in 73 patients aged 4-69 years with NF2. The number, location, morphology, signal charac- teristics, and contrast medium uptake of the spinal tumors as seen.
951
Spinal Tumors Neurofibromatosis Imaging Study and Variety
Victor-Felix Mautner1 Marcos Tatagiba2 Matthias Lindenau1 Carsten F#{252}nsterer3 Stefan M. Pulst4 Lan Kluwe5 Friedhelm E. Zanella6
in Patients with Type 2: MR
of Frequency,
Multiplicity,
OBJECTIVE. Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder leading to various tumors of the CNS, with vestibular schwannomas being the hailmark of the disease. We have observed multiple asymptomatic spinal lesions in patients who have a single symptomatic spinal tumor. Accordingly, we studied the frequency, multiplicity, and variety of spinal tumors in all patients with NF2 to determine what is characteristic of the disease. SUBJECTS AND METHODS. MR images of the entire spinal canal were made in 73 patients aged 4-69 years with NF2. The number, location, morphology, signal characteristics, and contrast medium uptake of the spinal tumors as seen on MR images were recorded and analyzed. Histopathologic proof of 22 spinal tumors was obtained in 1 9 patients. RESULTS. Spinal tumors were found on MR images in 89% of the patients studied. No location in any part of the spine was preferred. MR imaging showed intramedullary tumors in 24 patients (33%) (three ependymomas pathologically proven). Extradural and intradural extramedullary tumors were found on MR imaging in the cervical spine of 36 patients, the thoracic spine of 40 patients, and the lumbar spine of 49 patients. These tumors were meningiomas, schwannomas, or neurofibromas, three categories that could not be differentiated on the basis of the neuroradiologic findings, with ten schwannomas, seven meningiomas, and neurofibromas pathologically proven. Extradural extramedullary tumors were found on MR imaging in the cervical spine of 1 2 patients, the thoracic spine of five patients, and the lumbar spine of 1 8 patients. A syrinx associated with a tumor was found in patients. in 19 patients the variety of tumor types was confirmed by histologic examination. CONCLUSION. Patients with NF2 frequently have spinal tumors, which are often multiple and of various histologic types. The presence of multiple and different pathologic types of spinal tumors is highly suggestive of NF2.
two
two
Received January 3, 1995; accepted
after
revi-
sion May 8, 1995.
Supported by Hamburger Stiftung zur Forderung der Krebsbek#{228}mpfung(No. 116, 127) and the Wilhelm-Sander-Stiftung (93.05.21). 1Department
of Neurology.
Allgemeines
kenhaus Hamburg Ochsenzoll, Langenhorner Chaussee 560, 22419 Hamburg, Germany. Address correspondence to V-F. Mautner. 2
Department
kenhaus
of Neurosurgery,
Hannover,
Haltenhoffstr.
Nordstadtkran41
,
30167
Ha-
nover, Germany. 3 Hamburg-Othmarschen MRI Institute, Othmarscher Kirchenweg 166, 22763 Hamburg. Germany.
4Neurogenetics
Laboratory
and
Division
of
Neurology, Cedars-Sinai Medical Center, University of California at Los Angeles, 8700 Beverly Hills
Blvd., Los Angeles, CA 90048. 5Laboratory for Brain Tumor Biology, Neurosurgical Department, Universit#{228}tskrankenhaus Eppendorf, Martinistr. 52, 20246 Hamburg. Germany.
6Neuroradiology kum Essen,
Hufelandstr.
0361-803X/95/1654-951 © American Roentgen
Department, 55, 45122 Ray Society
Universit#{228}tskliniEssen,
AJR
1995;165:951-955
Kran-
Germany.
Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder with an incidence of 1 :37,000 [1]. Its hallmark is the presence of bilateral vestibulan schwannomas. Additional manifestations include spinal tumors as well as brain tumors, peripheral nerve tumors, and cataracts [2]. The detection of multiple asymptomatic spinal lesions in patients with a symptomatic spinal tumor led to the assumption that spinal tumors are more common in patients with NF2 than has been assumed [3]. Confirmation of a high frequency of spinal tumors would show that such tumors are a criterion of the disease and aid in the diagnosis in family members and sporadic cases with suggested NF2. In order to determine the frequency, multiplicity, and vanety of spinal lesions in NF2, we analyzed spinal MR images of 73 patients with NF2.
Subjects
and
Methods
Patients with NF2 were through a neurofibromatosis
contacted treatment
departments
in search of patients with this disease.
were contacted
through patient workshops and publications and center. Additionally, some major neurosurgical
MAUTNER
952
The entire
spinal
canal
of 73 patients
years old) with a confirmed
diagnosis
imaging,
images
and
the
resulting
(38 male,
4-69 by MR
35 female,
of NF2 was examined were
analyzed.
In 68
patients,
are present or when there is a first-degree
at a young
age
[4]. The
remaining
five
relative with
patients,
who
did
not
meet the NIH criteria, were given the diagnosis of NF2 after the performance of mutation analysis or segregation analysis [5]. The radiologic diagnosis was based on the location of the tumor
(cervical,
thoracic,
position, logic
age
or lumbar spine), intramedullary
and
findings.
sex of the patient,
We
classified
tumors
and
previous
only
in general
or extramedullary radiologic
and
terms
of the
an analysis
na,
60
patients
tumors
44 patients intradural (Fig.
neuro-
as extradural
findings. only tumors greater than 0.4 cm in diameWe regarded five or more tumors in any part of the
which
dence defined
thoracic,
study,
one
or
Russel
or even
two
lumbar
and
spinal
tumors
of neurofibromatosis. multiplicity
region)
as
Rubinstein were
found
To differentiate
as the occurrence
multiple
[6] noted
in patients
from
of more
tumors.
several
than
with
histologic
had
of these
tumors
type.
(82%)
unproven)
were
found
to have
pathologically
proven
that were
extramedullary
and
classified could
be
or neurofibromas
tumors and
(with
19
the tumors
as extradural
of
and
either
meningiomas
(Figs.
2A and
2B).
none
pathologically
(Figs.
4A and 4B; with (11%) were thought (Fig.
proven),
5, Table
three
(4%)
had
ependymomas
all pathologically confirmed), and to have unclassifiable intramedul1 ; with
none
pathologically
proven).
in
no evi-
cases,
spinal
symptomatic
In a
cases
such four
clinically
examination
Of 24 patients (33%) with intramedullary tumors, 1 5 (21%) were thought to have astrocytomas (Figs. 3A and 3B; with
lary tumors
(cervical,
became
specific
1), schwannomas,
eight
pathologic
of their
of 16 patients
exclude nonspecific spine
who
the histologic
1995
MR imaging revealed spinal tumors in 65 (89%) of the 73 patients we examined. On the basis of our MR imaging cnite-
and intradural extramedullary tumors (meningiomas. schwannomas, and neurofibromas) and intramedullary tumors (astrocytomas, ependymomas, or unknown because of uncertainty of morphologic criteria). To ter were considered.
patients
of 22 operations;
October
Results
NF2 and either a unilateral 8th-nerve mass or a neurofibroma, meningioma, glioma, schwannoma, or posterior capsular cataract or opacity
AJR:165,
Nineteen
a total allowed
NF2 was diagnosed in accordance with the 1991 National Institutes of Health (NIH) criteria, according to which NF2 may be diagnosed when either bilateral 8th-nerve masses (seen by contrast-enhanced
MR imaging)
ET AL.
we
tumors.
(Note that the occurrence of various types of tumor at various locations results in percentages that do not add up to 100.) The examinations were performed between January 1991 and November 1994 using a 1.5-T Siemens Magnetom 63 SP scanner. Sagittal
and
weighted
coronal
sagittal
4-mm
images
slices
were
were
examined.
obtained.
