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Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of

frequency, multiplicity, and variety

Article  in  American Journal of Roentgenology · November 1995

DOI: 10.2214/ajr.165.4.7676998 · Source: PubMed

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Victor Felix Mautner Marcos Tatagiba

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 951

Spinal Tumors in Patients with

Neurofibromatosis Type 2: MR
Imaging Study of Frequency, Multiplicity,
and Variety

Victor-Felix Mautner1 OBJECTIVE. Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder
Marcos Tatagiba2 leading to various tumors of the CNS, with vestibular schwannomas being the hail-
Matthias Lindenau1 mark of the disease. We have observed multiple asymptomatic spinal lesions in
patients who have a single symptomatic spinal tumor. Accordingly, we studied the
Carsten F#{252}nsterer3
frequency, multiplicity, and variety of spinal tumors in all patients with NF2 to deter-
Stefan M. Pulst4 mine what is characteristic of the disease.
Lan Kluwe5
SUBJECTS AND METHODS. MR images of the entire spinal canal were made in 73
Friedhelm E. Zanella6 patients aged 4-69 years with NF2. The number, location, morphology, signal charac-
teristics, 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 two 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 two 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
Received January 3, 1995; accepted after revi-
sion May 8, 1995. multiple and of various histologic types. The presence of multiple and different patho-
logic types of spinal tumors is highly suggestive of NF2.
Supported by Hamburger Stiftung zur
Forderung der Krebsbek#{228}mpfung(No. 116, 127)
and the Wilhelm-Sander-Stiftung (93.05.21). AJR 1995;165:951-955
1Department of Neurology. Allgemeines Kran-
kenhaus Hamburg Ochsenzoll, Langenhorner
Chaussee 560, 22419 Hamburg, Germany. Ad- Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder with an
dress correspondence to V-F. Mautner. incidence of 1 :37,000 [1]. Its hallmark is the presence of bilateral vestibulan schwan-
2 Department of Neurosurgery, Nordstadtkran-
kenhaus Hannover, Haltenhoffstr. 41 , 30167 Ha-
nomas. Additional
peripheral
manifestations
nerve tumors, and cataracts
include spinal tumors as well as brain tumors,
[2]. The detection of multiple asymptomatic
nover, Germany.
3 Hamburg-Othmarschen MRI Institute, Othmar-
spinal lesions in patients with a symptomatic spinal tumor led to the assumption that
scher Kirchenweg 166, 22763 Hamburg. Germany. spinal tumors are more common in patients with NF2 than has been assumed [3].
4Neurogenetics Laboratory and Division of Confirmation of a high frequency of spinal tumors would show that such tumors are
Neurology, Cedars-Sinai Medical Center, Universi- a criterion of the disease and aid in the diagnosis in family members and sporadic
ty of California at Los Angeles, 8700 Beverly Hills
cases with suggested NF2. In order to determine the frequency, multiplicity, and van-
Blvd., Los Angeles, CA 90048.
ety of spinal lesions in NF2, we analyzed spinal MR images of 73 patients with NF2.
5Laboratory for Brain Tumor Biology, Neurosur-
gical Department, Universit#{228}tskrankenhaus Ep-
pendorf, Martinistr. 52, 20246 Hamburg. Germany.
Subjects and Methods
6Neuroradiology Department, Universit#{228}tsklini-
kum Essen, Hufelandstr. 55, 45122 Essen, Germany. Patients with NF2 were contacted through patient workshops and publications and
0361-803X/95/1654-951 through a neurofibromatosis treatment center. Additionally, some major neurosurgical
© American Roentgen Ray Society departments were contacted in search of patients with this disease.
952 MAUTNER ET AL. AJR:165, October 1995

