05 -DISORDERS of HISTOGENESIS _ NEUROCUTANEOUS SYNDROMES .

NEUROFIBROMATOSIS Neurofibromatosis is not a single entity but is actually a group of heterogeneous diseases.2 Although several variants of neurofibromatosis have been proposed, to date

Von Hippel-Lindau Syndrome

Other Neurocutaneous Syndromes

Epidermal Nevus Syndrome

Basal Cell Nevus Syndrome

Miscellaneous Melanocytic

Phakomatoses

Cowden Disease

Neurocutaneous syndromes are also known as

phakornatoses (the Greek roots of the word phakomatosis

have been described-with varying degrees of accuracy-as

meaning birthmark, lentil bean, freckle, or spot).1 This

heterogeneous group of disorders generally has central

nervous system and, for the most part, cutaneous

manifestations Many of the neurocutaneous syndromes

also have prominent visceral and connective tissue

abnormalities Several different phakornatoses have been

described; the major, and some of the more interesting but lesscommon, neurocutaneous syndromes are listed above Only the principal disorders will be discussed in depth; some of the uncommon neurocutaneous syndromes are described briefly

NEUROFIBROMATOSIS Neurofibromatosis is not a single entity but is actually a group of heterogeneous diseases.2 Although several variants of neurofibromatosis have been proposed, to date the National Institutes of Health (NIH) Consensus Development Conference has defmed only two distinct types: Neurofibromatosis type 1 (NF-1, von Recklinghausen disease, sometimes termed peripheral neurofibromatosis) and neurofibromatosis type 2 (NF-2, bilateral acoustic schwannomas or "central" neurofibromatosis) 3 Because NF-1 often has central lesions and NF-2 can occasionally have peripheral manifestations the terms central and peripheral neurofibromatosis have been discarded

Neurofibromatosis Type 1 (von Recklinghausen Disease)

Incidence and inheritance NF-1 is the most

common of all the phakornatoses and accounts for more than 90% of all neurofibromatosis cases NF-1

is one of the most common single gene congenital syndromes, with a reported incidence of one in 2000

to

C H A P T E R

3000 live births The responsible gene is on the long

arm of chromosome 17 A high mutation rate occurs

at this locus because approximately 50% of patients

with NF-1 are new mutations in whom a family

history of the disease is absent Inheritance is

autosomal dominant with high penetrance but very

variable expressivity.1

Diagnostic criteria Diagnosis of NF-1 is

established when two or more of the following

findings are present3:

Six or more 5 mrn or larger cafe-au-lait spots

One plexiform neurofibroma or two or more

neurofibromas of any type

Two or more pigmented iris hamartomas

(so-called Lisch nodules)

Axillary or inguinal region freckling

Optic nerve glioma

First-degree relative with NF-1

Presence of a characteristic bone lesion (e.g.,

dysplasia of the greater sphenoid wing,

pseudarthrosis)

To date, the Consensus Panel criteria have not been

revised to include the characteristic MR findings

reported in NF-1 (see subsequent discussion)

Pathology and imaging Lesions in NF-1 may

include the following:

Nonneoplastic "hamartomatous" lesions

White matter lesions

Basal ganglia lesions

Skull and meningeal dysplasias, other osseous

lesions

Spine, cord, and nerve root lesions

Miscellaneous lesions (including non-CNS)

Eye and orbit abnormalities

Vascular abnormalities

Visceral, endocrine tumors

CNS manifestations occur in 15% to 20% of all

patients with NF-1 (see box)

Many somatic manifestations of NF-1 are age

related; external stigmata may be subtle or absent in

very young children Cutaneous lesions and tumors at

all sites generally increase in size and number with

increasing age 2

Neoplasms The increased risk of developing a

CNS neoplasm in a patient with von Recklinghausen

neurofibromatosis has been estimated to be four

times that of the general population.4 The neoplasms

reported in NF-1 are typically lesions of neurons and

Neurofibromas of spinal/peripheral nerves Scattered

Plexiform Osseous/dural lesions Hypoplastic sphenoid wing Sutural defects

Kyphoscoliosis Dural ectasia Meningioceles Ocular/orbital manifestations Optic nerve glioma Lisch nodules in iris Buphthalmos (cow eye, or macrophthalmia) Retinal phakomas

Plexiform neurofibroma (CNV1 most common)

Vascular lesions Progressive cerebral arterial occlusions Aneurysms

74 PART ONE Brain Development and Congenital Malformations

Fig 5-1 A, Gross pathologic specimen of the brain, seen from below, of a patient with

neurofibromatosis type I (NF-1) Bilateral optic nerve gliomas (arrows) are present B, Coronal cut

section shows that the glioma involves the optic chiasm (large arrows) Also seen are multiple basal ganglionic and white matter hamartomatous lesions (small arrows), characteristic of NF-1 (Courtesy

C Petito.)

