Multifocal intradural extramedullary ependymoma
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Transcript of Multifocal intradural extramedullary ependymoma
J Neurosurg: Spine / December 10, 2010
DOI: 10.3171/2010.9.SPINE09963
1
Spinal cord tumors can be classified as extradural (55%) or intradural (45%), the latter being either intramedullary (5%) or extramedullary (40%).22 Neu ro
fibromas, neuromas, and meningiomas account for roughly 60% of intradural extramedullary tumors and affect mainly adults, whereas intramedullary tumors are more common in children. Ependymomas and astrocytomas are the main histological diagnoses in the children.22
Ependymomas are the most common intramedul
lary tumors and occur predominantly in adults. The reported cranial/spinal tumor ratio for ependymomas is 4:1, ranging from 3:1 to 20:1, depending on histological subtype.18,19,22 Intradural extramedullary ependymomas are extremely rare except for those located at the terminal filum or conus medullaris.20,22 An extensive literature survey yielded 18 such cases.3,5–7,9–14,17,21,23,24,27,29,31 The present study reports the 19th case and reviews all cases described to date.
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 bulbomedullary junction and C2–3, T5–11, L-2, L-4, L-5, and sacrum. Histological examination revealed a WHO Grade II ependymoma.
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 patients; 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
E. A. Iunes et al.
2 J Neurosurg: Spine / December 10, 2010
Case Report
History and Examination. This 32yearold man presented with progressive paresthesia in the lower limbs, gait disturbance, and urinary retention during the preceding month. Neurological examination showed hypesthesia 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, L2, L4, L5, and sacrum that were predominantly isointense on T1weighted 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 extramedullary 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 infiltration was noted. The tumor was soft. After internal debulking 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 arachnoidal infiltration, the aim of the surgery was spinal cord decompression instead of total resection. The histological examination revealed a WHO Grade II ependy
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.
Fig. 2. Sagittal fat-suppressed postcontrast T2-weighted (left) and T1-weighted (right) MR images of the lumbar spine demonstrating in-tradural and extramedullary entities appearing as cervicothoracic le-sions at the level of L-4 and L-5. Superficial enhancement is observed in the conus medullaris.
J Neurosurg: Spine / December 10, 2010
Multifocal intradural extramedullary ependymoma
3
moma with hypercellular nodules showing a Ki 67 index of 10% (Fig. 4).
Postoperative Course. Postoperatively, the patient developed a transient motor deficit (strength 4/5 in the iliopsoas, quadriceps, tibialis anterior, extensor hallucis longus, and gastrocnemius muscles). He was able to stand on his own and walk with assistance. The patient received adjuvant chemotherapy consisting of 4 cycles of carboplatin (175 mg/m2/week for 4 weeks), followed by a 2-week break, without objective response.
Ten months after surgery, the patient presented with progressive paraparesis. He underwent a partial resection of the intradural extramedullary lesion between T-9 and T-10, which adhered to nerve roots without medullary invasion. Histological examination again revealed a WHO Grade II ependymoma. Regarding the intracranial lesion, it was never biopsied, but it was assumed to have the same histology because of the similarity of the MR imaging characteristics. The tumor remained stable during follow-up. The patient underwent radiotherapy at 39.5 Gy (whole brain) and 36 Gy (neuraxis), but no objective response ensued. He refused further chemotherapy and 8 months later developed a complete spinal cord syndrome and septic shock due to a urinary tract infection. The overall survival was 105 weeks.
DiscussionWe found 17 publications reporting 18 patients with
intradural extramedullary ependymoma (2 of them were reported in a single publication by Hentschel et al.13). Table 1 shows the demographic, clinical, and follow-up data of all patients, including the patient in the present report.
Of the 19 patients, 15 were women and 4 were men. A higher incidence among women has been observed in earlier studies.9,12 In a review paper of intradural extramedullary ependymomas, Duffau et al.9 postulated that a hormonal factor was involved. The higher prevalence among females does not match epidemiological data on spinal tumors, which affect males and females at similar rates, except for meningiomas, which are more commonly found among females, and intramedullary ependymomas, which are more prevalent among males.18,19,22
Patients’ ages ranged from 24 to 69 years, a range similar to that described for intramedullary cases, with predominance in the 5th decade of life.20,22
The initial symptoms were pain in 13 patients and medullary syndrome (with motor and/or sensory and/or sphincter control deficit) in 12 (data were not available for 1 patient). Dorsalgia and radicular pain are the most frequently reported clinical symptoms, regardless of compartment (intra- or extradural) or histological subtype.22 Intradural extramedullary ependymomas tend to follow the same pattern, with pain being reported as the earliest symptom in the majority of cases described (13 [72.2%] of 18 cases).
