintaining itsshape, whereas medulloblastomas distort the fourth ventricle.

B OX 3-7. Tumors Classified underEmbryonal PNET Designation

MedulloblastomaMedulloepitheliomaCerebral neuroblastoma/supratentorial PNETEpendymoblastomaPigmented medulloblastoma (melanotic vermian PNET of

infancy)Atypical teratoid/rhabdoid tumor (ATRT)

TABLE 3-8. WHO Classification of Embryonal Tumors


Medulloepithelioma IV 0–5

Ependymoblastoma IV 0–2

Medulloblastoma IV

Desmoplastic IV 0–16, second peakat 21–40

Large cell IV 0–16, peak at7 years

Medullomyoblastoma IV 2.5–10.5

Melanotic IV 0–9

Supratentorial PNET

Neuroblastoma IV 0–10

Ganglioneuroblastoma IV 0–10

Atypical teratoid/ rhabdoid tumor IV 0–5

PNET, primitive neuroectodemal tumor.





On precontrast T1WI calcification and cystic components maydemonstrate either a signal void or CSF intensity, respectively.They enhance.

With medulloblastomas, sugar-coating or nodular subarach-noid space spread may be present. It has been reported to occurin 15% to 50% of medulloblastomas in children. For this rea-

son MR scanning with contrast of the entire spinal axis is rec-ommended to identify subarachnoid seeds. It has been shownthat, for sugar-coating of the cord with tumor, MR is the supe-rior study.

As opposed to some PNETs in adults (cerebral neuroblastoma,adult medulloblastoma), hemorrhage within pediatric medullo-blastomas is relatively uncommon.

The spectroscopic signature of a PNET can distinguish it fromother posterior fossa masses in children. PNETs show low NAA/Cho and Cr/Cho ratios compared with low-grade astrocytomasand ependymomas, which have higher NAA:Cho ratios. The Cr/Cho ratio is highest for ependymomas compared to astrocytomasand PNETs. Lactate is usually not present in PNETs but is oftenseen in pilocytic astrocytomas and ependymomas.

Turcot syndrome (5q21 gene) and nevoid basal cell carcinomasyndrome, or Gorlin syndrome (9q31 gene), are associated witha high rate of medulloblastomas (see Box 3-5). The presence odural calcification in a child younger than age 10 years and a posterior fossa mass should raise the spectre of nevoid basal cell carcinoma syndrome.

Supratentorial PNETCerebral neuroblastomas are now called supratentorial PNETsIf there are ganglion cells present, they may be termed cerebral ganglioneuroblastomas, but either way they are WHO gradeIV, aggressive tumors. The younger the age at diagnosis, theworse the prognosis. These tumors often show cyst formationcalcification (50% to 70%), and hemorrhage and are usually seenin children. They can be seen as hyperdense on unenhanced CTscans. They have a high rate of recurrence and subarachnoidseeding. Usually they are large lesions, 3 to 10 cm in diameterand inhomogeneous in density and intensity; they enhance in aheterogeneous fashion. Occasionally, they arise in a suprasella

A B

C D

FIGURE 3-31. Medulloblastoma.

A, The vermian mass is hyperin-tense on FLAIR and in the mid-line. B, It enhances. C, Seedingby medulloblastoma may be notedby high signal in the subarachnoidspace (arrows) on FLAIR scan-ning, coupled with mild hydro-cephalus. Postgadolinium FLAIRscans can be exquisitely sensitiveto subarachnoid seeding. D, Theimages of the spine confirm suba-rachnoid dissemination in the pos-terior fossa (arrows) as well as onthe thoracic spinal cord and conusmedullaris.





or periventricular location, but cerebral neuroblastomas are mostcommonly found in frontal, parietal, and occipital lobes. Thetumors do not incite much edema and are usually well circum-scribed. Eighty percent arise in patients younger than age 10years (25% before age 2 years), but they can be seen in youngadults. Three-year survival rate is 60%, 5-year is 34%, and recur-rence is common (40%).

Medulloepithelioma Medulloepitheliomas are aggressive grade IV embryonal tumorsthat occur more often supratentorially than infratentorially ininfants. The temporal lobes are affected more often than parietallobes, but this tumor has also been described in the globe. Cysts,calcification, hemorrhage, necrosis, and enhancement occur withtumor progression, which occurs very rapidly. Subarachnoiddissemination occurs in due time.

Ependymoblastoma Another of the WHO grade IV pediatric embryonal tumors,the ependymoblastoma, as opposed to ependymomas, favorsthe supratentorial compartment. The tumors are large atdiscovery, with enhancement, edema, and areas of peripheralnecrosis and cyst formation. Nonetheless, they are relativelywell-circumscribed. They invade the leptomeninges and

usually appose the ventricles, having arisen in periventricularneuroepithelial precursor cells. Death due to CSF disseminationusually occurs within 6 to 12 months of presentation, and presen-tation is in young children and neonates.

Atypical Rhabdoid TumorsRhabdoid tumors are WHO grade IV, highly aggressive, het-erogeneous-looking tumors that may have hemorrhage, necro-sis, calcification, or cyst formation (Fig. 3-32). They are dense

precontrast on CT. They occur in the same time frame asprimitive neuroectodermal tumors (i.e., in the first years of life).Enhancement is patchy. Subarachnoid dissemination is notuncommon (34%), even at presentation, and death is predict-able within 1 year of diagnosis. Fifty-two percent occur in theposterior fossa, 39% are supratentorial, 5% peripineal, and 2%multifocal or intraspinal.

Dysembryoplastic Neuroepithelial Tumor Dysembryoplastic neuroepithelial (neuroectodermal) tumorsare most commonly found in the temporal (50% to 62%) andfrontal (31%) lobes and usually cause seizures. The lesion isa neuroepithelial tumor that looks like a ganglioglioma; mostpresent by the second and third decade of life in patients withchronic seizures. They are located peripherally in the brain,with the cortex involved in nearly all cases and the subcorticalwhite matter in most cases, leading to a wedge-shaped abnor-mality (Fig. 3-33C to E). Half have poorly defined contours.On MR, this tumor is characterized by the presence of cysts,usually multiple. Look for bright, bright T2 signal. The tumoroften has septations and has a triangular pattern of distribution(possibly due to derivation along radial glial fibers). Contrastenhancement is observed in less than a third of the cases (distin-guishing it from a desmoplastic infantile ganglioglioma [DIG]),and mass effect is variable (Fig. 3-33A and B). The lesion isoften hypodense on CT and grows very slowly. The presenceof multiple cysts and the rarity of the lesion in the infraten-torial compartment may help to distinguish a DNET from aganglioglioma (Table 3-9). DNETs usually do not have edemaassociated with them, and they may remodel the calvarium.They are reported to have coincident focal cortical dysplasiaswith them in more than 50% of cases. They rarely recur afterresection, even if partial. WHO grade I.

BA

FIGURE 3-32. Rhabdoid tumor. A, This is a huge, predominantly cystic mass in the left hemisphere. Note, however, that there is solid tissue pos-terolaterally. Check out that mass effect. B, The rim of the mass enhances, and the periphery belies the “grade IV” nature of this aggressive mass.Hydrocephalus is present.





C D

E

BA

FIGURE 3-33. Desmoplastic infantile ganglioglioma (DIG[ A and B] vs DNET [C to E]). A, This large cystic mass (C)in the frontotemporal region has a solid component (arrow)more medially, seen as intermediate signal on the T2-weightedimage (T2WI). B, Typical of a DIG, there is a peripheral solidlyenhancing component to the mass, which has a dural attachment(arrows) and a huge cyst. The differential diagnosis of DIG isDNET, although DIG develops in infants. Do not delete ordefer on DNET. C, DNET. A multicystic mass on precontrastspoiled gradient echo T1WI is seen in the right temporal lobe.

D, The T2WI shows the multifocal abnormality with involve-ment of cortex subcortical regions ( small arrows) and white mat-ter. E, The enhancement is faint and peripheral.





Another location for DNET is the septum pellucidum. A recentreport has described 10 DNETs as nonenhancing, cystic well-defined masses arising from the septum pellucidum and growingintraventricularly in young patients.

Ependymal TumorsEpendymoma Ependymomas are one of a variety of ependymal tumors(Table 3-10) that may occur throughout the brain and spinal cord.

Posterior fossa ependymomas usually are associated with thefourth ventricle, although lesions arising primarily in the foraminaof the fourth ventricle do occur and may present as masses out-side the fourth ventricle (see Table 3-6). Only 20% of ependymo-mas arise intraparenchymally, usually in the supratentorial space.The prognosis with ependymomas varies depending on the site;filum terminale (WHO grade I) is best, followed by spinal cord,followed by supratentorial space, followed by posterior fossa(WHO grade II). There is a 50% 5-year progression-free survivalrate with posterior fossa ependymomas.

Ependymomas have a greater incidence of calcification (40%to 50%) than other posterior fossa pediatric neoplasms. The cal-cification is typically punctate. When cysts are present (15%),

they are small. On unenhanced CT, noncalcified infratentorialependymomas are typically hypodense to isodense without beingcystic. The lesions demonstrate mild enhancement, to a lesserdegree than medulloblastomas. Hydrocephalus is usually presentdue to blockage of the fourth ventricular outflow.

Although ependymomas usually present before age 10, a sec-ond ependymoma peak in the fourth and fifth decades of life isseen. Once again, they often arise as midline lesions that fill thefourth ventricle without displacing it. A classic appearance of a

posterior fossa ependymoma is a calcified fourth ventricular massthat extends through and widens the foramina of Luschka andMagendie. When seen in the cerebral hemispheres, the lesionsare large and are cystic 50% of the time.

On MR the lesions are hypointense on T1WI and tend to beintermediate in intensity on T2WI. Particularly when the lesion isin its infantile form (the ependymoblastoma), it may have signalintensity characteristics that are similar to those of normal braintissue (Fig. 3-34). Hemorrhage is present in approximately 10%of cases. Hypointensities on T2WI may be due to calcification.

Ependymomas are another of the brain tumors that have a highincidence of subarachnoid seeding, and the use of contrast mate-rial is essential to the detection of subarachnoid spread.

Anaplastic EpendymomasAnaplastic ependymomas have an unfavorable prognosis with

more rapid growth rate and more frequent contrast enhancement.The prognosis is worse with younger age, incomplete resection,subarachnoid dissemination, high cell density, and a higher rateof mitoses histopathologically.