The common CNS tumor in NF-1 is optic nerve

glioma, occurring in 5% to 15% of cases, although

only about one quarter of all patients with optic nerve

gliomas have NF-1.6 Optic nerve gliomas can involve

one or both optic nerves and commonly extend into

the chiasm (Figs 5-1 and 5-2) Posterior involvement

of the optic tracts, lateral geniculate body, and optic

radiations occurs but is less common (Fig 5-3).7 Most

optic nerve gliomas are histologically benign,

lowgrade astrocytomas (usually the pilocytic type)

that behave clinically more like hamartomas than

malignant neoplasms,1,8 although up to 20% of all

chiasmal gliomas in children may behave aggressively

with fatal results.9

Imaging of optic nerve gliomas and their posterior

extension is best delineated by magnetic resonance

imaging Most of these neoplasms are hypo- to

isointense on T1-weighted scans and show increased

signal on T2WI Contrast enhancement is variable;

Fig 5-2 Axial CT scan in a child with neurofibromatosis

type 1 shows bilateral optic nerve gliomas (arrows)

Fig 5-3. Postchiasmatic spread of optic nerve gliorna in a patient with neurofibromatosis type 1

Axial (A andr B) and sagittal (C) postcontrast

T1-weighted MR scans show that the left optic nerve glioma extends posteriorly into the chiasm, hypothalamus, medial temporal lobe, and pons

(arrows)

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes 75

AA

Fig 5-3, cont'd D to H, Axial T2-weighted studies demonstrate the optic nerve

gliorna (curved arrows), which appears slightly hypointense to gray matter, the very hyperintense chiasmatic and retrochiasmatic involvement (large arrows), and

numerous hamartomatous foci of slightly less intense signal in the white matter and

basal ganglia (small arrows)

76 PART ONE Brain Development and Congenital Malformations

hancement is typically absent or minimal in most

cases with opticochiasmatic involvement but can

occasionally be striking, particularly when extension

along the posterior optic pathway is present (Fig 5-3)

Nonoptic gliornas have an increased frequency of

occurrence in NF-I Most are low-grade, relatively

benign astrocytomas of the brain stem, tecturn, and

periaqueductal regions, although more anaplastic

astrocytomas do occur (Fig 5-4) Nonastrocytic

gliomas associated with NF-1 are very uncommon; a

few cases of intracranial e endymoma have been

reported but are uncommon.10

Plexiform neurofibromas are a hallmark of NF-1

and are diagnostic of von Recklinghausen

neurofibromatosis They are found in about one third

of all patients with NF-1.11 Plexiform neurofibromas are multiple, tortuous, wormlike masses that arise along the axis of a major nerve They are unencapsulated and tend to infiltrate and separate the normal nerve fascicles, producing a fusiform appearance.12

Plexiform neurofibromas in the head and neck commonly occur along the first (orbital) division of the trigerninal nerve They often are associated with sphenoid wing dysplasia and middle cranial fossa arachnoid cyst or prominent subarachnoid spaces Plexiform neurofibromas frequently extend posteriorly to involve the cavernous sinus but typically do not extend posteriorly beyond Meckel's cave

Fig 54 A and B, Gross pathologic specimens in a patient with neurofibromatosis

type I (NF-1) and glioblastoma multiforme A, Coronally sectioned brain shows

the hemorrhagic, necrotic tumor in the deep basal ganglia (arrows) B, Spinal cord shows multiple nerve root tumors (arrows) C, Contrast-enhanced axial CT

scan in another patient with NF-1 Artifact from surgical clip is seen in the sellar region; chiasmatic biopsy several years before the current study disclosed pilocytic astrocytoma A poorly delineated, contrast-enhancing posterior fossa

mass (open arrows) is seen Anaplastic astrocytoma was found at craniotomy (A

and B, Courtesy E Tessa Hedley-Whyte.)