The entire spinal canal of 73 patients (38 male, 35 female, 4-69 Nineteen of the patients who became clinically symptomatic had
years old) with a confirmed diagnosis of NF2 was examined by MR a total of 22 operations; the histologic examination of these tumors
imaging, and the resulting images were analyzed. In 68 patients, allowed an analysis of their specific histologic type.
NF2 was diagnosed in accordance with the 1991 National Institutes
of Health (NIH) criteria, according to which NF2 may be diagnosed
Results
when either bilateral 8th-nerve masses (seen by contrast-enhanced
MR imaging) are present or when there is a first-degree relative with MR imaging revealed spinal tumors in 65 (89%) of the 73
NF2 and either a unilateral 8th-nerve mass or a neurofibroma, men- patients we examined. On the basis of our MR imaging cnite-
ingioma, glioma, schwannoma, or posterior capsular cataract or na, 60 patients (82%) were found to have tumors (with 19
opacity at a young age [4]. The remaining five patients, who did not tumors of 16 patients pathologically proven and the tumors of
meet the NIH criteria, were given the diagnosis of NF2 after the per- 44 patients unproven) that were classified as extradural and
formance of mutation analysis or segregation analysis [5]. intradural extramedullary and could be either meningiomas
The radiologic diagnosis was based on the location of the tumor
(Fig. 1), schwannomas, or neurofibromas (Figs. 2A and 2B).
(cervical, thoracic, or lumbar spine), intramedullary or extramedullary
Of 24 patients (33%) with intramedullary tumors, 1 5 (21%)
position, age and sex of the patient, and previous radiologic and neuro-
were thought to have astrocytomas (Figs. 3A and 3B; with
logic findings. We classified tumors only in general terms as extradural
and intradural extramedullary tumors (meningiomas. schwannomas, none pathologically proven), three (4%) had ependymomas
and neurofibromas) and intramedullary tumors (astrocytomas, ependy- (Figs. 4A and 4B; with all pathologically confirmed), and
momas, or unknown because of uncertainty of morphologic criteria). To eight (11%) were thought to have unclassifiable intramedul-
exclude nonspecific findings. only tumors greater than 0.4 cm in diame- lary tumors (Fig. 5, Table 1 ; with none pathologically proven).
ter were considered. We regarded five or more tumors in any part of the
spine (cervical, thoracic, or lumbar region) as multiple tumors. In a
pathologic study, Russel and Rubinstein [6] noted several cases in
which one or even two spinal tumors were found in patients with no evi-
dence of neurofibromatosis. To differentiate from such cases, we
defined multiplicity as the occurrence of more than four spinal 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 coronal 4-mm slices were examined. Ti- and T2-
weighted sagittal images were obtained. Images with an echo time
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 prepared before and after IV administration of 0.1
mmol/kg or 0.2 mI/kg of gadopentetate dimeglumine. The cervical
images were obtained with a Helmholtz neck coil, and the thoracic
and lumbar images, with a circularly polarized surface coil.
All MR images were independently assessed by two radiologists. Fig. 1.-Histopathologicaliy proven meningiomas. 18-year-old man with
Tumors were assessed for their number, location, morphology, and pain radiating into right arm and diminished biceps jerk. Ti -weighted coro-
nal MR image (SE 500/iS [TRITE]) shows two nodular extramedullary intra-
signal characteristics on the Ti - and T2-weighted images and for durally located tumors with foraminal involvement in C4-C5. Symptomatic
signal behavior before and after administration of contrast medium. spinal meningiomas at young age suggest neurofibromatosis type 2.

Fig. 2.-Histopathologicaiiy proven neurofibro-

ma. 4-year-old boy presenting with tetraparesis.
A, Ti-weighted sagittai MR image (SE 500/15
[TR/TE]) shows multinodular extramedullary tu-
mor at C5-C6 compressing spinal cord. Variety
of spinal tumors in neurofibromatosis type 2 in-
ciudes neurofibromas.
B, Ti-weighted axial image confirms cx-
trameduilary location of tumor (600/i 9).
AJR:165, October 1995 MR IMAGING OF NEUROFIBROMATOSIS SPINAL TUMORS 953

Fig. 3.-Presumed astrocytomas. 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 con-
trast-enhancing tumors up to upper thoracic
spine. Multiple Intramedullary tumors are tea-
ture of neurofibromatosis type 2.

Fig. 4.-Histopathoiogically proven ependy-

moma. 42-year-old woman with intractable neck
pain.
A, Ti-weighted sagittal MR image (SE 500/15
[TR/TE]) after administration of contrast materi-
al 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 (gradi-
ent-recalied echo 340/18, 18 flip angle) shows
clear demarcation of nodular Intramedullary tu-
mor. Cranially and caudally, caplike black he-
mosiderin borders are visible.

TABLE i : Types of Tumors Found in 73 Patients with Neurofi-

bromatosis Type 2

No. of Patients with Spinal Tumors

Type of Tumor Location in Spine

All Regionsa
Cervical Thoracic Lumbar

Intradural and extra- 60 (82%) 36 40 49

dural extramedullary
tumors
Intramedullary tumors
Unknown 8(11%) 6 4 0
Ependymoma/ 3(4%) 2 1 0
astrocytoma b
Astrocytomal i5(2i#{176}’o) ii 7 1
ependymomac
Syrinx 2(3%) 0 2 0
No tumor 8(11#{176}/o) 26 25 24
Fig. 5.-Intramedullary lesion of unknown type, no histopathologic proof.
29-year-old man, clinically asymptomatic. Fast spin echo T2-weighted (3500/ aSums do not add up to 100#{176}o
because multiple tumors may occur in one
91 [TR/TE]) sagittal MR Image of upper thoracic spine shows long extended
hyperintense intramedullary tumor with nodular structure (small amount of patient.
bNo clear neuroradiologic diagnosis. most likely ependymoma.
contrast enhancement in solid central parts of tumor is not shown here). In-
tramedullary tumors of unknown classification are part of variety in our series. cNo clear neuroradiologic diagnosis. most likely astrocytoma.
954 MAUTNER ET AL. AJR:165, October 1995