The time elapsed from symptom onset to diagnosis ranged from 1 month to 8 years. The time interval from the first clinical manifestation to diagnosis was less than 1 year in most cases (12 [66.7%] of 18 cases). Diagnosis was delayed in some patients because of the lack of available MR imaging at the time. Among the patients reported on after the advent of MR imaging, only 2 were diagnosed later than 1 year. Graça et al.12 reported on a 67-year-old woman who presented with foot numbness that was initially diagnosed as peripheral neuropathy. The definitive tumor diagnosis was reached 2 years after the initial symptom. Katoh et al.14 reported on a 24yearold woman presenting with sporadic dorsalgia. Magnetic resonance imaging was performed 3 years later, on manifestation of clinical features of medullary compression.
Magnetic resonance imaging is the gold standard for diagnosing spinal tumors. Ependymomas usually enhance uniformly after Gd administration.16,28 Tumor location was distributed as follows: cervical in 2 patients, cervicothoracic in 3, thoracic in 11, lumbar in 2, and multiple
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.
Fig. 4. Photomicrographs showing a moderately cellular ependymo-ma with a monomorphic nuclear morphology and a perivascular pseu-dorosette (A), perivascular pseudorosette (B), increased cellularity and pleomorphic area with 1 mitosis (C), and ependymal rosette (D). H & E, original magnification × 100 (A and B); × 400 (C and D).
E. A. Iunes et al.
4 J Neurosurg: Spine / December 10, 2010
in 1 patient (present case).3,5–7,9–14,17,21,23,24,27,29,31 In contrast to intramedullary ependymomas that clearly tend to develop at the cervical medulla,19,20 the predominance of the thoracic location was noteworthy in the present review. Three of 5 tumors with cervical involvement extended into the thoracic region (cervicothoracic tumors). This observation may suggest that they might actually be cervical intramedullary tumors (more prevalent) with extramedullary extension. The present case is the first of an intradural extramedullary ependymoma (except for those occurring in the conus medullaris and terminal filum) with multiple lesions at presentation. This presentation had been previously described in myxopapillary ependymomas.30
Intraoperative reports described exophytic tumors in 3 cases (treated with total resection), extramedullary tumors with some degree of medullary involvement in 3 cases (treated with total resection), and 13 tumors described as exclusively extramedullary (of which 10 were treated with total resection and 1 with partial resection; in 2 cases the extent of resection was not specified). In the present case, the tumor was exclusively extramedullary, but it infiltrated the arachnoid membrane. Graça et al.12 reported a similar case of a Grade II tumor treated using grosstotal resection. The tumor presented with a “pachymeningitis” that might have been attributable to neoplastic infiltration and contributed to the poor outcome as observed in our patient. Finally, the true value of the surgeon’s intraoperative observation should be emphasized, since minimal medullary connections or arachnoid inva
sion might go undetected, particularly if partial resection is considered.
Clinical improvement and local control occurred in 11 patients,6,7,9–11,14,17,21,23,29,31 5 of whom were followed up for 13–106 weeks.7,9,14,21,31 Data on follow-up were not available for 6 patients.6,10,11,17,23,29 Two patients remained stable, although the follow-up extended for only 2 and 6 weeks.13 Including the patient in the present case, recurrence or progression occurred in 6 patients as follows:3,5,12,24,27 1 patient developed distant spinal metastasis,24 2 had local recurrence and distant spinal metastasis,5,12 1 had local recurrence and cerebellar metastasis,3 and 1 had spinal and intracranial metastases.27 The patient in the present case presented with multiple lesions at diagnosis. Three patients, including the one in the present case, died of disease progression.5,27
Histologically, 9 ependymomas were classified as WHO Grade II, 1 was described as myxopapillary despite the thoracic location, 4 were anaplastic (Grade III), 3 were “probable” Grade II tumors, and 1 was a probable Grade I ependymoma. The descriptions available were not detailed for the last 4 cases.
Higher-grade gliomas are more prevalent in the cerebral parenchyma, whereas lowergrade gliomas prevail in the medulla.22 The present review showed a clear predominance of low-grade ependymomas. Histological grade does not seem to be the major determinant of clinical outcome. Of the 6 cases with poor outcome,3,5,12,24,27 that is, those with recurrence or neuraxis spreading, only 2 had histological features of anaplastic ependymoma.5,27
TABLE 1: Summary of the cases reported*
Authors & Year Age, Sex (yrs)Clinical
FeaturesDuration of
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 106Cheng et al., 1996 47, F MS 34 T exo/TR myxo disease free NRGonzález et al., 1971 43, F MS 416 T EM/TR II disease free NRKatoh 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 NROliver 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 NRWolfla 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 NRShuurmans 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 NRCerase 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 relapsepresent 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.