Images
Tiwith
an
and echo
T2time
of 1 5-25 msec and a repetition time of up to 600 msec were regarded as Ti-weighted, and those with an echo time of between 80 and 120 msec and a repetition time of more than 2000 msec were regarded as T2-weighted. Ti-weighted coronal and sagittal images
were
mmol/kg images
prepared
or 0.2 were
and lumbar All MR
before
mI/kg
obtained
images, images
and
of gadopentetate with
a Helmholtz
with a circularly were
independently
after
IV
administration
dimeglumine. neck
polarized
coil,
assessed
behavior
before
and
after
administration
0.1
cervical
the
thoracic
coil.
by two
Tumors were assessed for their number, location, signal characteristics on the Ti - and T2-weighted signal
and
surface
of The
radiologists.
morphology, and images and for
of contrast
medium.
Fig. 1.-Histopathologicaliy proven meningiomas. 18-year-old man with pain radiating into right arm and diminished biceps jerk. Ti -weighted coronal MR image (SE 500/iS [TRITE]) shows two nodular extramedullary intradurally located tumors with foraminal involvement in C4-C5. Symptomatic spinal meningiomas at young age suggest neurofibromatosis type 2.
Fig. 2.-Histopathologicaiiy proven neurofibroma. 4-year-old boy presenting with tetraparesis. A, Ti-weighted sagittai MR image (SE 500/15 [TR/TE]) shows multinodular extramedullary tumor at C5-C6 compressing spinal cord. Variety of spinal tumors in neurofibromatosis type 2 inciudes neurofibromas. B, Ti-weighted axial image confirms cx-
trameduilary
location
of tumor (600/i 9).
AJR:165,
October
MR IMAGING
1995
Fig. 3.-Presumed
astrocytomas.
OF NEUROFIBROMATOSIS
SPINAL
TUMORS
953
31-year-
old woman with atactic gait disturbance. A, Ti-weighted coronal MR image(5E 500/15 [TR/TE]) shows three intramedullary masses
with intense
contrast
enhancement
centrally
and diffuse contrast enhancement peripherally. B, Ti-weighted sagittal MR Image (SE 500/ i5) confirms intrameduilary localization of contrast-enhancing tumors up to upper thoracic spine. Multiple Intramedullary tumors are teature of neurofibromatosis type 2.
Fig. 4.-Histopathoiogically
moma. 42-year-old pain.
proven
ependy-
woman with intractable
neck
A, Ti-weighted sagittal MR image (SE 500/15 [TR/TE]) after administration of contrast material shows intrameduilary tumor reaching from Ci to C4 with peripheral contrast enhancement and cystic tumor area reaching medulla oblon-
gata. Spinal ependymomas
belong to spectrum
of neurofibromatosis type 2. B, Flash two-dimensional MR image ent-recalied echo 340/18, 18 flip angle)
clear demarcation
(gradishows
of nodular Intramedullary
mor. Cranially and caudally, caplike mosiderin borders are visible.
black
tuhe-
TABLE i : Types bromatosis Type
of Tumors 2
Found
in 73 Patients
No. of Patients Type
with Neurofi-
with Spinal
of Tumor
Location
Tumors in Spine
All Regionsa
Intradural and extradural extramedullary tumors Intramedullary tumors Unknown Ependymoma/ astrocytoma
Fig. 5.-Intramedullary lesion of unknown type, no histopathologic 29-year-old man, clinically asymptomatic. Fast spin echo T2-weighted 91 [TR/TE])
sagittal
MR Image
of upper
thoracic
spine
shows
proof. (3500/ long extended
hyperintense intramedullary tumor with nodular structure (small amount of contrast enhancement in solid central parts of tumor is not shown here). Intramedullary tumors of unknown classification are part of variety in our series.
Thoracic
Lumbar
36
40
49
6 2
4 1
0 0
7
1
2 25
0 24
8(11%) 3(4%)
b
Astrocytomal ependymomac Syrinx No tumor aSums
60 (82%)
Cervical
i5(2i#{176}’o)
ii
2(3%) 8(11#{176}/o)
do not add up to 100#{176}o because
patient. bNo clear neuroradiologic cNo clear neuroradiologic
diagnosis. diagnosis.