Subependymoma Subependymomas are variants of ependymomas that containsubependymal neuroglia. These tumors are WHO grade I andresemble ependymomas in all ways but often do not presentuntil late adulthood. They arise intraventricularly or periven-tricularly and are frequently multiple at autopsy. They mostoften arise in the lateral recesses of the fourth ventricle (50%to 60%) but can be seen in the lateral ventricles (30% to40%) attached to the septum pellucidum (Fig. 3-35). Lateral

TABLE 3-9. Differentiation of Temporal Lobe Lesions

Tumor

Ganglioma

Low-grade Astrocytoma

DNET

Oligodendroglioma

PXA

DesmoplasticInfantileGanglioglioma

Age (years) 0–30 0–30 10–20 30–60 10–35 0–1

Demarcation Well Well Well Less well Well, but malignantchange in 20%

Well

Edema? Very little Yes None Yes Uncommon OccasionallyPercent of

tumors causingtemporal lobeseizures

40% 26% 18% 6% 4% <3%

Hemorrhage Rare Rare Common Variable Rare No

Cyst formation Common Common Common, dominantmultiple

Variable Common Common

Enhancement Uncommon Uncommon Uncommon tovariable

Common Common in muralnodule

Common innoduledesmoplasia

Corticalinvolvement

Common Uncommon Always Variable Common,meningealattachment

Dural attachment

Calcification Variable Variable touncommon

Common Common Rare None

DNET, dysembryoplastic neuroepithelial tumors; PXA, pleomorphic xantheastrocytomas.

TABLE 3-10. WHO Classification of Ependymal Tumors


Cellular II 0–9, second peak 30–50 (spinal)

Papillary II 0–9

Clear cell II 0–9

Tanycytic II 30–50

Anaplasticependymoma

III 0–9

Myxopapillaryependymoma

I 30–40

Subependymoma I 40–60





ventricular subependymomas often arise in patients older thanage 10 to 15 years. The lesion appears isodense on CT, isoin-tense on T1WI, and hyperintense on T2WI, though they maybe heterogeneous lesions. Most (>60%) subependymomas donot enhance, but descriptions of lesions with minimal, mod-erate, and marked enhancement lead to a nonspecific charac-terization. They are infrequently seen in the spinal canal asintramedullary or extramedullary intradural masses. Cyst forma-tion, calcification, and hemorrhage may occur when the tumorsare large; larger tumors occur along the lateral ventricles. Theyhave a benign course with slow growth and a lack of invasive-ness. Surgical resection is curative.

Neuronal, Mixed Neuronal/Glial TumorsGangliogliomasGangliogliomas are most commonly seen in children and youngadults (64% to 80% occur in patients younger than age 30 years)They are the most common mixed glioneural tumors of the CNS(Table 3-11). They are low-grade tumors with good prognoses. Presentation most commonly is with a seizure. The tumorsaffect female more than male patients and are characterized by abenign, slow-growing course often associated with bony remodeling that testifies to their indolent growth. The most commonsites for these tumors are within the temporal lobes (85%), frontalobes, anterior third ventricle, and cerebellum. Gangliogliomas

A CB

FIGURE 3-34. Fourth ventricular ependymoma. A, There is a cystic (c) and solid mass in the fourth ventricle seen on the sagittal T1-weighted image(T1WI). Tumor herniates through the foramen magnum ( squiggly arrow). B, It fills and expands the fourth ventricle and is heterogeneous on T2WI.CNote how it oozes through the foramen of Magendie (arrow) inferiorly to squirt into the cervicomedullary junction. Cystic components (c) are more evi

dent on this enhanced T1WI.

A B

FIGURE 3-35. Supratentorial subependymoma. A, A mass (m) is attached to the septum pellucidum and enlarges the left frontal horn. It is well definedAlthough this was a subependymoma, one should probably include a neurocytoma, low-grade astrocytoma, and ependymoma in the differential diagnosis. B, Different lesion, outer surface of ventricle, enhancing, but the same diagnosis.





of the cerebellum tend to have cystic components but may besolid, mixed, or calcified masses. More than half of them showcontrast enhancement. The grade of the ganglioglioma may bepredicted by fluorodeoxyglucose (FDG) PET or thallium-201

single-photon emission computed tomography (SPECT) activ-ity (usually low uptake). They also frequent the spinal cord andoptic nerves. The lesions are cystic in 38% to 50% of cases andare typically hypodense or isodense on CT. One third show cal-cification and half have faint enhancement (Fig. 3-36). MR fea-tures vary depending on cyst formation. If cysts are present, thenthe ganglioglioma may be hypointense on T1WI and bright onT2WI. A mural nodule may coexist. The tumor is well definedand avascular at angiography. A cystic ganglioglioma can be dis-

tinguished from an arachnoid cyst in that it is clearly intraparen-chymal and has higher signal intensity than CSF or arachnoidcysts on PDWI or FLAIR. Epidermoids may have similar inten-sity properties but are distinguished as being extra-axial.

In children under age 10 years gangliogliomas are larger andmore cystic (83% of cases) than those occurring after age 10 years.More edema may be seen by virtue of the larger size. Solidenhancing components are the rule in both age groups.

The tumor comprises neuronal ganglion cells and astrocyticglial cells, hence its name. However, its behavior is defined bythe degree of dedifferentiation of the glial portion of the tumor;therefore, it may convert into an aggressive lesion, the anaplasticganglioglioma. The presence of vasogenic edema also is corre-lated with worse histologic grade, but most gangliogliomas do notproduce much edema.

TABLE 3-11. WHO Classification of Neuronaland Mixed Neuronal/Glial Tumors


Gangliocytoma I 0–30

Ganglioglioma I or II 0–30

Anaplastic ganglioglioma III 0–30

Desmoplastic infantile

astrocytoma/ganglioglioma

I 0–2

Dysembryoplasticneuroepithelial tumor

I 10–20

Central neurocytoma II 20–30

Cerebellar liponeurocytoma I or II 45–55

Paraganglioma of filumterminale

I 30–70

A B

C D

FIGURE 3-36. Multiple faces of ganglio-glioma. A, Axial unenhanced computedtomography (CT) scan shows a well-defined calcified mass in the superficialportion of the right hemisphere withoutsignificant edema. B, Enhanced coronalT1-weighted image shows a cystic massin the right temporal lobe with a smallperipheral area of rim enhancement(arrows). Gangliogliomas may simulatearachnoid cysts in their appearance andneed not show enhancement. C, Notehow well circumscribed the lesion is,without white matter edema, on the pro-ton density weighted image. D, Anotherganglioglioma demonstrates low densityon CT.





Gangliocytoma As opposed to gangliogliomas, which may undergo malignantdegeneration and a more aggressive growth pattern, ganglio-cytomas have no glial component and no potential for malig-nant change. Gangliocytomas are usually located in the cerebralcortex or the cerebellum. In the cerebellum, some people callthese tumors Lhermitte-Duclos disease, but others believe thisentity is a dysplasia rather than a neoplasia. They may be hyper-dense on noncontrast CT and show little to no enhancement.

Gangliocytomas are often isointense on T1WI and T2WI and arebest seen by their hyperintensity on FLAIR.

Desmoplastic Infantile Ganglioglioma This is a variant of the ganglioglioma that is usually seen in thefirst 2 years of life. The tumors typically occur in the frontaland parietal lobes and have a meningeal base. Cyst formation isthe rule, and peripheral rim or nodular enhancement usually ispresent as well. Some may show a calcified rim. Although thislesion may look like a huge necrotic GBM in an infant, it hasa good prognosis with benign histology (WHO grade I). Thetumor has both glial and ganglionic derivation (no wonder theycall it ganglioglioma). The desmoplasia accounts for the rimof low signal intensity tissue on T2-weighted scans. The dif-

ferential diagnosis will include DNETs and PNETs, but theincidence of calcification and hemorrhage is higher in corticalPNETs (see Fig. 3-33).

Desmoplastic Infantile Astrocytoma(Desmoplastic Cerebral Astrocytoma of Infancy)This probably represents a variant of DIG and is a tumor thathas features of glial and mesenchymal histology. Absence of neu-ronal components histologically distinguishes this tumor from aDIG. It is a benign form of astrocytoma found in early life. Ingeneral, there is a dural-based mass with cystic change. Althoughthe dural-based mass will enhance, the cyst does not, not evenon the periphery. Mass effect and vasogenic edema are rare. Italso presents in the first 18 months of life and is usually seen

supratentorially.

Central Neurocytoma Many of the neoplasms previously called intraventricular oli-

godendrogliomas may actually be neurocytomas (WHO gradeII tumor of neuronal origin) (see Table 3-11). Both calcify fre-quently, may be cystic, and favor the lateral or third ventricle(often with an attachment to the septum pellucidum) (Fig. 3-37).Edema is rare. Central neurocytomas peak in the third decadeof life, mean age 29 years. They are isointense to gray matteron all MR pulse sequences and show mild to moderate enhance-ment with prominent vascular flow voids. Intraventricular neuro-cytomas hemorrhage more frequently than oligodendrogliomas,which may suggest that diagnosis. Usually, however, the radi-

ologist cannot differentiate the two. Electron microscopy andimmunohistochemical markers for synaptophysin can distinguishintraventricular oligodendrogliomas from neurocytomas. Thepathologic distinction is not moot; neurocytomas have a morebenign course than oligodendrogliomas and may not require radi-ation therapy. Oligodendrogliomas show a predilection for theseptum pellucidum as well. The analogy here would be thosecandy dots that are attached to paper, like the mass attached tothe septum pellucidum.

Extraventricular neurocytomas have recently been reported,predominantly in the deep white matter or hemospheric graymatter as large circumscribed heterogeneous masses thatenhance variably. They are often cystic, hemorrhagic, andcalcified.

Oligodendroglial TumorsOligodendroglioma Oligodendrogliomas comprise less than 4% of intracraniagliomas but are typified by their high rate of calcification (40%to 80%) (Fig. 3-38). Peak age range is in the fifth and sixthdecade, and the tumor favors men by a 2:1 margin (Table 3-12)The tumor, when pure, has a benign course (classified as WHOgrade II).

FIGURE 3-37. Central neurocytoma. Axial enhanced computed tomography portrays a calcified mass in the frontal horn of the left latera

ventricle. There is septal infiltration (arrows), typical of an intraventricular neurocytoma. On the basis of a preliminary frozen section thismass had been called an oligodendroglioma. Special stains confirmedneurocytoma (see text). But it can look like a subependymal giant celastrocytoma.

FIGURE 3-38. Calcification in an oligodendroglioma. Although unenhanced computed tomography may seem anachronistic at times for theevaluation of a patient with a brain tumor, this lesion shows typical calcification in this low-grade tumor. The serpentine nature of the calcification should raise the suspicion of an arteriovenous malformation oeven Sturge-Weber, so you still have to get the magnetic resonance scananyway.





Oligodendrogliomas may have calcification (bones), soft tissue(meat), and cystic areas. They appear differently depending onthe contribution of the astrocytic or spongioblastic component.

