AJR 2001; 176:75-82
© American Roentgen Ray Society
Cross-Sectional Imaging of Peripheral Nerve Sheath Tumors
Characteristic Signs on CT, MR Imaging, and Sonography
John Lin1 and
William Martel
1
Both authors: Department of Radiology, The University of Michigan Medical
Center, 1500 E. Medical Center Dr., TC 2910, Ann Arbor, MI 48109-0326.
Received May 4, 2000;
accepted after revision June 8, 2000.
Presented at the annual meeting of the American Roentgen Ray Society,
Washington, DC, May 2000.
Address correspondence to J. Lin.
Introduction
Peripheral nerve sheath tumors are divided into two major benign
categories, neurofibroma and schwannoma, and a malignant form, malignant
peripheral nerve sheath tumor. Each category can be associated with
neurofibromatosis. Although major nerve trunks are most commonly affected,
virtually any peripheral nerve can represent a site of origin.
Our purpose is to illustrate the spectrum of cross-sectional imaging
findings for each type of peripheral nerve sheath tumor. Multitechnique
correlation of CT, MR imaging, and sonography is shown with emphasis on
characteristic signs of peripheral nerve sheath tumors including the
relationship to the nerve, fusiform shape, "split-fat" sign,
associated muscle atrophy, and the MR "target" sign. We also
present the concept of the sonographic target sign, which was recently
described [1] as a sonographic
correlate to the MR target sign.
Neurofibromas
Neurofibromas (Figs.
1A,1B,1C,2A,2B,3A,3B,3C)
most frequently affect patients who are 20-30 years old and represent slightly
greater than 5% of benign soft-tissue neoplasms
[2,
3]. Most lesions are solitary,
but up to 10% are associated with neurofibromatosis. Neurofibromas in the
setting of neurofibromatosis tend to be larger and have a higher incidence of
malignant transformation. Lesions can be either superficial or deep, involving
small cutaneous nerves or large major nerve trunks. Superficial neurofibromas
are typically small painless masses, whereas deeper neurofibromas are commonly
associated with neurologic symptoms.
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Fig. 1B. —40-year-old woman with neurofibroma involving median nerve in
forearm. Coronal proton density—weighted fat-saturated MR image shows
fusiform shape of slightly heterogeneous high-signal-intensity lesion
(arrows) with proximal and distal "tails"
(arrowheads), representing "entering and exiting" median
nerve.
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Fig. 1C. —40-year-old woman with neurofibroma involving median nerve in
forearm. Axial fast spin-echo short tau inversion-recovery MR image shows
large well-defined predominantly high-signal-intensity lesion
(arrows) in median nerve distribution.
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Fig. 2B. —30-year-old man with neurofibroma involving right C3 cervical
nerve root. Axial T1-weighted gadolinium-enhanced MR image shows large
dumbbell-shaped enhancing lesion (open arrows) extending through
right C2-C3 neuroforamen (arrowheads).
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Fig. 3A. —18-year-old man with neurofibroma of common peroneal nerve
and clinical history of foot drop. Transverse sonogram (7-12—MHz linear
array transducer) of lateral leg just distal to knee reveals rounded
relatively hypoechoic lesion (solid arrows) with subtle central
region of increased echogenicity (open arrows), consistent with
sonographic "target" sign, which is better appreciated on
real-time imaging.
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Fig. 3B. —18-year-old man with neurofibroma of common peroneal nerve
and clinical history of foot drop. Axial fast spin-echo short tau
inversion-recovery MR image shows round lesion (arrow) with
high-signal-intensity periphery and low-signal-intensity central region,
corresponding to lesion seen in A. Lesion represents MR target
sign.
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Fig. 3C. —18-year-old man with neurofibroma of common peroneal nerve
and clinical history of foot drop. Axial T1-weighted MR image shows fatty
atrophy (arrows) of anterior compartment muscles (tibialis anterior,
extensor hallucis longus, and extensor digitorum longus), consistent with
peroneal nerve distribution.
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Pathologically, neurofibromas are intimately associated with the parent
nerve, growing in a longitudinal fusiform manner with the nerve
"entering and exiting" from the lesion. Neurofibromas are not
encapsulated. Surgical resection requires sacrificing the parent nerve because
the neurofibroma cannot be separated from the nerve fibers.