CT scans show a poorly delineated mass in the

high deep masticator space that often involves the

orbit and cavernous sinus On MR scans, plexiform

neurofibromas are typically isointense with muscle

on T1-weighted sequences and enhance strongly

following contrast administration (Fig 5-5).13

Sarcomatous degeneration of peripheral soft-tissue

neurofibromas is estimated to occur in 5% to 15% of

all patients with NF-1 Malignant peripheral nerve

sheath tumors in the head and neck arise from the

supraorbital or maxillary branches of CN V and may

diffusely invade the skull base A neurofibrosarcoma

of the spinal nerve roots can invade the spine (see

subsequent discussion)

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes 77

Nonneoplastic "hamartomatous" lesions Benign brain parenchymal abnormalities are observed in nearly 80% of all patients with NF-114 (Figs 5-1 and 5-6 to 5-9) Multiple lesions in the basal ganglia, optic radiations, brainstem, and cerebral pecluncles are common.2,5 Pathologically these lesions are foci

of hyperplastic or dysplastic glial proliferation and

considered malformative rather than neoplastic.5a Ninety per cent of the white matter lesions in NF-1 show no mass effect or enhancement after contrast administration Although the white matter lesions may increase in size or number in early childhood, they typically diminish with age; some are occasionally observed into adulthood, however (Fig 5-7).14

Fig 5-5 Plexiform neurofibromas in neurofibromatosis type 1 (NF-1) A, Gross

pathologic specimen of the eye and periorbital soft tissues in a patient with NF-1

Buphthalmos (cow eye) is present with a large plexiform neurofibroma of the eyelid

(arrows) Sagittal (B) and axial (C) T1-weighted MR scans with contrast enhancement

show the poorly delineated plexiform neurofibroma infiltrating the soft tissues of the eyelid, high deep masticator space, retrobulbar soft tissues, and cavernous sinus

(arrows) (A to C,Courtesy B Haas and A Hidayat.) Continued.

Uncommonly, moderate mass effect can be observed

(Fig 5-9) and contrast enhancement can occur (Fig

5-8, F and G)

The significance of the high signal intensity lesions

that enhance following contrast administration

remains undetermined.5a Caution against aggressive

operative and adjuvant therapy for brain stem lesions

in these patients has been recommended because the

few cases that have come to biopsy or autopsy have

largely demonstrated benign pathology.10,15

In a recent longitudinal series, none of the white

matter lesions seen in NF-1 evolved into a

neoplasm.14 Interval MR imaging follow-up of

atypical lesions (large size, mass effect, contrast

enhancement, proximity to an optic pathway glioma)

is recommended.2

Basal ganglia lesions, primarily involving the

globus

Fig 5-5, cont'd D to F, Axial MR studies in another

patient with a plexiform neurofibroma along the facial nerve cutaneous branches Axial T1- and T2-weighted studies show the diffusely infiltrating

nature of the lesion (D and E, arrows) Postcontrast

fat suppression scan (F, arrows) shows the lesion enhances strongly (D to E, Courtesy K Reynard.)

pallidus, have also been observed in patients with documented NF-1 On CT scans they are seen as relatively well-defined unilateral or bilateral lesions that do not enhance following contrast admiistration.16 On MR studies, high intensity basal ganglia foci are seen on T1-weighted sequences (Figs, 5-8, B, and 5-9, A) They are somewhat

hyperintense on T2WI (see Fig 5-3, A) The lesions

typically do no exhibit mass effect, edema, or contrast enhancemen and do not show progression.17 Uncommonly, some increase in signal after contrast administration can be observed (Fig 5-7) The basal ganglia lesions may represent a different histology from the white matter lesions because their morphology and signal characteristics are often slightly different from the bram stem and cerebellar abnormalities previously discussed (Fig 5-3).5

78 PART ONE Brain Development and Congenital Malformations

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes 79

Fig 5-6 Gross pathology of brainstem and pons in

neurofibromatosis type 1 The pons and midbrain have numerous foci of gliosis, delayed myelination,

and hamartomatous change (arrows) (From archives

of the Armed Forces Institute of Pathology.)

