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DOI: 10.3171/2010.9.


Multifocal intradural extramedullary ependymoma

Case report

Eduardo Augusto Iunes, M.D.,1 João Norberto Stávale, M.D., Ph.D., 2

Rita de Cássia Caldas Pessoa, M.D., 3 Ricardo Ansai, M.D.,1 Franz Jooji Onishi, M.D.,1
Manoel Antonio de Paiva Neto, M.D., Ph.D.,1 Antônio de Pádua Bonatelli, M.D., Ph.D.,1
Sérgio Cavalheiro, M.D., Ph.D.,1 and Suzana M. Fleury Malheiros, M.D., Ph.D.1
Departments of 1Neurology and Neurosurgery, 2Pathology, and 3Radiology, Universidade Federal de São
Paulo, Brazil

In this paper, the authors present the case of a patient with multifocal intradural extramedullary ependymoma,
and they review 18 previously reported cases.
A 32-year-old man presented to the authors’ institution with a 1-month history of partial medullary syndrome.
Magnetic resonance imaging of the neuraxis revealed multifocal intradural extramedullary lesions at the bulbomed­
ullary junction and C2–3, T5–11, L-2, L-4, L-5, and sacrum. Histological examination revealed a WHO Grade II
The literature survey yielded 18 cases of ependymoma at the same location; none of them were multifocal at
presentation. The authors analyzed the epidemiological, clinical, and surgical features of all 19 cases reported to date,
including the present case.
Patients’ ages ranged from 24 to 69 years; 15 patients were women and 4 were men. The time elapsed from
symptom onset to diagnosis ranged from 1 month to 8 years. Pain (in 13 patients) and medullary syndrome (in 12)
were reported as the initial symptoms (information was not provided for 1 patient). Tumors were predominantly
located in the thoracic spine (11), but they also occurred in the cervicothoracic (3), cervical (2), and lumbar (2)
spine. The remaining tumor was multifocal. Solitary extramedullary tumors were found intraoperatively in 13 pa­
tients; 3 were described as exophytic and 3 as extramedullary with some degree of medullary invasion. Histological
examination revealed 9 WHO Grade II tumors, 4 Grade III tumors, and 1 myxopapillary tumor. Data obtained for
the remaining cases proved inconclusive. The clinical condition improved in 11 patients, remained stable in 2, and
worsened (recurrence or progression) in 6. Of the 4 patients with Grade II tumors who presented with recurrence or
neuraxis spreading, 3 had meningeal infiltration or adhesion to the pia mater, which does not rule out the possibility
of neoplastic remnants in that area.
Intradural extramedullary ependymomas are rare, they predominate in women in the 5th decade of life, and pain
is the most frequent initial symptom. The extent of resection and the presence of meningeal infiltration seem to be key
determinants of prognosis. The present case is the first intradural extramedullary ependymoma (with the exception of
those occurring at the conus medullaris and terminal filum) with multiple lesions at presentation.
(DOI: 10.3171/2010.9.SPINE09963)

Key Words      •      ependymoma      •      extramedullary ependymoma      •     

intradural ependymoma       •      multifocal ependymoma

pinal cord tumors can be classified as extradural lary tumors and occur predominantly in adults. The re­
(55%) or intradural (45%), the latter being either in­ ported cranial/spinal tumor ratio for ependymomas is
tramedullary (5%) or extramedullary (40%).22 Neu­­­­­ro­ 4:1, ranging from 3:1 to 20:1, depending on histological
fibromas, neuromas, and meningiomas account for roughly subtype.18,19,22 Intradural extramedullary ependymomas
60% of intradural extramedullary tumors and affect mainly are extremely rare except for those located at the termi­
adults, whereas intramedullary tumors are more common nal filum or conus medullaris.20,22 An extensive literature
in children. Ependymomas and astrocytomas are the main survey yielded 18 such cases.3,5–7,9–14,17,21,23,24,27,29,31 The
histological diagnoses in the children.22 present study reports the 19th case and reviews all cases
Ependymomas are the most common intramedul­ described to date.

J Neurosurg: Spine / December 10, 2010 1

E. A. Iunes et al.

Fig. 1.  Sagittal T2-weighted (A and C) and fat-suppressed, postcontrast T1-weighted (B and D) MR images of the cervicotho-
racic region demonstrating multiple intradural extramedullary lesions in the bulbomedullary junction, C2–3, and T6–11 with high
signal intensity on the T2-weighted images, cystic areas, and moderate and heterogeneous enhancement. Note the irregular and
thickened enhancement outlining the posterior surface of spinal cord.