J Neurosurg: Spine / December 10, 2010
Multifocal intradural extramedullary ependymoma
5
The 3 patients with WHO Grade II tumors with unfavorable outcome warrant further evaluation. The patient reported by Robles et al.24 underwent grosstotal resection of an anterolateral tumor, yet the authors reported adhesion to the pia mater, which does not rule out the possibility of neoplastic remnants in that area. The local recurrence was located in the posterior region, and histological examination showed a Grade III ependymoma. Taking into account that the lesion was only partially resected, a sampling error might be inferred (the pial portion might be a Grade III ependymoma). The patient reported on by Graça et al.12 presented with recurrence and spinal metastasis, but the tumor remained classified as a Grade II tumor. An “important arachnoid inflammatory reaction” was also described, which might characterize a neoplastic infiltration and actually a partial resection, accounting for the unfavorable outcome. The patient in the present case also had a WHO Grade II ependymoma. The pachymeningitis observed during surgery might in fact have been tumoral infiltration that led to sampling errors. However, the clinical feature of dissemination at presentation was irrefutable and may also have been associated with the unfavorable outcome. The patient described by Benzag-mout et al.3 also had a poor outcome with cerebellar metastasis and local recurrence. The tumor was initially classified as a “benign ependymoma,” and the authors did not report on the follow-up after recurrence.
Two patients with WHO Grade III ependymomas with a favorable outcome were described by Katoh et al.14 and Oliver et al.21 However, the follow-up reported was short (only 26 and 13 weeks, respectively).
The origin of intradural extramedullary ependymoma has been attributed to the presence of heterotopic glial cells, since the earliest report by Cooper et al.7 This observation implies the occurrence of invagination of the neuraxis into the extramedullary space, evidenced by an encapsulated appearance (encapsulation by pia mater and arachnoid membrane) and absence of medullary connection. These cells evolve to a tumor within the intradural extramedullary space. The same hypothesis has been proposed to explain the origin of gliomas occurring outside the neuraxis, including nasal and sacral gliomas.1,2,4,8,15,25,26 The presence of a medullary connection does not rule out the hypothesis of an intramedullary tumor extending to the extramedullary compartment. Identification of exclusively extramedullary cases can be biased by subjective interpretation and by the resolution of surgical microscopes, making it difficult to rule out medullary connection. From a practical standpoint, however, all the cases reported appeared as intradural and extramedullary lesions on the images, and the importance of these reports may lie in considering ependymomas, although rare, as a differential diagnosis of tumors at this location.
ConclusionsIntradural extramedullary ependymomas are ex
tremely rare and predominate in women in the 5th decade of life. Pain is the most frequent initial symptom, akin to other tumors of the medullary canal. Magnetic resonance imaging of the entire neuraxis is essential to rule out intracranial ependymomas with metastasis to the neuraxis.
The thoracic location is the most common site for extramedullary ependymomas, unlike intramedullary ependymomas, which are mostly cervical. Multifocal presentation at diagnosis had not been previously described. The prognosis seems to be related to the extent of resection and the presence of meningeal infiltration.
Disclosure
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Author contributions to the study and manuscript preparation include the following. Conception and design: Malheiros. Acquisition of data: Iunes, Stávale, Pessoa. Analysis and interpretation of data: Iunes, Stávale, Pessoa, Neto. Drafting the article: Iunes, Neto, Malheiros. Critically revising the article: Neto, Malheiros. Reviewed final version of the manuscript and approved it for sub mission: all authors. Administrative/technical/material support: Ansai, Onishi. Study supervision: Bonatelli, Cavalheiro, Neto, Mal-heiros.