neurofibromatosis type 1 A solitary lesion is present

in the right thalamus that appears low signal on

T1-weighted scans (A, arrow) and hyperintense to brain on T2Wl (B, arrow) Following contrast

administration, the lesion becomes isointense to brain

on T1WI (C)

80 PART ONE Brain Development and Congenital Malformations

scans without contrast enhancement show opticochiasmatic gliorna (A, black arrows) and

high-signal foci in the basal ganglia and thalami (B, black arrows) C, and D, Axial

T2-weighted scans show the chiasmatic glioma is low signal (C, large black arrows). Also seen are multiple foci of increased signal in the medulla, pons, cerebellum, thalami, and

septum pellucidum (C and D, small black arrows) E to G, Postcontrast T1-weighted scans

show that the supratentorial lesions and optic chiasm mass (F, large black arrows) do not

enhance, whereas some-but not all-of the posterior fossa lesions show increased signal (F

and G, small black arrows).

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes 81

Fig 5-9 Neurofibromatosis type 1 A and

B, Axial T1-weighted MR scans without

contrast enhancement show high-signal lesions in the basal ganglia and internal

capsule (A, arrows), as well as the major cerebellar peduncles (B, arrows) The pons

appears enlarged C to E, Axial T2-weighted studies show multiple foci of increased signal in the basal ganglia, internal capsule, pons, medulla, and

cerebellum (arrows) The pons and medulla

are enlarged None of the lesions enhanced after contrast administration (Courtesy S

Lin.)

82 PART ONE Brain Development and Congenital Malformations

Skull, meningeal, and osseous lesions Skull and

dural lesions are common in patients with NF-1.17a

These include macrocrania, hypoplasia of the greater

sphenoid ala with temporal lobe herniation into the

orbit (Figs 5-10, A, 5-11, and 5-12), calvarial defects

(Fig 5-10, B) (the lambdoid suture is a characteristic

location), and dural ectasia Enlargement of the

internal auditory canals can sometimes be seen in

patients with NF-1; this is secondary to dysplastic

dural enlargement, not acoustic schwannoma (which

is a feature of NF-2) Other reported distinctive

osseous lesions in NF-1 include focal overgrowth of a

digit, ray, or an entire limb, tibial bowing, "ribbon

ribs," and pseudoarthrosis.1

Spine, spinal cord, and nerve root Radiologic

abnormalities of the spine in patients with NF-1 are

dura, nerve root, and cord lesions occur

The common spinal abnormality is enlargement of

one or more neural foramina, seen in nearly 60% of

NF-1 patients Most often this is secondary to the

presence of a neurofibroma along the exiting nerve

root (see subsequent discussion); less commonly it is caused by dural ectasia or arachnoid cyst Scalloping

of the posterior vertebral bodies is seen in 10% (Fig 5-13) This finding is nearly always secondary to

dural dysplasia, not neurofibroma.18

Spinal deformities, typically kyphoscoliosis (Fig 5-13, A), also occur, as do meningoceles Multilevel

outpouchings of dura and CSF can be seen Occasionally, meningoceles can become quite large, particularly in the thoracic region.19,20 The osseous and dural lesions seen in NF-1 most likely represent independent derivatives of a common mesenchymal dysplasia.21

Asymptomatic intradural extramedullary masses, typically neurofibroma, are present in nearlt in 20%

of NF-1 patients.18 So-called dumbbell tumors are found on the exitting spinal nerves of 13% to 20% of patients with NF-1 Histologically these are also neurofibromas.22

Fig 5-10 PA (A) and lateral (B) plain skull films in a

patient with neurofibromatosis type 1 show the characteristic findings produced by sphenoid wing hypoplasia On frontal views the orbit appears

"empty" (A, arrows); on lateral views, only a single

curvilinear line is seen representing the normal

greater sphenoid wing (B, large arrow) The other

sphenoid wing is absent In addition to sphenoid hypoplasia, other characteristic skull changes include

sutural defects (B, small arrows) Oblique view (C)

shows enlarged optic canal (arrow) The patient had

an optic nerve glioma

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes 83

Fig 5-11 Neurofibromatosis type 1 with orbital dysplasia, middle fossa arachnoid

cyst, plexiform neurofibroma, and buphthalmos A and B, Coronal CT scans show

the enlarged globe (curved arrow) and plexiform neurofibroma (open arrows) C,

Axial CT scan shows the absent sphenoid wing with arachnoid cyst (double arrows) and temporal lobe protruding through the dehiscent sphenoid bone (curved arrows)

into the orbit The plexiform neurofibroma is indicated by open arrows Reformatted

3-D shows the enlarged, "empty" orbit (arrows) as seen anteriorly (D), as well as

from the posterior, endocranial aspect (E) (Courtesy I Tarwal and M Shroff.)