Juxtaposition of patterns may be seen.Enhancement, when present in oligodendrogliomas, is variable

(present in 50% to 67%). Hemorrhage occurs in 20% of cases, asdoes cyst formation. When the tumor encysts, it has a higher rateof malignant astrocytic behavior. On MR, the tumor is hypoin-tense on T1WI and hyperintense on T2WI/FLAIR except inthe areas of calcification (Fig. 3-39). Heterogeneity of signal isthe watchword. On CT the lesions are hypodense or isodenseon unenhanced scans (unless hemorrhage or calcification is pres-ent) and the skull may be eroded. Edema associated with themass is typically absent, a distinguishing point from other, moreaggressive tumors. Subarachnoid seeding has been reported witholigodendrogliomas.

Mixed TumorsOligodendrogliomas are often histologically mixed (50%) withastrocytic forms; when present, these act as medium-grade neo-plasms with a high rate of recurrence. The term used for this tumoris oligoastrocytoma; like the oligodendrogliomas and anaplastic oli-gos, it populates the frontal and temporal lobes. Calcification

in oligoastrocytomas occurs less frequently (14%) but enhancesmore frequently (50%). Median survival for same grade oligoas-trocytomas is 6.3 years as opposed to 9.8 years for oligodendro-gliomas. If anaplasia occurs with oligoastrocytomas, the mediansurvival drops to 2.8 years.

Anaplastic Oligodendroglioma Anaplastic oligodendrogliomas have a worse prognosis than

WHO grade II oligodendrogliomas. They account for one fourthto one half of all oligodendrogliomas with a mean age of 49 years.More than 90% are found in either the frontal or temporal lobe.Hemorrhage, necrosis, calcification, cystic degeneration, and avidenhancement alone or in combination may occur. Five-year sur-vival is approximately 30%.

Neuroepithelial Tumors of Uncertain OriginGliomatosis CerebriGliomatosis cerebri is a pattern of disease in which at least twolobes of the cerebral hemisphere (especially the cortex) maybe diffusely infiltrated with tumor with a relative lack of masseffect and distortion (i.e., preservation of neuronal architec-ture) (Fig. 3-40). Peak age is 40 to 50 years, but they occur inall adult age groups. WHO classification is grade III, analogousto AA. It is not uncommon to have the frontal and temporallobes involved with the basal ganglia and thalami. Gliomatosiscerebri is bilateral in nearly half the cases. Brain stem involve-ment is not unusual, with the midbrain and pons beingaffected four times more commonly than the medulla. TheWHO classification places the lesion as a subgroup of neuro-epithelial tumors of undefined origin along with astroblasto-mas and chordoid gliomas of the third ventricle. Greenfield’stextbook of neuropathology still calls these tumors of “pleo-morphic glial cell” origin manifested by “more than one typeof glial cell lineage.”

A CT scan may be interpreted as normal in appearance, butyou may see loss of the gray-white differentiation and subtlemass effect. The more sensitive T2WI shows diffuse increased


TABLE 3-12. WHO Classification of OligodendroglialTumors and Mixed Gliomas


Oligodendroglial Tumors

Oligodendroglioma II 30–55

Anaplastic oligodendroglioma III 45–60

Mixed Glioma

Oligoastrocytoma II 35–45

Anaplastic oligoastrocytoma III 40–50

A B

FIGURE 3-39. Calcified oligodendroglioma. A, Axial unenhanced computed tomography (CT) scan demonstrates a calcified mass (arrows) in the rightfrontal lobe with considerable mass effect on the ventricular system. Calcification in the tumor extends across midline just posterior to the falx. B, Highsignal intensity tumor without evidence of the calcification that was easily seen on the CT scan is present on T2-weighted image. One small hypointensefocus (arrow) on the posterolateral aspect may result from the calcification.





signal intensity throughout. Both gray and white matter may beinvolved, and the lesion may spread bilaterally. Enhancement,if present at all, is minimal. The prognosis is equivalent tothat of a high-grade glioma and, in fact, gliomatosis cerebrimay show an explosive growth rate, signifying its transforma-tion to a GBM. Survival is reported to be 48% at 1 year, 27%

at 3 years.

Chordoid Glioma These are tumors of the hypothalamus and anterior third ventri-cle, described in 1998 and assigned WHO grade II, a glial tumorof unknown origin. The lesion is slow-growing, solid, well-cir-cumscribed, and avidly enhancing. They look like little olives sit-ting at the third ventricle—ovoid, sharply delineated. They arehyperdense to gray matter on CT and reasonably isointense onstandard T1WI and T2WI, but may have central necrosis or cys-tic regions. They occur in adults over age 30 and can cause acutehydrocephalus due to their obstructive nature. They may attachto the hypothalamus and have a propensity to regrow if not totallyremoved.

Astroblastoma Astroblastomas are rare tumors of variable aggressiveness and ounknown origin. They are tumors of young adulthood affecting thecerebral hemispheres. They are well-circumscribed tumors withperipheral enhancement, central necrosis, and are usually largePrognosis is good as long as the surgeon does a complete resection

HemangioblastomasThe most common primary intraparenchymal tumor in theinfratentorial space in adults is a cerebellar hemangioblastoma(HB). This is a benign tumor, WHO grade I, readily curable withsurgery. More than 83% of HBs occur in the cerebellum; theremainder are split among the spinal cord, medulla, and cerebrumin a 4:2:1 ratio. Approximately 10% of posterior fossa masses areHBs. They are far outnumbered by vestibular schwannomas andmetastases. Men are more commonly affected than women, andthe patients are usually young adults. The common symptomare headache, ataxia, nausea, vomiting, and vertigo. Polycythemiacaused by increased erythropoietin production may be a clinicafinding in 40% of cases and is more common with solid HBs

A

B C

FIGURE 3-40. Gliomatosis cerebri. A, Lesion is clearly seen on

the T2-weighted image. Note the high signal intensity throughoutthe right temporal lobe not respecting the gray-white boundaries.B, This case of gliomatosis cerebri illustrates how the lesion hasbecome less difficult to define now that magnetic resonance domi-nates the realm of central nervous system imaging. The FLAIRsequence has taken the mystery out of the mass. You can see thediffuse infiltration of the cortex of the left temporal and occipitallobes (arrows) on this case. C, Close up.





A spinal HB may present with subarachnoid hemorrhage. Twenty-five percent of HBs occur in association with von Hippel-Lindaudisease (VHL).

The stereotypical findings of an HB are those of a cystic masswith a solid mural nodule (55% to 60% of cases), which is highly vas-cular and has serpentine signal voids of feeding vessels (Fig. 3-41).(Think of a red strawberry amid whipped cream.) However, solidHBs (40%) and, less commonly, purely cystic HBs occur as well. Youwill see a cystic mass in the hemisphere or vermis of the cerebellum

with a slightly hyperdense mural nodule on the unenhanced CTscan. The mural nodule demonstrates striking enhancement. Thecyst and its walls do not enhance. A purely solid HB also demon-strates strong enhancement (Fig. 3-42).

On angiographic examination a vascular nodule amid an avas-cular mass, usually with serpentine vessels, may be identifiedwith or without draining veins. Because sometimes the differen-tial diagnosis includes a meningioma of the tentorium, absence ofdural vascular supply strongly mitigates against the diagnosis ofa tentorial meningioma. In addition, because the multiple HBsassociated with VHL may be very small, the angiogram may helpas a screen for lesions. VHL has been mapped to a gene on thethird chromosome (3p25-26).

The MR scan demonstrates findings similar to those of the CTscan, with varying components of cystic and solid tissue. However,

the advantage of MR is in showing the large vessels feeding themural nodule of the HB and the presence of any subtle hemor-rhage that may have occurred. The tumors usually reach the pialsurface of the brain and therefore may simulate the appearanceof a meningioma. The mural nodules of HBs may be multiplein a single lesion rather than multiple HBs. Treatment requiresremoval of the solid nodule of the lesion only, because the cyst isnot really neoplastic. Prognosis is very good, with a 5-year survivalrate of more than 85%.

Because this description is nearly the same as that for JPAs, youmay ask how to distinguish the two. First and foremost is age: JPAsare seen in the age range 5 to 15 years versus age 30 to 40 years forHBs. Given a 23-year-old with a cystic solid mass, go with five find-ings: (1) a pial attachment would suggest HB; (2) a tiny nodule with ahuge cyst is more likely HB; (3) (if pushed) an arteriogram will showthe nodule to be hypervascular with HB and hypovascular with JPA;(4) multiplicity and association with other findings of VHL suggestsHB; and (5) coincidental and retinal HB favors VHL.

Hemangioblastomas associated with VHL (Box 3-8) generallypresent at an earlier age. VHL syndrome is inherited as an auto-somal dominant trait, with nearly 90% penetrance. HBs associ-ated with VHL may be multiple in the cerebellum, brain stem,and spinal cord. Current criteria for establishing the diagnosis ofVHL are (1) more than one CNS (including retinal) HB, (2) oneCNS HB and one visceral lesion (e.g., renal angiomyolipoma,renal cell carcinoma), or (3) one manifestation of VHL and a posi-tive family history. One difficulty in analyzing patients with VHLoccurs when the patient has a known renal cell carcinoma or meta-static pheochromocytoma. Often it is impossible to distinguishhypervascular metastases (which may be single or multiple) fromHBs (which also may be single or multiple).

When reviewing images of the posterior fossa in a patient withVHL, don’t forget to peruse the temporal bone for endolymphaticsac tumors, which arise in 11% to 16% of patients with VHL andmay be bilateral in 33%.

A

B

C

FIGURE 3-41. Hemangioblastoma (HB) ofthe cerebellum. A, Note the HB with botha cyst and a mural nodule (arrowheads) onthis unenhanced axial T1-weighted image

(T1WI). B, Postcontrast T1WI demonstratesan enhancing solid HB with small flow voidsalong its circumference in a different patient.C, Vertebral artery angiogram shows tumorstain (arrows) in another cerebellar HB withvascular supply from the posterior inferiorcerebellar artery and branches of the superiorcerebellar artery.

FIGURE 3-42. Multiple hemangioblastomas. Peripheral nodules ofenhancement are seen on this enhanced coronal T1-weighted image in thispatient with multiple hemangioblastomas and von Hippel-Lindau disease.





MetastasesThe most common infratentorial neoplasm to occur in the adulpopulation is a metastasis (Fig. 3-43).They are usually seen awell-defined, round masses that are identified near the gray-white

junction (Fig. 3-44). These lesions show contrast enhancemenand are one of the lesions of the brain that can cause nodularor ring enhancement. The most common primary extracraniatumors in adults to metastasize to the infratentorial part of thebrain are lung and breast carcinomas. Bronchogenic carcinomas

spread to the CNS in 30% of cases, although squamous carcinomais the least frequent subtype to metastasize to the brain. It is estimated that CNS metastases develop in 18% to 30% of patientswith breast cancer. Other neoplasms that have a propensity formetastatic spread to the brain include melanoma (third moscommon, after lung and breast), renal cell carcinoma, and thyroidcarcinoma. Virtually all metastases evoke some vasogenic edemahowever, the amount is variable.