Case Report

History and Examination. This 32-year-old man pre­

sented with progressive paresthesia in the lower limbs,
gait disturbance, and urinary retention during the preced­
ing month. Neurological examination showed hypesthe­
sia at the T-9 level, lower-limb hyperreflexia, Romberg
sign, and calcaneal gait. Muscle strength was preserved.
Initial spinal MR imaging revealed multiple intradural
extramedullary lesions in the bulbomedullary junction
and C2–3, T5–11, L-2, L-4, L-5, and sacrum that were
predominantly isointense on T1-weighted images and
hyperintense on T2-weighted and FLAIR images, with
moderate contrast enhancement (Figs. 1 and 2). Cranial
MR imaging showed an interpeduncular nodular lesion
with mild contrast enhancement (Fig. 3).
Operation. A T7–9 laminectomy was performed at the
site of the major compression of the spinal cord according
to the MR imaging findings. A brownish intradural extra­
medullary tumor compressing the spinal cord posteriorly
was immediately apparent after opening the dura. Under
microscopic assistance, no attachment of the tumor to the
dura or spinal cord was observed, but arachnoid infiltra­
tion was noted. The tumor was soft. After internal debulk­
ing of the lesion, a sharp dissection at the tumor–spinal
cord interface was performed, and the tumor was resected.
Because of the multifocal characteristic of the lesion and Fig. 2.  Sagittal fat-suppressed postcontrast T2-weighted (left) and
T1-weighted (right) MR images of the lumbar spine demonstrating in-
arachnoidal infiltration, the aim of the surgery was spinal tradural and extramedullary entities appearing as cervicothoracic le-
cord decompression instead of total resection. The histo­ sions at the level of L-4 and L-5. Superficial enhancement is observed
logical examination revealed a WHO Grade II ependy­ in the conus medullaris.

2 J Neurosurg: Spine / December 10, 2010

Multifocal intradural extramedullary ependymoma

Fig. 3.  Postcontrast FLAIR (left) and T1-weighted (right) MR imag-

es of the brain showing an interpeduncular nodular lesion hyperintense
on the FLAIR image and with mild contrast enhancement.

moma with hypercellular nodules showing a Ki 67 index

of 10% (Fig. 4).
Postoperative Course. Postoperatively, the patient de­
veloped a transient motor deficit (strength 4/5 in the ilio­
psoas, quadriceps, tibialis anterior, extensor hallucis lon­ Fig. 4.  Photomicrographs showing a moderately cellular ependymo-
gus, and gastrocnemius muscles). He was able to stand on ma with a monomorphic nuclear morphology and a perivascular pseu-
his own and walk with assistance. The patient received ad­ dorosette (A), perivascular pseudorosette (B), increased cellularity and
juvant chemotherapy consisting of 4 cycles of carboplatin pleomorphic area with 1 mitosis (C), and ependymal rosette (D). H & E,
(175 mg/m2/week for 4 weeks), followed by a 2-week break, original magnification × 100 (A and B); × 400 (C and D).
without objective response.
Ten months after surgery, the patient presented with Patients’ ages ranged from 24 to 69 years, a range similar
progressive paraparesis. He underwent a partial resection to that described for intramedullary cases, with predomi­
of the intradural extramedullary lesion between T-9 and nance in the 5th decade of life.20,22
T-10, which adhered to nerve roots without medullary in­ The initial symptoms were pain in 13 patients and
vasion. Histological examination again revealed a WHO medullary syndrome (with motor and/or sensory and/or
Grade II ependymoma. Regarding the intracranial lesion, sphincter control deficit) in 12 (data were not available for
it was never biopsied, but it was assumed to have the same 1 patient). Dorsalgia and radicular pain are the most fre­
histology because of the similarity of the MR imaging quently reported clinical symptoms, regardless of com­
characteristics. The tumor remained stable during follow- partment (intra- or extradural) or histological subtype.22
up. The patient underwent radiotherapy at 39.5 Gy (whole Intradural extramedullary ependymomas tend to follow
brain) and 36 Gy (neuraxis), but no objective response the same pattern, with pain being reported as the earliest
ensued. He refused further chemotherapy and 8 months symptom in the majority of cases described (13 [72.2%]
later developed a complete spinal cord syndrome and of 18 cases).
septic shock due to a urinary tract infection. The overall The time elapsed from symptom onset to diagnosis
survival was 105 weeks. ranged from 1 month to 8 years. The time interval from
the first clinical manifestation to diagnosis was less than
Discussion 1 year in most cases (12 [66.7%] of 18 cases). Diagno­
sis was delayed in some patients because of the lack of
We found 17 publications reporting 18 patients with available MR imaging at the time. Among the patients
intradural extramedullary ependymoma (2 of them were reported on after the advent of MR imaging, only 2 were
reported in a single publication by Hentschel et al.13). Ta­ diagnosed later than 1 year. Graça et al.12 reported on a
ble 1 shows the demographic, clinical, and follow-up data 67-year-old woman who presented with foot numbness
of all patients, including the patient in the present report. that was initially diagnosed as peripheral neuropathy.
Of the 19 patients, 15 were women and 4 were men. The definitive tumor diagnosis was reached 2 years after
A higher incidence among women has been observed in the initial symptom. Katoh et al.14 reported on a 24-year-
earlier studies.9,12 In a review paper of intradural extra­ old woman presenting with sporadic dorsalgia. Magnetic
medullary ependymomas, Duffau et al.9 postulated that resonance imaging was performed 3 years later, on mani­
a hormonal factor was involved. The higher prevalence festation of clinical features of medullary compression.
among females does not match epidemiological data on Magnetic resonance imaging is the gold standard
spinal tumors, which affect males and females at simi­ for diagnosing spinal tumors. Ependymomas usually en­
lar rates, except for meningiomas, which are more com­ hance uniformly after Gd administration.16,28 Tumor loca­
monly found among females, and intramedullary epen­ tion was distributed as follows: cervical in 2 patients, cer­
dymomas, which are more prevalent among males.18,19,22 vicothoracic in 3, thoracic in 11, lumbar in 2, and multiple