CT shows a well-defined mass that is hypodense relative to muscle and
enhances after contrast administration. Findings on MR imaging reveal
low-signal-intensity lesions on T1-weighted sequences, high-signal-intensity
lesions on T2-weighted sequences, and avid contrast enhancement (Figs.
1A,1B,1C
and
2A,2B).
Signal on T2-weighted images can be either homogeneously hyperintense or show
a characteristic target sign, consisting of a central hypointense region
[4] (Fig.
3A,3B,3C).
A dumb-bell-shape is characteristic for spinal nerve root neurofibromas, which
may enlarge the neuroforamen (Fig.
2A,2B).
Another typical feature is a fusiform shape oriented longitudinally in the
nerve distribution, often revealing tapered ends that are contiguous with the
parent nerve (Fig.
1A,1B,1C).
Sonography shows a well-defined hypoechoic lesion and may show distal acoustic
enhancement, simulating a cyst. A target sign can be seen in neurofibromas
with a hypoechoic peripheral zone and a hyperechoic central zone
[1] (Figs.
3A,3B,3C
and
4A,4B,4C,4D).
Identification of a lesion and associated muscle atrophy in a typical nerve
distribution may suggest a peripheral nerve sheath tumor
[3] (Fig.
3A,3B,3C).
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Fig. 4A. —19-year-old man with neurofibromatosis and extensive
plexiform neurofibromas. Coronal T2-weighted MR image of right knee
posteriorly reveals conglomerate multilobulated masses (white arrows)
representing plexiform neurofibromas. Individual lesions show high signal
intensity peripherally and low signal intensity centrally (black
arrows), consistent with MR "target" sign.
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Fig. 4B. —19-year-old man with neurofibromatosis and extensive
plexiform neurofibromas. Longitudinal extended field-of-view sonogram
(7.5-MHz—linear array transducer) of right lower extremity from
posterior approach shows extensive multilobulated masses (arrowheads)
extending entire length of leg in sciatic and tibial nerve distributions. Note
posterior femoral cortex and tibial cortices (arrows). K = knee.
(Reprinted with permission from
[1])
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Fig. 4C. —19-year-old man with neurofibromatosis and extensive
plexiform neurofibromas. Focused longitudinal sonogram
(5-MHz—curvilinear transducer) of posterior thigh shows large
conglomerated masses. Each lesion (arrows) reveals target sign.
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Fig. 4D. —19-year-old man with neurofibromatosis and extensive
plexiform neurofibromas. Longitudinal sonogram (7.5-MHz—linear array
transducer) of left elbow medially, distal to cubital tunnel, reveals solitary
ovoid mass (arrows) in contiguity with ulnar nerve
(arrowheads). Lesion shows hypoechoic echotexture, well-defined
margins, and subtle distal acoustic enhancement. (Reprinted with permission
from [1])
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Neurofibromatosis
Neurofibromatosis (Figs.
4A,4B,4C,4D,5A,5B,6A,6B),
also known as von Recklinghausen's disease, is a phakomatosis that displays a
wide spectrum of clinical expression with neurocutaneous abnormalities and
involvement of multiple organ systems. There are two major forms, designated
neurofibromatosis type 1 (NF 1) and neurofibromatosis type 2 (NF 2), which are
clinically and genetically distinct. NF 1 is commonly associated with
peripheral nerve sheath tumors, whereas NF 2 primarily affects the central
nervous system. NF 1 is among the most common genetically transmitted disease,
affecting one in 3000 births. It is autosomal dominantly inherited although up
to 50% of cases may evolve from a new mutation, with advanced paternal age as
a risk factor [2].
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Fig. 5A. —39-year-old man with neurofibromatosis and numerous localized
neurofibromas in pelvis and lower extremities. Coronal fast spin-echo short
tau inversion-recovery MR image of pelvis shows multiple ovoid homogeneous
high-signal-intensity lesions (arrows).
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Fig. 5B. —39-year-old man with neurofibromatosis and numerous localized
neurofibromas in pelvis and lower extremities. Coronal T1-weighted MR image of
knee reveals numerous ovoid homogeneous intermediate signal lesions
(arrows) in chainlike pattern in medial soft tissues, surrounded by
fat representing "split-fat" sign (arrowheads).