Unless the metastatic deposit is hemorrhagic, calcified, hyperproteinaceous, or highly cellular, where it would be hyperdense onnoncontrast CT, most metastases are low density on unenhancedCT. Rarely, one may identify calcification in metastatic deposits (Box 3-9). Metastatic deposits may have variable intensity

B OX 3-8. Lesions Associated with VHL Disease

CNSCerebellar HB (66%–80%)Spinal HB (28%–40%)Medullary HB (14%–20%)Extra-axial HB (<5%)Retinal HB (50%–67%)

RENALCysts (50%–75%)Hypernephroma (25%–50%)HemangioblastomaAdenoma

PANCREATICCysts (30%)AdenomaAdenocarcinomaIslet cell tumor

LIVER HemangiomaCystAdenoma

SPLEEN Angioma

ADRENALPheochromocytoma (10%)Cyst

LUNGCyst

BONEHemangiomaEndolymphatic sac tumor (<10%)

CARDIACRhabdomyoma

EPIDIDYMISCystCystadenoma

POLYCYTHEMIA (25%–40%)

B CA

FIGURE 3-43. Multiple posterior fossa metastases. A, T2-weighted examination shows very (±) subtle high signal intensity in the posterior right cer-ebellum and in the right nodulus. B, With contrast enhancement, the ring enhancing metastasis (arrow) is well seen. C, Additional metastases are seenin the superior vermis of the cerebellum (arrow) and in the occipital lobes (arrowheads) at the gray-white junction.

FIGURE 3-44. Large metastasis. The gray-white junction is the classiclocation for a metastasis. A large amount of edema for the size of the masis another salient feature.





on T2WI. Some lesions are isointense to gray matter on T2WIand can be readily distinguished from the high intensity of theedema they elicit. Other metastatic deposits, however, are hyper-intense to gray matter on T2WI. Occasionally one may identifysignal intensity characteristics that suggest a primary diagnosis.Hemorrhagic metastases are usually seen as areas of high signalintensity on T1WI and T2WI with a relative absence of hemosid-erin deposition (Box 3-10).

Hemorrhagic metastases must be differentiated from occultcerebrovascular malformations or nonneoplastic hematomas(Table 3-13; Fig. 3-45). Some primary neoplasms, such as mela-noma, renal cell, choriocarcinoma, and thyroid carcinoma, have aparticular propensity to hemorrhage, be it at the primary site orwithin metastases. However, because lung and breast cancers areso much more common than these primary tumors, a hemorrhagicmetastasis is most often from breast or lung. With a single hemor-rhagic lesion, primary brain tumors, such as GBM and oligoden-droglioma, should be considered along with a solitary hemorrhagicmetastasis.

In the case of melanoma one can identify nonhemorrhagic mel-anotic metastases as lesions that have high intensity on T1WI andisointensity to hypointensity on T2WI caused by intrinsic para-magnetic effects. Although some investigators believe that theparamagnetic effect is due to paramagnetic cations, others believeit to be due to free radicals and still others feel this is an inher-ent characteristic of melanin. However, an amelanotic melanoma(without melanin) without hemorrhage may have signal intensity

characteristics similar to those of other nonhemorrhagic metasta-ses: low signal on T1WI and high signal on T2WI. Furthermore,

hemorrhagic melanoma metastases, be they melanotic or amelan-otic, have signal intensity similar to other hemorrhagic nonmelan-otic lesions. In fact, the real issue may be the percent content ofmelanin in the melanoma metastasis; those containing more than10% melanotic cells demonstrate the typical melanotic MR imag-ing pattern (bright on T1WI, dark on T2WI). If the content isless than 10% melanin-containing cells, a variety of MR imagingpatterns can be present. About half of patients with amelanoticlesions show the characteristic melanotic MR imaging pattern,likely because of hemorrhage.

B OX 3-9. Calcified CNS Tumors

METASTASESMucinous adenocarcinoma

BreastColonLungOvaryStomach

OsteosarcomaChondrosarcoma

PRIMARY CNS TUMORSOligodendrogliomaMeningiomaCraniopharyngiomaPineal region tumors (see Table 3-14)EpendymomaNeurocytomaChoroid plexus papillomaGangliogliomaAstrocytoma

NEOPLASMS POSTRADIOTHERAPY

B OX 3-10. Hemorrhagic Metastases

MelanomaRenal cell carcinomaBreast cancerLung cancerThyroid cancerRetinoblastomaChoriocarcinoma

TABLE 3-13. Features of Recently BledOccult Cerebrovascular Malformationsversus Hemorrhagic Metastases

Feature

HemorrhagicOccultCerebrovascularMalformations(Cavernomas)

HemorrhagicMetastases

Edema Only with acuteepisode, resolvesby 8 wk

Persistent

Mass Variable but resolves Moderate to large,persistent

Hemosiderin ring Complete Incomplete orabsent

Nonhemorrhagic tissue Absent Present

Enhancement Minimal and central Nodular, ring, oreccentric

Progression ofhemorrhagic stages

Orderly Delayed

Follow-up Decreases in sizewith time

Increases in sizewith time

Calcification Approximately 20% Rare

FIGURE 3-45. Hemorrhagic metastases. Hyperdense masses are seen in

the brain stem and cerebellum. Although one might consider cavernomasin the differential diagnosis, this patient had renal cell carcinoma. Theedema around the mass in the cerebellum can be seen.





Metastases are also the most common masses in the supraten-torial space in the adult, making up 40% of intracranial neo-plasms. Fifty percent are solitary and 50% are multiple, with just20% having two lesions. Just as in the infratentorial compart-ment, the primary tumors that spread to the supratentorial partof the brain are lung (50%) (Fig. 3-46), breast (15%), melanoma(11%), kidney, and gastrointestinal primary tumors. Solitarymetastases favor a breast, uterine, or gastrointestinal primarysite, whereas hemorrhagic ones favor kidney, melanoma, thyroid,breast, and choriocarcinoma. Cystic or calcified metastases favorlung, breast, and gastrointestinal primary sites (Fig. 3-47). If theprimary site is not clinically or radiographically apparent, thedifferential diagnosis becomes an astrocytoma. A solitary lesionwarrants thought.

Remember to peruse the calvarium for metastatic disease asyou look at the scans. In the authors’ experience, bony metastasesof the skull occur more frequently than parenchymal metastasesin many primary tumors. This is certainly true for prostatemetastases, where parenchymal metastases without bony diseaseare virtually reportable. Furthermore, a recent study has indicated

that breast primary tumors that are estrogen- and progesteronereceptor positive have a much higher rate of osseous metastasesthan brain ones (and the skeletal ones occur earlier in the courseof the breast cancer). Those who are receptor-negative developbrain and meningeal but not calvarial metastases.

Metastases usually appear as relatively well-defined masses thademonstrate enhancement and moderate edema. They characteristically lodge at the gray-white boundary because of the small caliber of vessels in this region and may extend into the cortex or white

matter. The lesions tend to follow vascular flow dynamics, beingdeposited in the carotid system more commonly than in the vertebrobasilar system (80% to 20%, respectively) and favor the middlecerebral artery distribution. Metastases lodge at the gray-white interface in 80% of cases, basal ganglia in 3%, and cerebellum in 15%.

Metastases are typically hypodense on noncontrast CT andhypointense on T1WI unless hemorrhagic (Fig. 3-48) or hypercellular. Although hypointense (when visible) on unenhanced T1WIthey may be of variable signal intensity on T2WI, depending onthe presence of hemorrhage, intratumoral necrosis, cyst formationhigh nuclear/cytoplasm ratios, or paramagnetic content. Nearly almetastases enhance to a variable degree, but the pattern may besolid, ringlike, regular, irregular, homogeneous, or heterogeneousAs opposed to gliomas, metastases are better defined and havesharper borders. The vasogenic edema is often out of proportion

to the size of the metastasis, except in cortical metastases, whereedema may be minimal or absent. When edema is absent, T2Wmay miss metastases. Contrast becomes essential for identification of lesions in this situation (i.e., cortical metastases).

Because solitary metastases in a noneloquent area of the brain maybe treated surgically, it is very important to demonstrate to clinicianwhether there are one, two, three, or multiple metastases. Recentlysome investigators have shown improved detection and visibility ometastases with the use of triple-dose MR contrast agents. The number of lesions and their conspicuity increased with increasing contrasdosage. The question is: Do the numbers increase faster than the cosof the contrast? Where the maximum limit of contrast dosage will stopno one knows yet. Still others believe that one should delay imagingafter contrast administration by up to 30 minutes to increase lesionconspicuity. 3T or higher scanners may show more mets per mL oGad than 1.5T or lower scanners.

One technique used to increase the conspicuity of metastaseis to apply magnetization transfer suppression to the postcontrast T1-weighted scans. This suppresses more of the high pro-tein background and can make the enhancing meatballs show upbrighter on a darker background. To some, this is a poor man’striple-dose gadolinium study at one third the cost. Some advocate

FIGURE 3-46. Multiple small-cell carcinoma lung metastases. The pre-ponderance of small enhancing lesions (arrowheads) at the gray-white

junction on this sagittal postcontrast scan suggests a diagnosis of meta-

static disease.

A B

FIGURE 3-47. Supratentorial meat-balls. A, Cystic and solid metastasesare present in this patient. The cysticlesion in the left temporal lobe doesnot have the same intensity as cere-brospinal fluid due to high protein.B, The masses enhance along theperiphery, and the posterior righttemporal lesion reveals its nature. Thedifferential diagnosis would include abrain abscess, and a diffusion-weightedscan could be useful if bright (suggest-ing an abscess and differentiating thetwo).





using gadolinium and FLAIR scanning. Because the CSF andbrain tissue is of low intensity with FLAIR scans, tumors appearmore conspicuous than on conventional FLAIR or T2-weightedscans. Either way, it is important to address such issues, especiallywhen dealing with presumed solitary, resectable metastases (toexclude additional metastatic deposits).

The neurosurgeons will remind you that they are ready andwilling to resect some metastases purely because of unresponsivemass effect and impending herniation. Recent studies have sug-gested benefit in resecting (or gamma-knifing) as many as threeseparate well-circumscribed metastases.

Paraneoplastic SyndromesParaneoplastic conditions of the brain may occur in associationwith non-CNS primary tumors. Among these, limbic encepha-litis, an abnormality affecting the temporal lobes and causingmemory and mental status changes, has been described exten-sively. The appearance simulates a herpes simplex encepha-litis, usually bilateral (though it may be unilateral in 40%), andextensive disease in the temporal lobes, which is bright on T2WIand may show enhancement (Fig. 3-49). Atrophy of the tempo-ral lobe may coexist but hemorrhage is exceedingly uncommon.Abnormal signal intensity in the brain stem or hypothalamus may

A B

FIGURE 3-48. Melanoma metastases. A, Enhanced magnetic resonance scan shows many small peripheral masses (arrowheads) in the brain. B, Somewere bright on precontrast T1-weighted image. This was a case of metastatic melanoma where the high signal was due to melanin or hemorrhage.