J Neurosurg: Spine / December 10, 2010 3

E. A. Iunes et al.
TABLE 1: Summary of the cases reported*

Clinical Duration of
Authors & Year Age, Sex (yrs) Features Symptoms (wks) Site Intraop WHO Grade Clinical Course Follow-Up (wks)
Cooper et al., 1951 40, F pain, MS 156 T EM/TR I† disease free 106
Cheng et al., 1996 47, F MS 34 T exo/TR myxo disease free NR
González et al., 1971 43, F MS 416 T EM/TR II disease free NR
Katoh et al., 1995 24, F pain 156 CT EMA/TR III disease free 26
Li & Holtås, 1992 NR, F NR NR L EM NR disease free NR
Oliver et al., 1981 34, F pain, MS 260 T EM III disease free 13
Wagle et al., 1988 41, F pain 52 T EMA/TR II† disease free NR
Wolfla et al., 1997 69, F pain 26 T EM/TR II† disease free 27
Duffau et al., 2000 43, F pain, MS 52 T EM/TR II disease free 106
Robles et al., 2005 47, F MS subacute T EM/TR II recurrence 98
Payer et al., 1999 62, F pain 39 T EM/TR II disease free NR
Shuurmans et al., 2006 29, F pain, MS 17 C EMA/TR III recurrence & death 106
Fuentes Rodríguez et al., 2004 47, F pain 78 L EM/TR II disease free NR
Cerase et al., 2006 56, M pain, MS 8 T EM/TR III recurrence & death 57
Graça et al., 2006 67, F MS 104 T EM/TR II recurrence 56
Hentschel et al., 2004 37, M pain, MS 17 CT exo/TR II stable disease 6
51, F pain 52 CT exo/TR II stable disease 2
Benzagmout et al., 2008 31, M pain, MS 52 C EM/TR II† recurrence NR after relapse
present case 32, M MS 4 ML EM/PR II progression & death 105

*  C = cervical; CT = cervicothoracic; EM = extramedullary; EMA = extramedullary with adhesion; exo = exophytic; L = lumbar; ML = multiple locations;
MS = medullary syndrome; myxo = myxopapillary; NR = not reported; PR = partial resection; T = thoracic; TR = total resection.
†  These grades are probable grades.