0 26 multiple
tumors
may occur
most likely ependymoma. most likely astrocytoma.
in one
954
MAUTNER
Extra- and intramedullany tumors were not localized part of the spine. Thus, 47 patients (64%) were found at least one tumor in the cervical spine, 48 (66%) to least one tumor in the thomacic spine, and 49 (67%) at least one tumor in the lumbar spine. Twenty-four (33%) of the 73 patients were found intramedullary
tumors.
In the
cervical
part
of the
to any to have have at to have
operations
tion
showed
(22 operations three
tumors
in all). The to be ependymomas
histologic
tumors patients
AJR:165,
has not been with NF2.
Cumran
spinal
et al. [12]
elucidated
so far in a larger
series
of
a high frequency (26%) of in a kindred of 23 family mem-
documented
intramedullary
October 1995
tumors
11
examina-
(Figs.
seven to be meningiomas, ten to be schwannomas, two to be neurofibmomas (Table 2). The three patients clinically symptomatic tumors who did not have surgery thought to have astrocytomas. 7B),
AL.
to have cord,
patients were thought to have astrocytomas, six to have tumors that were unclassifiable on the basis of MR imaging criteria, and two to have ependymomas. The corresponding figures for the thoracic part of the cord were seven, four, and one, whereas in the conus medullamis one patient was thought to have an astrocytoma. In the case of two patients, an intramedullary tumor was accompanied by syningohydmomyelia (Table 1). Extramedullary tumors were found in the cervical spine in 36 patients, in the thoracic spine in 40 patients, and in the lumbar spine in 49 patients. Of these, extradunal tumors were found in the cervical spine in 12 patients, in the thoracic spine in five patients, and in the lumbar spine in 18 patients. Multiplicity of tumors was found in 41 patients (56%). Of these patients, 15 showed multiple tumors in the cervical spine (Fig. 6), 17 in the thoracic spine, and 37 in the lumbar spine (double counting possible). Two patients (3%) had multiple tumors in total, but not in any specific part of the spine. Twenty-two patients (30%) had less than five tumors in total and eight patients (11%) had no tumors. Twenty-two (30%) of the 73 patients had clinically symptomatic tumors. Sixteen of these patients subsequently had an operation, and three had two
ET
7A and
and with were
Fig. 6.-Multiple trast-enhanced
enhanced
Neumopathologic studies of cases with bilateral acoustic schwannoma revealed the association between the multiplicity of cranial and spinal meningeal, nerve sheath, and glial neoplasms and spinal tumors [7-11]. However, the significance of the frequency, multiplicity, and variety of spinal
MR image
intraspinal
tumors,
shows
evenly
proof.
and intensely
is significant
of 22 Tumors Type 2
28-
(500/15 [TRITE]) con-
tumors. Multiplicity
canal
TABLE 2: Histologic Findings tients with Neurofibromatosis
no histopathologic
Ti-weighted
multiple
extramedullary
lary tumors in one part of spinal matosis type 2.
contrast-
of extramedul-
finding
in neurofibro-
Removed
in 19 Pa-
No. of Tumors Type of Tumor
Location
All Regions
Intradural Discussion
extramedullary
year-old man, clinically asymptomatic.
in Spine
Cervical
Thoracic
10 7 2
2 3 2
3 4
3
2
Lumbar
and extradural
extramedullary
tumors
Schwannomas Meningiomas Neurofibromas Intramedullary
Ependymomas
5 -
-
-
tumors
1
-
Fig. 7.-Histologically proven ependymoma. 1 6-year-old boy with presenting symptom of tetraparesis at age of 10 years. A, Ti-weighted (680/25 [TR1TE]) contrast-enhanced MR image shows intensely enhanced tumor node 7 mm in size in region of medulla oblongata after operation on histopathologically proven ependymoma near craniocervical transition. The variety of spinal tumors in neurofibromatosis type 2 not only relates to histopathologic type but also to different age groups, especially children. The multiplicity of spinal tumors in neurofibromatosis type 2 may also relate to appearance of metastases in ependymoma. B, Ti -weighted (600/20) contrast-enhanced MR image shows multiple small contrast-enhancing tumor nodules in area of cauda equina. Suspected relapse of ependymoma with drop
metastases.