BA

FIGURE 3-49. Limbic paraneoplastic encephalitis. A, Bilateral mesial temporal lobe hyperintensity is present on the FLAIR scan in this patient withovarian cancer. B, Atrophy argues against acute herpes encephalitis.





be seen in approximately 10% to 20% of cases of limbic encepha-litis. Many different primary tumors have been associated withlimbic encephalitis: small-cell carcinoma of the lung is classic;testicular germ cell, thymic, ovarian, breast, hematologic, andgastrointestinal malignancies have also been reported. The etiol-ogy is not well understood. Another paraneoplastic syndrome isthat of cerebellar atrophy with clinical manifestations of ataxia.Ovarian carcinoma and lymphoma may cause this finding.

The series of antibodies indicating paraneoplastic syndromes

is like a Hip Hop lexicon (anti-Yo, anti-Hu, anti-Ma, anti-Ri,anti-CAR, anti-Ta [also called anti-Ma2]). If you hear these terms,know to look closely at the temporal lobes and cerebellum! Theanti-Hu antibodies are most common in the paraneoplastic formof limbic encephalitis, but anti-Ta and anti-Ma antibodies canalso be seen. Anti-Hu antibodies are directed against the nucleiof neurons and can cause a syndrome of encephalomyelitis orsensory neuropathy. The anti-Hu antibodies are frequently asso-ciated with small-cell lung carcinoma, whereas anti-Ta are seenwith testicular germ cell tumors. The anti-Yo antibody producesa syndrome of cerebellar degeneration secondary to the antibod-ies’ assault on the Purkinje cells of the cerebellum. An associationwith ovarian carcinoma is high. Anti-Ri antibodies cause opso-clonus and ataxia and are seen often with breast and lung can-cers. Finally, the anti-CAR antibodies attack retinal neurons and

cause a retinopathy. They are seen with small-cell carcinomas.Treatment of the primary tumor usually results in improvementof the paraneoplastic syndrome.

Tumors of Hematopoietic OriginLymphomas (Primary CNS Lymphoma [PCNSL])The most common type of lymphoma to affect the brain is diffusehistiocytic lymphoma (also known as reticulum cell sarcoma, micro-

glioma, and primary cerebral lymphoma). CNS lymphoma is oftenassociated with an immunodeficiency state, including those result-ing from acquired immunodeficiency syndrome (AIDS), organtransplantation, Wiskott-Aldrich syndrome, Sjögren syndrome,and prolonged immunosuppressive therapy. I think of lymphomaas the rotten apple of the smorgasbord. You can have scatteredrotten apples seen as multiple masses, rotten apple sauce coatingyour ventricles (Fig. 3-50), rotten apple juice that looks like clearCSF but is infiltrated with tumor cells, or one large rotten applepie occupying much of your brain. Because of the AIDS epidemicin the world, lymphoma is projected in the next decade to becomethe most common primary malignancy of the brain, as it occurs in6% of AIDS patients. Cell phone usage may have something to dowith the rates of brain tumors in the future, however.

It is thought that the dysfunction of suppressor T cells in immu-nosuppressed patients leads to this B-cell lymphocytic neoplasm.Primary CNS lymphoma of the brain (where no other sites are

discovered) is usually supratentorial, although infratentorial primary lymphoma is not rare. Lymphomas tend to be located in deepgray matter nuclei or in the periventricular white matter. Coating othe ventricles (seen in 38% of cases) and spread across the corpuscallosum are features of lymphoma that are suggestive of, althoughnot specific for, the diagnosis. The other diagnosis seen in a similapopulation is toxoplasmosis; however, toxoplasmosis usually doenot abut an ependymal surface as lymphoma does (Table 3-14).

A B C

FIGURE 3-50. Ependymal spread of lymphoma. The combination of low signal (arrows) on FLAIR ( A ) and ependymal enhancement (B and C) shouldsuggest the diagnosis of lymphoma in this case. Encasement of the ventricles and invasion of the septum pellucidum is evident.

TABLE 3-14. Lymphoma versus Toxoplasmosis in AIDS

Feature Lymphoma Toxoplasmosis

Multiple lesions 81% 61%

Size Diameter 1–3 cm in75%, >3 cm in 25%

Diameter <1 cm in52%, 1–3 cm in36%, >3 cm in 12%

Mean number of

lesions

3.9 3.3

Homogeneous CTenhancement

76% if <1 cm, 50% if>1 cm

77% if <1 cm, 23% if>1 cm

Hyperdensity onunenhanced CT

33% of lesions None, unlesshemorrhage

T2WI 55% isointense All hyperintense

Periventriculardistribution

50% of patients 3% of patients

Subependymal 38% None

Radiation therapyeffect

Very sensitive Gornicht helfen(no help)

Basal gangliainvolvement

Uncommon Common

Hemorrhage Rare More common,especially aftertreatment

Thallium-201SPECT scan

Positive Negative

MR perfusion Increase Decrease

MRS Marked increase incholine and lipid,low NAA

Markedly elevatedlactate

Steroids Melts like butter No effect

AIDS, acquired immunodeficiency syndrome; CT, computed tomography; MR, magnetic resonance; MRS, magnetic resonance spectroscopy; NAA, N-acetyl aspartateSPECT, single-photon emission computed tomography; T2WI, T2-weighted image.

From Dina TS: Primary CNS lymphoma versus toxoplasmosis in AIDS, Radiolog179:823-828, 1991.





Recent studies have shown that thallium scanning is an excel-lent means for distinguishing toxoplasmosis from CNS lymphoma.The latter is thallium avid; the former does not show activity withthallium scanning. This is an excellent, though underutilized,means to distinguish these two entities and affect an early courseof therapy directed at the correct diagnosis. Do it! Another sug-gested way to differentiate the two, while sticking with your MRscanner, is to perform perfusion scans. Lymphomas have higherregional CBV compared with surrounding tissue, whereas toxo-

plasmosis is hypovascular. (See Chapter 6.)Secondary lymphoma most commonly involves the leptome-

ninges and CSF (apple juice); but this is rarely detectable on CTor MR, even with enhancement. Hydrocephalus may be the onlytelltale sign. Dural invasion is a rarity. When one has parenchy-mal extension by secondary lymphoma, it is usually supratento-rial and is more commonly multifocal. Dense enhancement is thenorm; however, ring enhancement may also occur. Non-Hodgkinlymphoma is more common than Hodgkin lymphoma, whichrarely affects the brain.

The classic teaching used to be that lymphoma was one ofthe lesions that is typically hyperdense on noncontrast CT andenhances to a moderate degree (Fig. 3-51). Such generalizationsare no longer valid since AIDS-related lymphoma has come intoascendance. Lymphoma in AIDS patients has a variety of appear-

ances, most commonly hyperdensity on noncontrast CT andvariable enhancement. Nonetheless, if you see a hypodense infil-trative mass on a noncontrast CT in an adult positive for humanimmunodeficiency virus, still consider lymphoma. Hemorrhage isdistinctly uncommon in lymphomas (<8%).

Magnetic resonance findings in CNS lymphoma are varied.Periventricular (40%), subcortical and deep gray matter abnor-malities (27%), and mixed patterns (20%) are most common, withmasses less than 2 cm in size in patients with AIDS and greaterthan 2 cm in non-AIDS patients. Non-AIDS PCNSL does notcalcify and is most commonly seen in the frontal lobes and basalganglia; close to 50% abut the ventricular surface from a whitematter origin. Multiple lesions (35% versus 60% to 80%) occurmore commonly in patients with AIDS, making the distinctionwith toxoplasmosis even more difficult. The signal intensity isvariable on T2-weighted scans, with approximately 50% of casesisointense to slightly hypointense. Heterogeneity is the norm.Gadolinium enhancement is marked and homogeneous in morethan 90% of non-AIDS cases, but beware when steroids are givenas treatment because these drugs may suppress the enhance-ment. Ring enhancement is often seen (25%) in immunodeficientpatients but is rarely seen in the immunocompetent population.Because lymphoma and GBM are often partners in the sentencefor differential diagnoses of many malignant-looking brain masses,it is useful to note that the fractional anisotropy (FA) and ADCvalues of lymphoma (0.14 and 0.63, respectively) are significantly

lower than those of GBM (0.23 and 0.96). Using cutoff values of0.192 for FA and 0.82 for ADC, one can achieve accuracies in the95% range.

Lymphomas are said to have low ADC due to their densecellularity restricting water diffusion (Fig. 3-52). Though themass is somewhat bright on DWI, one should not confuse itwith a lightbulb-bright stroke, which is confined to a vasculardistribution. The Cho/Cr ratio is elevated in CNS lymphoma,and CBV is decreased compared to values in high-grade

astrocytomas.Intravascular lymphomatosis (angiotropic/angiocentric B-cell

malignant lymphoma) is a deadly disease that presents with adifferent spectrum of imaging findings than classical parenchy-mal lymphoma. One sees a multifocal process that favors thesupratentorial white matter and is characterized by linear areasof enhancement or restricted diffusion. A tigroid pattern ofT2-weighted signal predominates. The degree of mass effect isdisproportionately less than expected compared to the extent ofT2-weighted signal abnormality. The entity may also be seen inthe spine as cord or nerve root enhancement.

SarcomaThe most common forms of sarcomas in the CNS are found alongthe meninges (meningosarcomas, angiosarcomas, and fibrosarco-mas) and have a propensity to invade the brain. Of the primaryparenchymal sarcomas, gliosarcoma is most common and has fea-tures of both a GBM and a sarcoma. The prognosis cannot getmuch worse than a GBM, but gliosarcomas are said to have ahigher rate of distant metastases. They tend to occur in the tem-poral lobe and often invade dural surfaces.

Pineal Region Masses

The pineal gland grows steadily until age 2 years and then thesize stabilizes into early adulthood. No difference in size existsbetween males and females. The normal pineal gland is calcifiedin 7% to 10% of patients from age 8 to 10 years, 30% of patientsin their midteens, and peaks by age 20 to 40 years at 33% to 40%of individuals. A calcified pineal gland before age 6 years should

be viewed with suspicion for adjacent tumor, and calcified glandsover 1.0 cm in size are also worrisome. African Americans havea lower rate of pineal calcification than Caucasian Americans.Fijians and Indians have the highest rates.