84 PART ONE Brain Development and Congenital Malformations

Fig 5-12 Axial postcontrast CT scan in a patient

with neurofibromatosis type 1 shows striking

sphenoid wing hypoplasia, and plexiform

neurofibroma (arrows)

Ractiologically the nerve root tumors in NF-1 tend to

be relatively small and scattered (Fig 5-14) Multiple

arachnoid cysts may also develop and protrude along

the course of these roots, mimicking tumors.1

Spinal cord lesions are seen on MR studies in 14%

of NF-1 patients.18 Intramedullary tumors are

typically low grade astrocytoma "Hamartomatous"

lesions similar to those identified in the basal ganglia

and cerebral white matter may occasionally be

identified on high-resolution T2-weighted studies

(Fig 5-15)

Miscellaneous lesions Ocular lesions identified in

NF-1 include Lisch nodules of the iris, foci of

astrocytic proliferation in the retina, and buphthalmos

(macrophthalmia, or cow-eye) (Figs 5-5 and 5-11)

Vascular abnormalities are also associated with

von Recklinghausen neurofibromatosis Whereas

renal and gastrointestinal system lesions are common,

involvement of the craniocerebral vessels is relatively

rare More than 85% of the reported cerebrovascular

lesions are of a purely occlusive or stenotic nature,23

including progressive cerebral arterial occlusive

disease with "moyamoya" pattern of collateral

circulation.24 (Fig 5-16, A and B) Histologic

examination of the affected vessels usually discloses

advanced intimal, and occasionally medial, dysplasia

with marked luminal narrowing.25

Aneurysms are the second most frequently

reportedvascular abnormality in NF-1 (Fig 5-16, C

and D).26-28

Nonaneurysmal vcscular ectasias (Fig 5-16, C and D)

Fig 5-13 Lateral (A) and AP (B) postmyelogram

plain films in a patient with neurofibromatosis type 1 Note marked thoracic kyphoscoliosis and extreme posterior vertebral scalloping secondary to dural dysplasia (A, arrows) Widened interpediculate distance secondary to the pronounced dural dysplasia

is also present (B, arrows)

and arteriovenous fistulae or malformations (Fig.5-16, E) can also occur in association with NF-1.29

Non-CNS lesions Visceral and endocrine tumors

have been reported in about 4% of patients with NF

-1.11

Neurofibromatosis Type 2 Inheritance and incidence Neurofibromatosis

type 2, also known as NF-2 or "bilateral acoustic schwannomas," is a distinct form of the disease that must be separate d clinically and radiographically from NF-1.6 It too is transmitted with autosomal dominant inheritance but has been identified with defects of chromosome 22 NF-2 is much less common than NF-1, occurring approximately once in 50,000 live births

Committee has also defined clinical criteria for NF-2 Bilateral masses of the eighth cranial nerves are diagnostic A patient is also considered to have NF-2

Fig 5-14 A, Oblique plain film

of the cervical spine in a patient

with neurofibromatosis type 1

shows enlarged neural foramina

(arrows) B, Myelogram shows

small extramedullary intradural

filling defects secondary to

neurofibromas (arrows).

Fig 5-15 Sagittal T2-weighted fast spin-echo MR

scan in a patient with neurofibromatosis type 1 and thoracic kyphoscoliosis shows multiple

intramedullary foci of increased signal (arrows) Note

that the cord is not enlarged; the lesions did not enhance after contrast administration and probably represent benign white matter lesions similar to those often observed in the brain

86 PART ONE Brain Development and Congenital Malformations

Fig 5-16 Vascular abnormalities in neurofibromatosis type 1 (NF-1) A and B,

Sevenyear-old child with NFA and acute left-sided hemiplegia at age 2 Right carotid

angiogram, AP (A) and lateral (B) views, shows occlusion of the right proximal middle

cerebral artery (A, large arrow) with basilar and cortical collateral blood flow (small

arrows) to the M1 segment and some of the distal MCA branches Stenoses, slow

antegrade flow, and frank occlusions in more distal vessels are also present (double

arrows) C and D, A 54-year-old oriental male with NFA Lateral (C) and AP (D)

vertebral angiogram shows marked vascular ectasia, tortuosity, and a giant basilar artery

aneurysm (arrows) E, Phase-contrast MR angiogram in a 27-year-old female with NFA shows an arteriovenous malformation (arrows) (A and B, Courtesy D Harwood-Nash C

and D, Courtesy M.H Teng.)