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Fig. 6A. —62-year-old man with neurofibromatosis and diffuse
neurofibromas involving superficial tissues of left lower extremity.
Anteroposterior ScoutView from CT scan shows marked enlargement of soft
tissues of left lower extremity (arrowheads) as compared with right
lower extremity, consistent with hemihypertrophy.
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Fig. 6B. —62-year-old man with neurofibromatosis and diffuse
neurofibromas involving superficial tissues of left lower extremity. CT scan
of left calf shows marked thickening and enlargement of superficial soft
tissues primarily posteriorly (curved arrows), which is heterogeneous
with mixed soft-tissue and fat attenuation. Muscle compartment (straight
arrows) is essentially uninvolved and normal. Percutaneous core biopsy
needle (arrowheads) was used to confirm diagnosis.
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Pathologically, neurofibromas in NF 1 can be divided into three types:
localized, plexiform, and diffuse
[2,
5]. Localized neurofibromas are
identical to solitary neurofibromas; however, in the setting of NF 1, they
tend to be larger, multiple, and, more commonly, deep in location. Plexiform
neurofibromas are pathognomonic for NF 1, usually involving a long segment of
a major nerve trunk and extending into the nerve branches, and they result in
the so-called "bag of worms" appearance on gross inspection and
cross-sectional imaging. Diffuse neurofibromas most commonly occur in children
and young adults and are typically localized to the subcutaneous tissues
[2,
5]. In view of the diffuse
involvement, patients are generally treated conservatively, with surgical
resection reserved for intolerable lesions.
CT of plexiform neurofibromas shows large multilobulated low-attenuation
masses, usually within a major nerve distribution. MR imaging reveals large
conglomerate masses consisting of innumerable neurofibromas, diffusely
thickening the involved nerve and often extending into nerve branches. Both
sonography and MR imaging may show the target sign
[1,
4] (Fig.
4A,4B,4C,4D).
Localized neurofibromas in neurofibromatosis are radiologically identical to
solitary neurofibromas, but multiple lesions are often present and may be seen
with plexiform neurofibromas (Figs.
4A,4B,4C,4D
and
5A,5B).
The split-fat sign represents a rim of fat surrounding the tumor, which
originates from the nerve in an intermuscular location (Fig.
5A,5B).
The diffuse form of neurofibroma is ill-defined and extensively reticulates
through the subcutaneous tissue
[5]. Severe thickening of the
subcutaneous tissues can result in marked enlargement of the affected
extremity (Fig.
6A,6B).
Schwannomas
Schwannomas (Figs.
7,8A,8B,8C,9A,9B),
also known as neurilemmomas, most frequently affect patients who are 20-40
years old and represent approximately 5% of benign soft-tissue neoplasms
[2,
3]. Most lesions are solitary
and present as a slowly growing painless soft-tissue mass. Symptoms are
unusual, unless the mass has become large enough to compress the adjacent
nerve. Infrequently, these tumors can be associated with NF 1, and in such
cases, they are invariably plexiform or multiple lesions.
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Fig. 7. —14-year-old girl with schwannoma involving ulnar nerve in
upper extremity. Sagittal T2-weighted MR image of right upper extremity shows
large ovoid lesion (arrowheads) eccentrically located in distribution
of ulnar nerve (white arrows). Lesion is predominantly high signal
intensity with low-signal-intensity central region (black arrows),
representing MR "target" sign.
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Fig. 8A. —37-year-old man with degenerating schwannoma of sacrum and
pelvis. Transverse sonogram (3.5-MHz—curvilinear transducer) of pelvis
from anterior approach shows large heterogeneous relatively hypoechoic lesion
(arrowheads) in presacral region. Note central anechoic areas
(arrows), consistent with cystic cavities.
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Fig. 8B. —37-year-old man with degenerating schwannoma of sacrum and
pelvis. CT scan of pelvis shows large soft-tissue mass (white
arrowheads) arising from left anterior sacrum (black arrowheads)
and displacing pelvic structures. Note central and peripheral fluid
attenuation areas (arrows), corresponding to cystic cavities seen on
sonogram (A).