Pineal region masses constitute 1% of all CNS tumors. Theyare generally separated into two categories: those of germ cellorigin (60%) and those of pineal cell origin (Tables 3-15 and 3-16). The manifestations of pineal region masses are basedon their site near many critical structures: the aqueduct, thetectal plate, the midbrain, the vein of Galen. Remember also

A B

FIGURE 3-51. Periventricular lymphoma. Precontrast ( A ) andpostcontrast (B) computed tomography scans demonstrate theclassic findings of lymphoma; a hyperdense mass on an unen-hanced scan (arrows), which shows enhancement after iodinatedcontrast administration and infiltrates the ependymal surface of theventricular system.





A B C

FIGURE 3-52. Low apparent diffusion coefficient (ADC) value in lymphoma. A, Through the bright edema on the FLAIR scan, one can make out alower intensity mass (arrowheads) in the Wernicke area. Abnormal signal crossing the corpus callosum should send off alarm bells. B, The mass enhancedramatically and clearly does not look like a stroke. C, ADC map shows low signal, indicating restricted diffusion in the tumor (arrowheads) and surround

ing high intensity vasogenic edema. Hypercellular/small-cell tumors can show reduced ADC.

TABLE 3-15. Pineal Region Masses: Differential Diagnosis of Germ Cell Tumors

Characteristic Germinoma Choriocarcinoma Teratoma Yolk Sac Tumor

Age/sex Child/M>>F Child/M>F Child/M>F Child/M>F

Density on unenhanced CT Hyperdense Variable (hemorrhagepredilection)

Variable (fat, calcification,teeth)

Hypodense

Calcification Accelerates pinealcalcification

Rare Frequent Absent

Enhancement Marked Moderate Minimal Rare

Heterogeneity Homogeneous Heterogeneous Heterogeneous Heterogeneous

Subarachnoid seeding Frequent Infrequent Infrequent Rare

Serum markers Placental alkalinephosphatase,sometimes HCG

HCG, human placentallactogen

HCG and alpha-fetoprotein Alpha-fetoprotein

Hemorrhage Yes Yes, yes Possible No

Other Boys, boys, boys Hemorrhage is the word Variable density and intensity,third molar

CT, computed tomography; HCG, human chorionic gonadotropin.

TABLE 3-16. Pineal Region Masses: Differential Diagnosis of Non–Germ Cell Tumors

Characteristic Pineoblastoma Pineocytoma Astrocytoma

Age/sex Child/M = F Child or adult/M = F Child or adult/M = F

Density on unenhanced CT Hyperdense Hyperdense Isodense

Calcification Engulfs pineal Engulfs pineal Absent

Enhancement Moderate Moderate Variable

Heterogeneity Homogeneous Homogeneous Homogeneous

Subarachnoid seeding Frequent Infrequent Infrequent

Serum markers ? Melatonin ? Melatonin None

Hemorrhage Yes No No

Other Large, irregular shape Small Tectal plate location, aqueductal obstruction

CT, computed tomography.





that the pineal gland may regulate human response to diurnaldaylight rhythms.

Pineal region masses may cause hydrocephalus throughobstruction of the aqueduct of Sylvius, precocious puberty, orparesis of upward gaze (Parinaud syndrome).

Tumors of Germ Cell OriginGerminoma The most common pineal tumor of the germ cell line is the ger-

minoma, accounting for 60% of pineal germ cell tumors and 40%of pineal region masses. It has also been termed seminoma anddysgerminoma in the medical literature. This tumor, as in all germcell tumors, has a distinct male predominance when seen in thepineal region (in some series as high as 33:1) and a slight femalepredilection when seen suprasellarly. The tumor may be multi-focal in suprasellar and pineal locations. It is a tumor of adoles-cence and young adulthood, rarely seen in patients older thanage 30 years. Germinomas are far more common in the Asianpopulation. Parinaud syndrome and hydrocephalus due to aque-ductal obstruction are the most frequent symptomatology in thepineal site, with diabetes insipidus and visual field deficits mostfrequent in the suprasellar location. Precocious puberty second-ary to expressed hormones may also occur.

The characteristic appearance of the germinoma is that of a

hyperdense mass on unenhanced CT, which enhances markedly(Fig. 3-53). The tumor engulfs the pineal gland, and this has ledto some confusion regarding whether the tumor calcifies. It is cur-rently believed that there is a high incidence of pineal gland calci-fication in patients with germinomas but that the tumor itself doesnot calcify. On MR the germinoma has intermediate signal intensityon T1WI and, because of the tumor cells’ high nucleus/cytoplasmratio, a slightly hypointense signal (similar to gray matter) on T2WI.The mass enhances. Germinomas are very radiosensitive and alsorespond well to chemotherapy. CSF seeding is not uncommon.The best imaging study to evaluate for CSF seeding is contrast-enhanced MR of the entire neuroaxis; nonetheless, repeated CSFcytologic studies are still more sensitive than imaging.

Most of the remaining CNS germinomas occur in the supra-sellar cistern regions (Fig. 3-54), but some have been reported tooccur in the basal ganglia and thalami as well. In these locations

they still are hyperdense on CT but seem to have a higher rate ofcystic degeneration and calcification. Ipsilateral cerebral hemiat-rophy and brain stem hemiatrophy can occur when the germino-

mas are located in these sites.Germinomas with cystic components respond more slowly to

radiotherapy than those that are predominantly solid. The loca-tion, size, and presence of CSF seeding did not influence long-term response.

Teratoma The other tumors of the germ cell line may have unique appear-ances. Teratomas may have fat, bone, calcification, cysts, seba-ceum, or other dermal appendages associated with them. Thelipid and calcification or bone have distinctive CT and MRdensities or intensities. A chemical shift artifact may signal thepresence of fat rather than blood on the T2WI. Enhancementis irregular because of the nonenhancing fatty or calcified

FIGURE 3-53. Germinoma in stereotactic biopsy frame. A hyperdensemass in the pineal region is seen on this unenhanced or enhanced com-puted tomography scan.

A

B

FIGURE 3-54. Suprasellar germinoma. A, An enhancing suprasellarmass is seen infiltrating the optic chiasm on the coronal scan. B, AxialT2-weighted image shows the low signal you would expect for this tumor(arrows).





component. Teratomas are the second most common pineal regiongerm cell neoplasm, but they also abound in the suprasellar cis-tern. In neonates they may diffusely invade a hemisphere or thesacral spine.

Choriocarcinoma Choriocarcinoma has a distinctive feature: It is commonlyhemorrhagic. Teratomas and choriocarcinomas as well as

embryonal cell carcinoma and endodermal sinus tumors aremore common in male patients and have a worse prognosis.Choriocarcinoma is positive for human chorionic gonadotropin(HCG) and human placental lactogen on immunohistochemis-try. The others are not.

OthersYolk sac tumors often show more cystic change than other germcell line lesions. Embryonal carcinoma is solid most commonly.α-Fetoprotein titers are negative in embryonal cell tumors butpositive in yolk sac tumors. Placental alkaline phosphatase char-acterizes the embryonal tumor.

Tumors of Pineal Cell OriginPineoblastoma The incidence of intrinsic pineal cell tumors—pineocytomasand pineoblastomas—is nearly evenly split between male andfemale patients, and the tumors account for 15% of pineal regionneoplasms. The pineoblastoma occurs in a younger age group(peak in first decade of life) than the pineocytoma and is classi-fied as WHO grade IV. Pineoblastomas may occur in associationwith retinoblastomas, and interphotoreceptor retinoid-bindingproteins can be seen in pineoblastomas. Their appearance atimaging is nearly identical, but pineoblastomas may be slightlymore invasive and larger than pineocytomas and have a higherrate of subarachnoid seeding. Again, because these tumors areof the round cell variety with high nucleus/cytoplasm ratios,they often will be dense on unenhanced CT and intermedi-

ate in signal intensity on T2WI (Fig. 3-55). They enhance viv-idly. Calcification is not common yet may be intrinsic to thetumor rather than within the pineal gland itself. Alternatively,the pineal gland calcification may appear exploded as it is dis-placed peripherally by the pineal tumor. We say germinomas“engulf” the pineal gland, and pineoblastomas “explode” thegland.

The 5-year prognosis for pineoblastomas is 58%.

Pineocytoma Pineocytomas are slower-growing pineal parenchymal neoplasms,WHO grade II, that have a peak incidence at age 10 to 19 yearsbut can occur in any age group. In fact the mean age is in the30s. These tumors are smaller than the pineoblastomas, often less

than 3 cm in size, and they may demonstrate a higher rate of calci-fication or cyst formation than their nastier brother the pineoblas-toma. The 5-year prognosis is 86%.

Because the signal intensity characteristics of pineal paren-chymal tumors, malignant germ cell tumors, germinomas, andgliomas may overlap, some investigators have suggested thatserum markers may be more specific than imaging features forhistology. It is true that some tumors secrete characteristic mark-ers, and these are summarized in Tables 3-15 and 3-16.

Pineal Cyst Pineal and tectal gliomas, cavernous hemangiomas, menin-giomas, and benign cysts also populate this area, but they are

peripheral to the pineal gland. Pineal cysts are particularly common, and because some pineal masses (pineocytomas) may becystic, it is important to attempt to identify a solid portion to thelesion to distinguish between the two (Fig. 3-56). Cysts in thepineal region are like those mysterious chocolates in the boxyou never know what’s inside them, which ones are good, whichones are bad. Contrary to what has previously been writtenpineal cysts may compress or occlude the aqueduct, and may be

B C

A

FIGURE 3-55. Pineoblastoma. A, Axial T2-weighted image shows a pineamass that is intermediate in signal intensity with some heterogeneity to thelesion. Low signal is characteristic of the highly cellular primitive neuroecto

dermal tumors. Note the dilation of the third ventricle and occipital horns othe lateral ventricles caused by the compression of the aqueduct, signifyinghydrocephalus. Subarachnoid seeding (arrows) in the form of sugarcoating(B) or gumdrops on the cauda equina (C) is not unusual in pineoblastomas





calcified. They may be round or oblong and can be equal to orgreater than 2 cm in size. The key to distinguishing a pineal cyst

from a cystic astrocytoma is the lack of growth during long-termfollow-up. Because pineal cysts are often surrounded by the twolimbs of the internal cerebral veins, one must be careful not tomisread vascular enhancement as solid mass enhancement.

Benign pineal region cysts can masquerade as any number ofpineal region neoplasms. They can be found in up to 40% of indi-viduals on autopsy studies and probably form in late childhood andregress in late adulthood. The cysts may demonstrate peripheralcalcification or enhancement, fluid-fluid levels, hemorrhage, masseffect, and growth with time. Another potential pitfall is that, despitetheir CSF content, pineal cysts do not have the same intensity asCSF on FLAIR, T1-weighted, or proton density-weighted series.This may be due to hemorrhage, hemorrhagic debris, or high pro-tein seen histologically in these cysts. They may cause symptomsof headache, diplopia, nausea and vomiting, papilledema, seizures,

and Parinaud. Hydrocephalus may be produced by the benign cyst,and sometimes you can have pineal apoplexy where the pineal cystacutely hemorrhages. In follow-up a benign pineal cyst usually staysthe same size (75%), but some regress and some enlarge by as muchas 2 to 3 mm. The point is that they should be treated with respect,watched carefully and, if need be, resected just as one would treat aneoplasm in this location. Obviously there is no risk of subarachnoidspace seeding and the follow-up may be less rigorous.