If there is a first-degree relative with NF-2 plus either a

single eighth nerve mass or any two of the following:

schwannoma, neurofibroma, meningioma, glioma, or

juvenile posterior subcapsular lens opacity.1,3 NF-1 and

NF-2 are compared in the boxes, right and p 73

Cutaneous manifestations are.much less common in

NF-2 compared to NF-I Therefore NF-2 patients are

often older at the time of initial diagnosis Cafeau-lait

spots are absent or few; cutaneous neurofibromas and

Lisch nodules are not features of NF-2

Pathology and imaging CNS lesions eventually

develop in virtually all patients with NF-2 and include

the following:

1.Neoplasms

Cranial nerves

Meninges

2 Nonneoplastic intracranial calcifications

3 Spinal cord and nerve root tumors

Neoplasms Type 2 neurofibromatosis seems to be

associated with tumors of Schwann cells and meninges

(Figs 5-17, A, and 5-18) Intracranial schwanno mas

most frequently involve the vestibulocochlear nerves

(Figs 5-17, A, and 5-18, A and E); from 2% to 10% of

all patients with acoustic nerve tumors have NF-2.30

Bilateral acoustic schwannomas are the hallmark of NF-2

and diagnostic of this condition (Figs 5-18, A; 5-20, B;

and 5-21, F) Unilateral acoustic tumors typically arise

from the vestibular nerve and displace the facial and

cochlear nerves around the tumor capsule In NF-2

patients these nerves often

Clinical

Cutaneous manifestations rare

CNS lesions in ~100%

Brain: lesions of schwarm cells, meninges

CN VIII schwannomas most common (bilateral acousticschwannomas diagnostic for NF-2); mul tipleschwannomas of other cranial nerves highly suggestive of NF-2)

Meningiomas; often multiple Nonneoplastic intracranial calcifications (especially choroid plexus)

Spinal cord/roots Cord ependymomas

Multilevel, bulky schwannomas of exiting roots

Meningiomas

Spine Secondary changes (expansion, erosion secondary to cord/root tumors

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes

87

Fig 5-17 Gross pathology specimens from a patient with neurofibromatosis type 2 (NF-2) A,

Bilateral acoustic schwannomas were present; one is cut across and shown here (arrows) B,

The dura over the convexity and parasagittal area contains multiple meningiomas (arrows).

(Courtesy E T edley-Whyte.) Continued

88 PART ONE Brain Development and Congenital Malformations

Fig 5-17, cont'd C, Coronal cut brain specimen shows

abnormally enlarged, calcified choroid plexus (arrow) D,

The spinal cord is enlarged Multiple, rounded, nerve root

schwannornas are present (arrows) E, Cut section through

the spinal cord demonstrates ependymoma (arrows)

(Courtesy E Tessa Hedley-Whyte.)

Fig 5-18 Postcontrast axial CT

scans in a patient with neurofibromatosis type 2 (NF-2) Typical lesions of NF-2 include bilateral eighth nerve schwannomas

(A, arrows); schwannomas of other

cranial nerves (trigeminal

schwannoma in B, open arrow);

nonneoplastic choroid plexus

calcifications (B and C, white

arrows), and multiple meningiomas

(C and D,black and white arrows).