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Fig. 8C. —37-year-old man with degenerating schwannoma of sacrum and
pelvis. Axial T2-weighted MR image shows pelvic lesion (black arrows)
with cystic cavities (arrowheads) and sacral origin (white
arrows) as seen on CT scan (B).
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Fig. 9A. —76-year-old man with "ancient" schwannoma of
sacrum and pelvis. CT-guided biopsy was performed in left lateral decubitus
position (image is rotated 90° counterclockwise) from posterior approach.
Large presacral lesion (white arrowheads) originating from sacrum
with extensive dystrophic calcifications (black arrowheads) primarily
in peripheral pattern is shown. Note core biopsy needle (arrows) with
tip in sacral mass.
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Fig. 9B. —76-year-old man with "ancient" schwannoma of
sacrum and pelvis. Proton density—weighted fat-saturated MR image shows
presacral lesion (white arrows) originating from sacrum
(arrowheads) and central cystic region with low-signal-intensity
focus (black arrow) in non-dependent location, representing gas
introduced at biopsy.
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Pathologically, schwannomas are fusiform masses that are eccentrically
located in relation to the involved nerve and are contained within a capsule,
the epineurium. They are composed primarily of Schwann's cells. Surgical
excision can usually spare the parent nerve because the schwannoma is
generally separable from the underlying nerve fibers.
Imaging findings of schwannomas are similar to those seen with
neurofibromas and, in many cases, cannot be distinguished. The fusiform shape,
split-fat sign, and target sign can be seen in either lesion. However, some
features can help differentiate these two lesions. When the parent nerve is
identified, an eccentrically positioned lesion (in relation to the nerve)
suggests a schwannoma (Fig.
7), whereas a centrally located mass suggests a neurofibroma (Fig.
1A,1B,1C).
Heterogeneous appearance with degeneration and cystic cavitation are much more
common in schwannomas than in neurofibromas (Fig.
8A,8B,8C).
"Ancient" schwannomas refer to long-standing lesions with advanced
degeneration exhibiting calcification, hyalinization, and cystic cavitation,
findings that can be identified on imaging
[6] (Fig.
9A,9B).
Malignant Peripheral Nerve Sheath Tumors
Malignant peripheral nerve sheath tumors (Figs.
10A,10B,10C,11A,11B,12A,12B,12C)
have also been referred to as malignant schwannomas, neurogenic sarcomas,
malignant neurilemmomas, and neurofibrosarcomas. They most frequently affect
patients who are 20-50 years old and represent 5-10% of soft-tissue sarcomas
[2,
3]. A high proportion of
malignant peripheral nerve sheath tumors (approximately 50%) occurs in
association with NF 1. On the other hand, only a small fraction of patients
with NF 1 (approximately 5%) develop malignant peripheral nerve sheath tumors
[2,
3,
7]. Malignant peripheral nerve
sheath tumors generally involve the major nerve trunks and present with pain
and neurologic symptoms, as well as a possible soft-tissue mass. Secondary
malignant peripheral nerve sheath tumors can arise from prior radiation
treatment, with a latency period of longer than 10 years
[2,
3]. Primary intraosseous origin
of malignant peripheral nerve sheath tumors is exceedingly rare, particularly
involving a long bone; such lesions most commonly arise from the mandible
[7,
8].
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Fig. 10A. —60-year-old man with malignant peripheral nerve sheath tumor
involving sciatic nerve. CT scan with IV contrast material and patient in
prone position shows right posterior thigh lesion (arrowheads), which
enhances heterogeneously, in sciatic nerve distribution. CT-guided biopsy was
performed from posterior approach; note core biopsy needle (arrow)
introduced percutaneously.
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Fig. 10B. —60-year-old man with malignant peripheral nerve sheath tumor
involving sciatic nerve. Axial T2-weighted fat-saturated MR image shows large
lesion (arrows) with marked heterogeneity and associated surrounding
edema.
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Fig. 10C. —60-year-old man with malignant peripheral nerve sheath tumor
involving sciatic nerve. Sagittal T1-weighted fat-saturated
gadolinium-enhanced MR image shows fusiform posterior thigh lesion
(arrow) and heterogeneous contrast enhancement.