Nonneoplastic Masses

CystsColloid Cyst A colloid cyst (neuroendodermal or paraphyseal cyst) arises in theanterior portion of the third ventricle near the foramen of Monro.They occur with an incidence of three cases per one million indi-viduals per year. Positional headaches or hydrocephalus may bethe presenting complaints in 30- to 40-year-old patients. Suddendeath due to acute hydrocephalus is one scenario. Usually thelesion is hyperdense on CT because of high protein concentra-tion; the same factor may account for its high signal seen 50% ofthe time on T1WI (Fig. 3-57). The rim of the cyst may faintlyenhance. The lesion is lined by simple to pseudostratified epi-thelium, and is well circumscribed. Theories of evolution includethose who believe colloid cysts arise congenitally as a result ofencystment of the ependyma, as persistence of the paraphysis (a

piece of the diencephalic roof behind the interventricular fora-men), or as one of many neuroepithelial cysts. The endodermal(not neuroectoderm) origin of the lesion has led to the moderntheory that the colloid cyst, like the Rathke cyst, is of respiratoryepithelial origin, perhaps from primitive craniopharyngeal origin.MR is predictive of the ease at which colloid cysts can be aspi-rated; if the signal intensity is dark on T2-weighted scans (sig-nifying a high viscosity hyperproteinaceous or cholesterol-laden

A B C

FIGURE 3-56. Cyst or cystic tumor? Although the signal intensity (arrows) on the sagittal T1-weighted ( A ) and FLAIR (B) image is dissimilar to cere-brospinal fluid, this may still represent a benign pineal cyst. C, What to do? This cystic lesion in the pineal gland displaces the pineal calcification apart.Is it a benign cyst or a neoplasm? In the absence of an enhancing mass or hydrocephalus, one should probably follow this lesion conservatively to assessgrowth. If necessary, shunting can be performed, though this patient did not have hydrocephalus.

A B C

R L

A

P

FIGURE 3-57. Colloid cyst. A, On computed tomography the colloid cyst is hyperdense from high protein. B, Sagittal T1-weighted image (T1WI)shows typical bright signal in the mass at the foramen of Monro due to high protein content. C, Although there is ventriculomegaly from the dark cyston T2WI, there is no transependymal cerebrospinal fluid leakage due to longstanding, chronic compensation.





cyst), it will be a bear to aspirate. Rarely colloid cysts may occurwithin the body of the lateral ventricles, fourth ventricle, or out-side the ventricular system. Treatment may include biventricularshunting, cyst resection, or endoscopic coagulation.

Neuroepithelial Cyst Neuroepithelial cysts that may simulate neoplasms often occurwithin the ventricles. Generally, they are centered on the choroidplexus and may occur anew or in association with previous infec-

tions or hemorrhages in the ventricle. The fluid in these cystssimulates CSF on CT and MR but may be bright on T1WI owingto cholesterol debris or high protein concentration. These cystsare lined by epithelium. They can also occur in the spinal canal,parenchyma (Fig. 3-58), or extra-axial intracranial space.

Neuroenteric Cyst Neuroenteric cysts are lined by cells of endodermal origin andrarely occur in the CNS. When they are seen in the CNS, theyusually occur in the intradural extramedullary spaces of the cervi-cothoracic region, although intracranial cases have been reported.

They are typified by bright signal on T1WI secondary to highprotein concentration. They will not enhance. Differential diagnosis would include epidermoid cysts, Rathke cleft cysts, andtraumatized arachnoid cysts.

When one sees an intraventricular cyst, the differential diagnosis should include a choroid plexus cyst, an ependymal cyst, acolloid cyst, and a cysticercal cyst. Ependymal cysts occur in thefrontal horns of the lateral ventricles and are asymptomatic unlesthey obstruct the foramen of Monro.

Lhermitte-Duclos DiseaseLhermitte-Duclos disease involves a masslike lesion usually seenin the cerebellum as a diffusely infiltrative process. It is correctlyclassified as WHO grade I and termed a dysplastic gangliocytomaThe lesion affects cerebellar gray and white matter and is hyperintense on T2WI (Fig. 3-59). Other names for this entity includediffuse ganglioneuroma, Purkinjeoma, diffuse hypertrophy, granule cell hypertrophy, and dysplastic gangliocytoma. LhermitteDuclos disease usually presents in patients in their early 20s, withsymptoms of increased intracranial pressure or ataxia. Cowden

A B

C D

FIGURE 3-58. Neuroepithelial cyst. A, Unenhanced T1-weighted sagittal scan

shows a multiloculated cystic lesion in theright thalamus. B, Coronal T2-weightedscan shows no significant mass effect andhigh signal similar to cerebrospinal fluid(CSF). C, The FLAIR scan also showsintensity identical to CSF. D, There isno contrast enhancement. This may rep-resent a neuroepithelial cyst, which is abenign lesion that does not require sur-gical intervention. Differential point:Arachnoid cysts are usually not intraparen-chymal, but can exist along perivascularspaces. This could be a huge Virchow-Robin space in fact.





syndrome, which is associated with multiple hamartomas andneoplasms (especially of the breast) is associated with almost 50%of cases of Lhermitte-Duclos disease. It is transmitted on chro-mosome 10q23.

ChoristomasChoristomas are masses of normal tissues in aberrant locations,containing smooth muscle and fibrous tissues. They may behypervascular. Cases have been described in extra-axial loca-tions, including the sella and parasellar regions, as well as theinternal auditory canals associated with the facial and vestibulo-cochlear nerves. Choristomas may enhance and hence may simu-late schwannomas.

Amyloid Amyloid may be deposited in the dura and may simulate menin-giomas, dural lymphomas, or plasmacytomas, with reasonably lowsignal intensity on T2WI. Intraparenchymal amyloidomas are denseon CT and bright on T1WI. Mixed to low intensity on T2-weightedsequences and contrast enhancement have been reported.

Heterotopias and focal areas of abnormal sulcation may alsopresent as masslike lesions. These entities are described morefully in Chapter 9.

Pretreatment Evaluation

The ability of neuroradiologists to predict the grade of a tumorvaries by the criteria used. Certainly the presence of necrosisshould imply a GBM, and a nonenhancing tumor without edema

would imply a low-grade astrocytoma. Although enhancementseems to be a good criterion to suggest higher grade, it is about asaccurate as checking the patient’s age. The older the patient themore likely the tumor is of higher grade. It is rare to see an octo-genarian with a low-grade astrocytoma and equally unusual to seea child with a GBM.

Recently, there have been several intriguing reports show-ing that perfusion scanning can separate high- from low-gradetumors. Just as GBMs have neovascularity histologically, so alsodo they have higher cerebral blood flow on perfusion imaging.This has been used to direct biopsies into the “more malig-nant” region. By the same token, PET scanning has been usedto determine grades of tumor with higher blood flow or glu-cose metabolism corresponding to higher grade. Higher choline,

Cho/NAA ratios greater than 2.2, and higher CBV are other find-ings that may indicate higher grade. Lower grade tumors havehigher myoinositol levels. Other groups have shown a 90% sen-sitivity and specificity for separating low- and high-grade astro-cytomas by setting a mean FA level of 0.141 and maximum FAof 0.244 across all slices through the tumor. FA seems to do bet-ter than using ADC values. Areas of restricted diffusion may por-tend progression of enhancing tumor, and one may direct moreaggressive treatment to these areas. Once again, no neuroradio-logic interpretation is going to stop a neurosurgical biopsy of apresumed astrocytoma. However, we may be able to eliminatesome cases of sampling error by directing that biopsy to the highperfusion, high activity, high-grade region. Maybe then the neu-

rosurgeons will throw us a bone every once in a while.The other recent additions to our armamentarium are thetrue functional studies. For lesions adjacent to eloquent cortex(by this we mean near the speech, memory, or motor areas), it ishelpful to the neurosurgeons for us to show them where thesecritical areas are so that they can reduce the operative morbid-ity associated with the resection. Functional MRI (fMRI) can beused preoperatively to define the speech areas in relation to thetumor or even intraoperatively to direct the surgical resection toinclude the maximum amount of tumor and minimal amount ofeloquent cortex.

Magnetoencephalography (MEG) is another technique thataffords the temporal resolution of the electroencephalogramto map the brain superimposed on a co-registered MR image.Right now the war between the better spatial resolution fMRIand the better temporal resolution MEG is being won by fMRIon the basis of greater availability of MR scanners. It used totake the latest new-fangled scanner to do fMRI. Now any prac-titioner with a decent gradient system MR machine can do tire-kicker motor and auditory mapping. Trust us—even we can doit. A word of caution, the blood oxygenation level-dependentfMRI contrast effect may be reduced near an astrocytoma sec-ondary to (1) compression of vessels, (2) vasoreactive substances(nitric oxide), (3) neurotransmitter substances expressed bytumors, (4) reduced neuronal function, and (5) invasion ofvascular structures by the tumor.

Molecular ImagingThe future is in imaging molecular markers of CNS tumors.Epidermal growth factor receptor (EGFR) gene amplification

A CB

FIGURE 3-59. Lhermitte-Duclos disease. A, Enhanced computed tomography reveals a nonenhancing mass lesion in the superior left cerebellum. Notethe slight low density within the nonenhancing mass. B, T2-weighted image (T2WI) of the lesion again demonstrates the obvious mass effect and highintensity striations within the mass. Notice that the intervening tumoral parenchyma has similar intensity to normal cerebellum.C, In a different case ofLhermitte-Duclos disease, the sagittal T1WI displays a serpentine low intensity pattern with mass effect. These findings are virtually pathognomonicof Lhermitte-Duclos disease.





in association with inactivation of tumor suppressor genes onchromosome 10 are found in the progression from anaplasticastrocytoma to GBM. Vascular endothelial growth factor expres-sion reflects tumor vascularity and may predict response todirected antimarker therapy. Can we vaccinate people to thesemarkers and have host response counteract tumor growth? Canwe determine these levels by imaging without the need for tis-sue samples? If we can image MGMT (O6-methylguanine-DNAmethyltransferase) DNA-repair gene, we can predict response to

medications that promote methylation, leading to favorable (??—extra 3 months of life) outcomes in patients with GBM. Thirtypercent of astrocytomas express a deficiency in TP53, a tumorsuppressor gene on chromosome 17p, which encodes the p53 pro-tein. Imaging the p53 mutation will predict greater GBM necro-sis and usually suggests that the GBM arose from a lower gradetumor. Can we predict which low-grade astrocytomas will prog-ress to GBMs? If so we can be more aggressive therapeuticallyin those that have this p53 mutation. Oligodendrogliomas showallelic losses at the 1p and 19q chromosomes, whereas anaplas-tic astrocytomas and oligoastrocytomas have losses also at 9p and10. The 1p19q deletion predicts worse prognosis in oligodendro-gliomas than those without the deletion. Molecular imaging maylead to targeted therapies and better prediction of outcome andresponse to therapy.