Figure 5-18, cont'd.Five years later, postcontrast MR scans show progression of the lesions

The left-sided vestibulocochlear schwannoma has been resected; the lesion in the right

cerebellopontine angle is larger (E, white arrow) The meningiornas have grown larger (E and

F, black and white arrows) Cervical spine MR scan without contrast enhancement shows

another meningioma at the craniocervical junction (G, black and white arrows) and an intramedullary lesion (G, white arrows) that at surgery was found to be an ependymoma

ter the tumor directly or axe eagulfed by the mass

The bilateral acoustic tumors in NF-2 also sometimes invade the cochlea and temporal bone Stereotactic radiosurgery may be a viable, even preferred, treatment option in some of these patients 31

The trigeminal nerve is the next most frequently involved nerve in NF-2 (Fig 5-18, B) Although isolated schwannomas can occur spontaneously along

other cranial nerves (with the exception of the olfactory and optic nerves, which are really brain tracts), presence of an oculomotor, trochlear, or abducens nerve tumor should prompt investigation for NF-2 (Figs 5-19 and 5-22, C) Involvement of more than one cranial nerve by schwannoma should also raise the suspicion for NF-2 (Figs 5-18 and 5-19)

On imaging studies, schwannomas tend to appear

Fig 5-19 Coronal postcontrast T1-weighted MR scans in a patient with

neurofibromaosis type 2 show multiple meningiomas (open arrows), as well as

schwannomas of the oculomotor (A, curved arrow) and trochlear (B, curved

arrow) nerves

F,

G

90 PART ONE Brain Development and Congenital Malformations

Fig 5-20 Twenty-six-year-old patient with neurofibromatosis type 2 (NF-2)

Precontrast axial T2-weighted (A) and postcontrast T1-weighted scans (B and C) show

bilateral eighth nerve schwannomas (A and B, arrows) and multiple meningiornas (C,

arrows) Also present on precontrast sagittal T1-weighted scans of the brain and

cervical spine are an intraaxial lesion at the cervicomedullary junction (D, arrows) and

an extraaxial lesion at the midcervical level (E, arrows) Postcontrast scan (F) showed

strong but inhomogeneous enhancement of the intramedullary mass (open arrows) and

an unsuspected planum sphenoidale mass (double arrows) The cervicomedullary

junction mass is a spinal cord ependymoma; the planum sphenoidale and extraaxial cervical masses are meningiomas

91 PART ON1E Brain Development and Congenital Malformations

rounded and focal Because they often undergo cystic

degeneration and hemorrhage, their attenuation

characteristics on CT and signal on MR are frequently

iso- or hypodense compared to brain on NECT and

enhancement following contrast administration (Fig

welldelineated masses that are iso- to hypointense

compared to brain on T1-weighted scans and iso- to

hyperintense on balanced and T2WI Strong but

heterogeneous enhancement is typical (Fig 5-20).13

Two thirds of asymptomatic children with NF-2

skin/spine lesions or one parent with the disease have

Intracranial meningiomas are also comynon in

NF-2 They are often multiple (Figs 5-17 to 5-22) Intracranial tumors other than schwannomas and meningiomas are not a feature of NF-2

calcifications in the choroid plexus (Figs 5-17, C, and

5-21), cerebellar cortex, and, occasionally, on the surface of the cerebral cortex are a feature of NF-2.32

Spinal cord and nerve root Spine lesions in NF-2

are very common Multiple intradural, extramedullary soft tissue masses are identified in most patients and

are typically meningiomas (Fig 5-20, E) or

schwannomas (Fig 5-22, A).18 Multilevel masses along the exiting spinal nerve roots can be features of both NF-1 and NF-2 (Figs 5-17, D, and 5-23) In NF-2 cases these are usually schwannomas; 22,33a,33 tissue from these tumors, as well as sporadic spinal schwannomas,

Fig 5-22 Gross pathology of spine and cord lesions in a patient with neurofibromatosis

type 2 A, Multiple spinal schwannomas (large black arrows) and meningiorna (small

black arrows) are seen B, A spinal cord ependymoma is present This patient also had

bilateral oculornotor nerve schwannomas (C, arrows) and multiple intracranial meningiomas (D, arrows) (Courtesy Rubinstein Collection, University of Virginia

Department of Pathology.)

Chapter 5 Disorders of Histogenesis: Neurocutaneous Syndromes 91

Fig 5-21 Nonneoplastic choroid plexus lesions in

neurofibromatosis type 2 A and B, Postcontrast axial

CT scans show extensive nonneoplastic choroid

plexus calcifications (arrows) in this 27-year-old

patient with NF-2 C to F, More extensive choroid

plexus calcifications (large straight arrows), multiple meningiomas (curved arrows), and bilateral acoustic schwannomas (double arrows) are seen on

postcontrast CT scans in this 43-year-old patient with NF-2 (Courtesy Dr J Laothamatas.)

E