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Fig. 11A. —35-year-old man with secondary malignant peripheral nerve
sheath tumor of right flank after radiation therapy for Wilms' tumor as child.
Coronal fast spin-echo short tau inversion-recovery MR image reveals large
lobulated high-signal-intensity mass (arrow) in right flank
superficially.
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Fig. 11B. —35-year-old man with secondary malignant peripheral nerve
sheath tumor of right flank after radiation therapy for Wilms' tumor as child.
Axial T1-weighted fat-saturated gadolinium-enhanced MR image reveals
heterogeneous enhancement of lesion (arrow) located primarily in
subcutaneous tissues. Absence of right kidney was consistent with prior
nephrectomy (not shown).
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Fig. 12A. —53-year-old man with malignant intraosseous peripheral nerve
sheath tumor of tibia. (Reprinted with permission from
[7]) Anteroposterior radiograph
shows large lobulated intraosseous lesion, which has extended into medial soft
tissues.
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Fig. 12B. —53-year-old man with malignant intraosseous peripheral nerve
sheath tumor of tibia. (Reprinted with permission from
[7]) Sagittal gradient-recalled
echo MR image shows intraosseous and soft-tissue components of lesion
(arrows) with homogeneous increased signal intensity.
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Fig. 12C. —53-year-old man with malignant intraosseous peripheral nerve
sheath tumor of tibia. (Reprinted with permission from
[7]) Gross pathologic specimen
shows lesion extending superficially with possible infiltration into
subcutaneous tissues.
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Pathologically, malignant peripheral nerve sheath tumors are usually large
fusiform masses, frequently with extensive central necrosis and hemorrhage.
Malignant peripheral nerve sheath tumors are usually high-grade sarcomas and
treatment typically involves a combination of surgical resection, adjuvant
chemotherapy, and radiotherapy. Local recurrence and metastatic disease are
common complications.
Although malignant and benign lesions cannot be reliably distinguished by
imaging criteria, certain findings should raise the suspicion of a malignant
tumor. Malignant peripheral nerve sheath tumors tend to be larger (>5 cm).
They may exhibit ill-defined margins suggesting infiltration of adjacent
tissues and associated edema
[3] (Fig.
10A,10B,10C).
Heterogeneity with central necrosis on cross-sectional imaging is common in
malignant lesions (Figs.
10A,10B,10C
and
11A,11B)
although benign lesions with degeneration can also have a heterogeneous
appearance (Figs.
8A,8B,8C
and
9A,9B).
Similarly, calcification, more commonly associated with malignant lesions, can
also be present in ancient schwannomas (Fig.
9A,9B).
Malignant peripheral nerve sheath tumors can arise within a previous radiation
field (Fig.
11A,11B).
Primary intraosseous malignant peripheral nerve sheath tumors show a lytic
osseous lesion with cortical destruction and soft-tissue extension.
T1-weighted MR images reveal low-to-intermediate signal intensity, and
T2-weighted MR images show high signal intensity in the lesion (Fig.
12A,12B,12C).
In general, radiologic findings are nonspecific; however, given an aggressive
osseous lesion in the setting of neurofibromatosis, radiologists should
consider an intraosseous malignant peripheral nerve sheath tumor
[7,
8].
In conclusion, knowledge and recognition of the characteristic signs for
peripheral nerve sheath tumors can aid in the proper diagnosis and treatment
of these lesions.
Acknowledgments
We thank Curtis W. Hayes and N. Reed Dunnick for their contributions of
cases to our article.
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P.-L. Khong, W. H. S. Goh, V. C. N. Wong, C.-W. Fung, and G.-C. Ooi
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H. Pham, D. P. Fessell, J. E. Femino, S. Sharp, J. A. Jacobson, and C. W. Hayes
Sonography and MR Imaging of Selected Benign Masses in the Ankle and Foot
Am. J. Roentgenol.,
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S. Peer, P. Kovacs, C. Harpf, and G. Bodner
High-Resolution Sonography of Lower Extremity Peripheral Nerves: Anatomic Correlation and Spectrum of Disease
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[Abstract]
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Top
Introduction
Neurofibromas