No histopathologic
proof.
MR IMAGING
AJR:165, October 1995
OF NEUROFIBROMATOSIS
SPINAL
TUMORS
955
bems affected by NF2. In a population-based study involving only partial examination ofthe spine in symptomatic patients, spinal tumors were found in 26% of the patients [13]. In a recent study by Parry et aI. [14], MR imaging of the entire spine was performed in 40 of 49 patients with NF2 and revealed spinal tumors in 30 patients (75%). Our MR imaging study confirms these observations in that 65 of 73 NF2 patients were found to have spinal tumors. Our results have some limitations, because our study was not population-based. Even assuming a referral bias, however, the finding that the proportion of patients with spinal tumors-especially with multiple tumors-is so high is clinically relevant in a number of ways. The frequency of spinal tumors in our study is similar to that of acoustic schwannomas in other studies (92% in Parry et al. [14]; 85% in Evans et al. [13]). The diagnostic value of spinal tumors for NF2 is thus similar to that of acoustic schwannomas and distinctly superior to that of some of the NIH diagnostic criteria, such as cataract or schwannomas of the skin on cranial nerves. Multiple spinal tumors should therefore be regarded as a hallmark of the disease [3]. The high frequency of spinal tumors in every part of the spine and the fact that we found no preferred localization of tumors in any part of the spine underscores the need to scan all parts of the spine in asymptomatic at-risk family membems. The occurrence of spinal tumors in different parts of the spine (22, on 30%, of our patients had less than five tumors in total) should immediately suggestthe differential diagnosis of NF2 besides familial meningioma [15], schwannomatosis [16], NFl [1 7], on metastatic dissemination in the CSF. A characteristic feature of the disease is the multiplicity of tumors in the spine. Parry et al. [14] found a mean number of 8.7 spinal tumors. However, this estimate was minimal, because tumors in some areas were too numerous to count. Our investigation confirmed the multiplicity of spinal tumors in 56% of the patients studied, with a predominance in the lumbar region (37%). In 15% of the patients with NF2 that Evans et al. studied, no vestibulam schwannomas were found, and at the time of the
Conclusion
screening,
13. Evans DGR, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. 0 J Med 1992:304:603-618
11%
of the
patients
were
found
to
be
clinically
asymptomatic [1 3]. Sporadic cases comprise one third to one half of NF2 patients [1], and segregation and direct mutation analysis is not effective in all patients [18, 19]. For this latter group of patients, MR imaging of the spine can identify NF2. MR imaging of the spine may also be particularly worthwhile in patients found to have a unilateral vestibulam schwannoma and multiple meningiomas on schwannomas of the other cranial nerves on the skin [20]. In such cases, MR imaging helps to confirm the provisional diagnosis of NF2 and thus permits appropriate genetic counseling of patients. In 22 histopathologically proven spinal tumors, schwannomas and meningiomas were the most common tumor types. Ependymomas, astrocytomas, and neumofibromas seem to be less common. This variety of tumor types seen in patients with NF2 is also characteristic of the disease.
The reader’s
attention
is directed
to the commentary
Spinal tumors occurring at a high frequency, multiplicity, and variety are a characteristic feature of NF2 and occur in symptomatic as well as in asymptomatic patients. The pmesence of multiple and different intraspinal tumors suggests NF2. The detection of spinal tumors in cases that do not satisfy the diagnostic criteria for NF2 may allow the diagnosis in at-risk family members and sporadic cases and thus permit appropriate genetic counseling.
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which
appears
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