Posttreatment Evaluation

PostoperativeDetermining whether residual neoplasm is present in the postsur-gical tumor bed is one of the most daunting tasks facing a neurora-diologist. What hangs in the balance are prognostic considerationsfor the patient (Table 3-17), potential repeated surgeries, andnonsurgical therapeutic decision-making. A postoperative scanafter a “complete resection” that is interpreted by the radiologistas a small biopsy is frustrating to the neurosurgeon. He wants tosay that he has a clean plate after the meal. Here is how you canavoid this pitfall and why it is such a problem.

Surgical margin contrast enhancement, almost always presentafter the second postoperative day, is usually thin and linear. Themargin may become thicker or more nodular after a week. It thus

becomes difficult to tell whether enhancing tissue in a surgical bed isdue to granulation tissue or marginal tumor enhancement (providedthat the tumor enhanced preoperatively). The granulation tissueenhancement may persist for months postoperatively, but intraparen-chymal enhancement and mass effect after 1 year should be viewedwith suspicion. Dural enhancement is nearly always seen even at1 year and can persist as long as decades after surgery. Enhancementappears sooner and persists longer on MR than on CT.

This has led neurosurgeons to scan patients soon after oper-ation, before this scar tissue has time to develop, to identifyresidual tumor. A scan within 48 hours showing enhance-ment in the surgical bed should lead one to suggest residualneoplasm (Table 3-18). Unfortunately, the hemorrhagic blood

products from the surgery usually have not resolved by 48hours, and one is forced to interpret enhancement on CT andMR against a bright background of blood products. Herein liethe difficulty and points up the absolute requirement of precontrast scans in the same plane and location as the postcon-trast studies. These scans are viewed side by side to detect theextra thickness of enhancement along a hematoma cavity.

Clearly the best way to distinguish blood from granulationtissue from recurrent or residual tumor is to scan sequentially

Blood resolves, granulation stays the same or decreases in sizeand tumor grows.

PostradiationPatients undergoing radiation for primary brain tumors, skullesions, or intracranial metastasis frequently exhibit central andcortical parenchymal loss. The radiologist’s challenge in the postradiotherapy evaluation is to differentiate residual or recurrent tumofrom radionecrosis. Several factors influence the development oradiation necrosis. These include total dose, overall time of administration, size of each fraction of irradiation, number of fractions peirradiation, patient age, and survival time of patients. As patientssurvive longer with more effective treatment, the incidence of radiation necrosis will rise, because it is usually a late effect of treatment (Fig. 3-60). The signs and symptoms of radiation necrosis are

nonspecific and do not differentiate it from recurrent tumor.The effects of irradiation have been separated into those occurring early (within weeks) and late (4 months to many years later(Table 3-19). The former is transient, may actually occur duringradiotherapy, and is usually manifested by high signal intensityin the white matter caused by increased edema (beyond thatassociated with the tumor). The delayed effects are separated intoearly delayed injury (within months after therapy) or late injury(months to years after therapy). Early delayed injury is also a transient effect and is of little consequence other than recognizing ias such (as opposed to tumor growth) directly after therapy. Thelate effects are usually irreversible, affect white matter to a muchgreater extent than gray matter, and histologically involve vascular changes that include coagulative necrosis and hyalinizationThe late injury to the brain may be focal or diffuse and occurs inapproximately 5% to 15% of irradiated patients. Seventy percen

of focal late radiation injuries occur within 2 years after therapy.Pathologically the mechanism of late injury is vascular with

fibrinoid necrosis of small arteries and arterioles. Demyelinationis a concomitant feature with myelin dropout.

Unfortunately, it is exceedingly difficult to make the diagnosis of focal radiation injury. CT or MR may demonstrate a masslesion associated with edema, low in attenuation on CT andhigh in signal on T2WI, which usually enhances. The possibility of focal radiation injury needs to be raised when the lesion ifound in the appropriate temporal sequence to treatment. If thelesion is remote from the primary tumor site, then the diagnosiis more easily suggested. Unfortunately radiation necrosis favorthe primary tumor site, probably because of predisposing vascular effects (see Fig. 3-60). The diagnosis of radiation necrosi

TABLE 3-17.5-Year Survival Rates by Tumor Type

Neoplasms Survival (%) at 5 Years

Pilocytic astrocytoma (WHO I) 87%

Ependymoma 64%

Oligodendroglioma 62%

Mixed glioma 59%

Embryonal type 51%

Diffuse astrocytoma (WHO II) 49%

Anaplastic astrocytoma (WHO III) 30%

Glioblastoma multiforme (WHO IV) 3%

TABLE 3-18. Scar versus Residual Tumor

Feature Scar Tumor

Enhancement within1–2 days

No Yes

Enhancement after 3–4 days Yes Yes

Change in size with time Decreases Increases

Type of enhancement Linear, outside

preoperative tumor bed

Nodular,

solid

Mass effect/edema Decreases Increases





is made by surgical biopsy but may be suggested by PET scan.Distinguishing radiation necrosis from tumor has been the justifi-cation of many PET ventures. The bottom line is where there isradiation there is often tumor. A summary of the invaluable workin this field is found in Table 3-20.

With residual or recurrent tumor 18FDG PET has increased activ-ity (greater than normal brain tissue), whereas radiation necrosisshows low activity. Overall accuracy of PET is approximately 85%for distinguishing residual or recurrent tumor from radiation necro-sis. Some have recently challenged this number as having been

artificially inflated by members of the “mushroom cloud commu-nity” (nuclear medicine docs). The accuracy rates are better forhigh-grade tumors than for low-grade tumors, probably becauseof inherent differences in tumor growth activity. Removal of thenecrotic irradiated nonneoplastic tissue and steroid therapy are thetreatments of choice and may be curative. Focal hemorrhage with-out necrosis also occurs as a result of radiation.

Thallium-201 SPECT has also been advocated for differentiatingtumor recurrence from radiation necrosis in patients who have under-gone gamma knife radiosurgery or in those who receive radiationtherapy. Although sensitivity for tumor is high, specificity is moder-ate with this technique. Some have suggested that methionine-11CPET can better outline tumors as areas of increased accumulationof methionine-11C, regardless of grade of tumor.

A B C

FIGURE 3-60. Radiation necrosis. This patient had resection of an anaplastic astrocytoma of the right occipital lobe and was treated with radiation ther-apy. A, FLAIR scan demonstrates high signal intensity without mass effect in the right temporal and occipital lobe with dilatation of the right occipitalhorn of the lateral ventricle. Note the high signal intensity in the left basal ganglia. B, T1-weighted scan shows a high intensity focus in the pulvinarregion of the right thalamus secondary to a telangiectasia from radiation therapy. The right basal ganglia are bright but the left are dark. C, On the post-

contrast scans, the left basal ganglia enhance. This was an area of radiation injury.

TABLE 3-19. Types of Radiation Injuries

Feature Early Early Delayed Late Delayed

Time course During therapy <3 mo after therapy >3 mo after therapy

Manifestation Transient increase in whitematter edema

Transient increase in whitematter edema

Focal or diffuse longer-lasting whitematter changes

Contrast enhancement No Rare Not uncommon

Long-term sequelae None None Vasculitis, demyelination

Calcification seen No No Yes, in children

Disseminated necrotizingleukoencephalopathy

No No Rarely, with chemotherapy

Symptoms reversible Yes Yes NoTelectangiectasia No No Yes

Hemorrhage present No No Often

TABLE 3-20. Distinction Between Tumorand Radiation Necrosis

Feature

Residual orRecurrent Tumor

Radiation Necrosis

Timing Immediate ordelayed

Months to years

Mass effect/edema Present Present

Enhancement Yes Yes, soapbubbles orSwiss cheese

PET (18-FDG) Positive Negative

SPECT (Thallium-201,methionine-11C)

Positive Negative

MRS Elevated choline Decreasedcholine

Perfusion-weighted MR Elevated rCBV Decreased rCBV

FDG, fluorodeoxyglucose; MRS, magnetic resonance spectroscopy; PET, positronemission tomography; rCBV, relative cerebral blood volume; SPECT, single-photonemission computed tomography.





Some investigators are using MRS and perfusion imaging todetermine whether necrotic areas after radiotherapy are due totumor or radiation. Areas of radiation damage without neoplasmshow markedly reduced choline levels, whereas tumor is usuallyassociated with elevated choline residues. Furthermore, radiationdamage is hypoperfused; most high-grade tumors show increasedflow. Relative CBV maps appear to be complementary to MRSin detecting nonviable tissue. These techniques haven’t quitereplaced PET yet, but they are on the rise in academic circles.

Diffuse late injury to the brain takes the form of severe demy-elination, particularly in periventricular and posterior centrumsemiovale regions. CT demonstrates decreased white matter den-sity, but T2WI is more sensitive and shows high signal intensity inthe white matter. Usually the abnormality does not show enhance-ment. It is estimated that with whole brain irradiation, diffusewhite matter changes may occur in 38% to 50% of patients. Theincidence increases with increasing patient age. Clinical findingsdo not correlate well with severity of white matter injuries.

Disseminated necrotizing leukoencephalopathy is a severeform of radiation-related injury usually seen in conjunction withchemotherapy, whether intrathecal or intravenous. Most patientswith disseminated necrotizing leukoencephalopathy do extremelypoorly. This entity is described more fully in Chapter 7.

Radiation may induce a mineralizing microangiopathy, causing

calcification in the basal ganglia or dentate nuclei, with rare cerebralcortical involvement associated with atrophy of intracranial struc-tures. This generally occurs more than 6 months after radiation andis more common in children than in adults. The cause is thought tobe an intimal injury to small vessels with associated tissue hypoxiaand dystrophic calcification. Frank radiation vasculitis in large ves-sels may also be seen as focal narrowed segments on angiograms.

Telangiectasias or other occult cerebrovascular malformationsmay occur as a delayed complication to radiation therapy (seeFig. 3-60). This may manifest by hemosiderin-laden deposits inthe brain most evident on T2* scans. In children, a vasculopathyleading to intracranial hemorrhage can be seen in radiated brainswith or without concomitant chemotherapy.

Graft-versus-Host DiseaseDisoriention, tremors, and myoclonus may be the clinical pre-sentation of graft-versus-host disease (GVHD). MR images mayshow abnormal signal in the brain stem and deep white matter.The findings may resolve after steroid treatment.

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