in 1 patient (present case).3,5–7,9–14,17,21,23,24,27,29,31 In contrast sion might go undetected, particularly if partial resection
to intramedullary ependymomas that clearly tend to de­ is considered.
velop at the cervical medulla,19,20 the predominance of the Clinical improvement and local control occurred in 11
thoracic location was noteworthy in the present review. patients,6,7,9–11,14,17,21,23,29,31 5 of whom were followed up for
Three of 5 tumors with cervical involvement extended 13–106 weeks.7,9,14,21,31 Data on follow-up were not available
into the thoracic region (cervicothoracic tumors). This for 6 patients.6,10,11,17,23,29 Two patients remained stable, al­
observation may suggest that they might actually be cer­ though the follow-up extended for only 2 and 6 weeks.13
vical intramedullary tumors (more prevalent) with extra­ Including the patient in the present case, recurrence or
medullary extension. The present case is the first of an progression occurred in 6 patients as follows:3,5,12,24,27 1
intradural extramedullary ependymoma (except for those patient developed distant spinal metastasis,24 2 had local
occurring in the conus medullaris and terminal filum) recurrence and distant spinal metastasis,5,12 1 had local re­
with multiple lesions at presentation. This presentation currence and cerebellar metastasis,3 and 1 had spinal and
had been previously described in myxopapillary ependy­ intracranial metastases.27 The patient in the present case
momas.30 presented with multiple lesions at diagnosis. Three pa­
Intraoperative reports described exophytic tumors tients, including the one in the present case, died of disease
in 3 cases (treated with total resection), extramedullary progression.5,27
tumors with some degree of medullary involvement in Histologically, 9 ependymomas were classified as
3 cases (treated with total resection), and 13 tumors de­ WHO Grade II, 1 was described as myxopapillary de­
scribed as exclusively extramedullary (of which 10 were spite the thoracic location, 4 were anaplastic (Grade III),
treated with total resection and 1 with partial resection; 3 were “probable” Grade II tumors, and 1 was a probable
in 2 cases the extent of resection was not specified). In the Grade I ependymoma. The descriptions available were
present case, the tumor was exclusively extramedullary, not detailed for the last 4 cases.
but it infiltrated the arachnoid membrane. Graça et al.12 Higher-grade gliomas are more prevalent in the ce­
reported a similar case of a Grade II tumor treated using rebral parenchyma, whereas lower-grade gliomas pre­
gross-total resection. The tumor presented with a “pachy­ vail in the medulla.22 The present review showed a clear
meningitis” that might have been attributable to neoplas­ predominance of low-grade ependymomas. Histological
tic infiltration and contributed to the poor outcome as grade does not seem to be the major determinant of clini­
observed in our patient. Finally, the true value of the sur­ cal outcome. Of the 6 cases with poor outcome,3,5,12,24,27
geon’s intraoperative observation should be emphasized, that is, those with recurrence or neuraxis spreading, only
since minimal medullary connections or arachnoid inva­ 2 had histological features of anaplastic ependymoma.5,27

4 J Neurosurg: Spine / December 10, 2010

Multifocal intradural extramedullary ependymoma

The 3 patients with WHO Grade II tumors with unfavor­ The thoracic location is the most common site for ex­
able outcome warrant further evaluation. The patient re­ tramedullary ependymomas, unlike intramedullary ep­
ported by Robles et al.24 underwent gross-total resection endymomas, which are mostly cervical. Multifocal pre­
of an anterolateral tumor, yet the authors reported adhe­ sentation at diagnosis had not been previously described.
sion to the pia mater, which does not rule out the possibil­ The prognosis seems to be related to the extent of resec­
ity of neoplastic remnants in that area. The local recur­ tion and the presence of meningeal infiltration.
rence was located in the posterior region, and histological
examination showed a Grade III ependymoma. Taking Disclosure
into account that the lesion was only partially resected, a
sampling error might be inferred (the pial portion might The authors report no conflict of interest concerning the mate­
rials or methods used in this study or the findings specified in this
be a Grade III ependymoma). The patient reported on by paper.
Graça et al.12 presented with recurrence and spinal me­ Author contributions to the study and manuscript prepara­
tastasis, but the tumor remained classified as a Grade II tion include the following. Conception and design: Malheiros.
tumor. An “important arachnoid inflammatory reaction” Acquisition of data: Iunes, Stávale, Pessoa. Analysis and interpreta­
was also described, which might characterize a neoplastic tion of data: Iunes, Stávale, Pessoa, Neto. Drafting the article: Iunes,
infiltration and actually a partial resection, accounting for Neto, Malheiros. Critically revising the article: Neto, Malheiros.
the unfavorable outcome. The patient in the present case Reviewed final version of the manuscript and approved it for
sub­mission: all authors. Administrative/technical/material support:
also had a WHO Grade II ependymoma. The pachymen­ Ansai, Onishi. Study supervision: Bonatelli, Cavalheiro, Neto, Mal­
ingitis observed during surgery might in fact have been heiros.
tumoral infiltration that led to sampling errors. However,
the clinical feature of dissemination at presentation was References
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Jorquera M, et al: Intradural extramedullary spinal ependy­ Please include this information when citing this paper: published
moma: a benign pathology? Spine 30:E251–E254, 2005 online December 10, 2010; DOI: 10.3171/2010.9.SPINE09963.
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6 J Neurosurg: Spine / December 10, 2010