Extra- and intramedullany tumors were not localized to any tumors has not been elucidated so far in a larger series of
part of the spine. Thus, 47 patients (64%) were found to have patients with NF2.
at least one tumor in the cervical spine, 48 (66%) to have at Cumran et al. [12] documented a high frequency (26%) of
least one tumor in the thomacic spine, and 49 (67%) to have spinal intramedullary tumors in a kindred of 23 family mem-
at least one tumor in the lumbar spine.
Twenty-four (33%) of the 73 patients were found to have
intramedullary tumors. In the cervical part of the cord, 11
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 syningohydmo-
myelia (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 Fig. 6.-Multiple extramedullary tumors, no histopathologic proof. 28-
spine (double counting possible). Two patients (3%) had mul- year-old man, clinically asymptomatic. Ti-weighted (500/15 [TRITE]) con-
trast-enhanced MR image shows multiple evenly and intensely contrast-
tiple tumors in total, but not in any specific part of the spine.
enhanced intraspinal extramedullary tumors. Multiplicity of extramedul-
Twenty-two patients (30%) had less than five tumors in total lary tumors in one part of spinal canal is significant finding in neurofibro-
and eight patients (11%) had no tumors. Twenty-two (30%) of matosis type 2.

the 73 patients had clinically symptomatic tumors. Sixteen of

these patients subsequently had an operation, and three had
TABLE 2: Histologic Findings of 22 Tumors Removed in 19 Pa-
two operations (22 operations in all). The histologic examina-
tients with Neurofibromatosis Type 2
tion showed three tumors to be ependymomas (Figs. 7A and
7B), seven to be meningiomas, ten to be schwannomas, and No. of Tumors
two to be neurofibmomas (Table 2). The three patients with
Type of Tumor All Location in Spine
clinically symptomatic tumors who did not have surgery were
Regions
thought to have astrocytomas. Cervical Thoracic Lumbar

Intradural and extradural

Discussion extramedullary tumors

Neumopathologic studies of cases with bilateral acoustic Schwannomas 10 2 3 5

Meningiomas 7 3 4 -
schwannoma revealed the association between the multiplic-
Neurofibromas 2 2 - -
ity of cranial and spinal meningeal, nerve sheath, and glial
Intramedullary tumors
neoplasms and spinal tumors [7-11]. However, the signifi-
Ependymomas 3 2 1 -

cance of the frequency, multiplicity, and variety of spinal

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-en-
hanced MR image shows intensely enhanced tu-
mor node 7 mm in size in region of medulla
oblongata after operation on histopathologically
proven ependymoma near craniocervical transi-
tion. The variety of spinal tumors in neurofibro-
matosis type 2 not only relates to histopathologic
type but also to different age groups, especially
children. The multiplicity of spinal tumors in neu-
rofibromatosis type 2 may also relate to appear-
ance of metastases in ependymoma.
B, Ti -weighted (600/20) contrast-enhanced
MR image shows multiple small contrast-en-
hancing tumor nodules in area of cauda equina.
Suspected relapse of ependymoma with drop
metastases. No histopathologic proof.
 AJR:165, October 1995 MR IMAGING OF NEUROFIBROMATOSIS SPINAL TUMORS 955

bems affected by NF2. In a population-based study involving Conclusion

only partial examination ofthe spine in symptomatic patients, Spinal tumors occurring at a high frequency, multiplicity,
spinal tumors were found in 26% of the patients [13]. In a and variety are a characteristic feature of NF2 and occur in
recent study by Parry et aI. [14], MR imaging of the entire
symptomatic as well as in asymptomatic patients. The pmes-
spine was performed in 40 of 49 patients with NF2 and
ence of multiple and different intraspinal tumors suggests
revealed spinal tumors in 30 patients (75%). Our MR imaging NF2. The detection of spinal tumors in cases that do not sat-
study confirms these observations in that 65 of 73 NF2 isfy the diagnostic criteria for NF2 may allow the diagnosis in
patients were found to have spinal tumors.
at-risk family members and sporadic cases and thus permit
Our results have some limitations, because our study was
appropriate genetic counseling.
not population-based. Even assuming a referral bias, how-
ever, the finding that the proportion of patients with spinal
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