References
1. Anglade MP: Le gliome des fosses nasales. Étude clinique et anatomo-pathologique. Presse Med 28:464, 1920
2. Bailey OT: Relation of glioma of the leptomeninges to neuroglia nests: report of a case of astrocytoma of the leptomeninges. Arch Path 21:584–600, 1936
3. Benzagmout M, Boujraf S, Oulali N, Chbani L, Amarti A, Chakour K, et al: Intradural extramedullary ependymoma: is there constantly a hormonal relationship? Surg Neurol 70: 536–538, 2008
4. Browder J: Encephaloma or the socalled nasal glioma. Ann Otol Rhinol Laryngol 38:395–403, 1929
5. Cerase A, Venturi C, Oliveri G, De Falco D, Miracco C: Intradural extramedullary spinal anaplastic ependymoma. Case illustration. J Neurosurg Spine 5:476, 2006
6. Cheng CH, Lee TC, Huang HY, Lui CC: Extramedullary thoracic myxopapillary ependymoma—a case report of a rare tumour. Ann Acad Med Singapore 25:869–872, 1996
7. Cooper IS, Craig WM, Kernohan JW: Tumors of the spinal cord; primary extramedullary gliomas. Surg Gynecol Obstet 92:183–190, 1951
8. Crook M: Congenital ganglio-neuroma of nose, report of a case. J S Carolina Med Assoc 36:159–160, 1940
9. Duffau H, Gazzaz M, Kujas M, Fohanno D: Primary intradural extramedullary ependymoma: case report and review of the literature. Spine 25:1993–1995, 2000
10. Fuentes Rodríguez N, de la Paz Rivero M, Prince López JA, Salas Rubio JH: Ependimoma intradural extramedular primario. Rev Cuba Med Mil 33, 2004 (http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0138-65572004000100009&lng=en&nrm=iso) [Accessed October 27, 2010]
11. González Feria L, Fernández Martín F, Ginovés Sierra M, Galera Davidson H: [Giant dorsal extramedullary ependymoma.] Arch Neurobiol (Madr) 34:325–332, 1971 (Spn)
12. Graça J, Gültasli N, D’Haene N, Brotchi J, Salmon I, Balériaux D: Cystic extramedullary ependymoma. AJNR Am J Neu rora diol 27:818–821, 2006
13. Hentschel SJ, McCutcheon IE, Ginsberg L, Weinberg JS: Ex-o phytic ependymomas of the spinal cord. Acta Neurochir (Wien) 146:1047–1050, 2004
14. Katoh S, Ikata T, Inoue A, Takahashi M: Intradural extramedullary ependymoma. A case report. Spine 20:2036–2038, 1995
15. Kernohan JW, Fletcher-Kernohan EM: Ependymomas: a study of 109 cases. Assoc Res Nerv Ment Dis 16:182–209, 1937
16. Li MH, Holtås S: MR imaging of spinal intramedullary tumors. Acta Radiol 32:505–513, 1991
E. A. Iunes et al.
6 J Neurosurg: Spine / December 10, 2010
17. Li MH, Holtås S, Larsson EM: MR imaging of intradural extramedullary tumors. Acta Radiol 33:207–212, 1992
18. McCormick PC, Post KD, Stein BM: Intradural extramedullary tumors in adults. Neurosurg Clin N Am 1:591–608, 1990
19. McCormick PC, Stein BM: Intramedullary tumors in adults. Neurosurg Clin N Am 1:609–630, 1990
20. McCormick PC, Torres R, Post KD, Stein BM: Intramedullary ependymoma of the spinal cord. J Neurosurg 72:523–532, 1990
21. Oliver B, de Castro A, Sarmiento MA, Argüello C, Blaźquez MG: [Dorsal extramedullary ependymoma (author’s transl).] Arch Neurobiol (Madr) 44:215–224, 1981 (Spn)
22. Parsa AT, Lee J, Parney IF, Weinstein P, McCormick PC, Ames C: Spinal cord and intradural-extraparenchymal spinal tumors: current best care practices and strategies. J Neurooncol 69:291–318, 2004
23. Payer M, Yonekawa Y, Imhof HG: Solitary thoracic intradural extramedullary ependymoma. J Clin Neurosci 6:344–345, 1999
24. Robles SG, Saldaña C, Boto GR, Martinez A, Zamarron AP, Jorquera M, et al: Intradural extramedullary spinal ependymoma: a benign pathology? Spine 30:E251–E254, 2005
25. Rocher HL, Anglade M: Les fibrogliomes de la région nasale. Rev Chir 62:147–178, 1924
26. Roussy G, Cornil L: Les tumeurs méningées. Ann d’Anat Path 2:63–79, 1925
27. Schuurmans M, Vanneste JAN, Verstegen MJT, van Furth WR: Spinal extramedullary anaplastic ependymoma with spinal and intracranial metastases. J Neurooncol 79:57–59, 2006
28. Sun B, Wang C, Wang J, Liu A: MRI features of intramedullary spinal cord ependymomas. J Neuroimaging 13:346–351, 2003
29. Wagle WA, Jaufman B, Mincy JE: Intradural extramedullary ependymoma: MR-pathologic correlation. J Comput Assist Tomogr 12:705–707, 1988
30. Woesler B, Moskopp D, Kuchelmeister K, Schul C, Wassmann H: Intracranial metastasis of a spinal myxopapillary ependymoma. A case report. Neurosurg Rev 21:62–65, 1998
31. Wolfla CE, Azzarelli B, Shah MV: Primary extramedullary ependymoma of the thoracic spine. Case illustration. J Neurosurg 87:643, 1997
Manuscript submitted December 8, 2009.Accepted September 22, 2010.Please include this information when citing this paper: published
online December 10, 2010; DOI: 10.3171/2010.9.SPINE09963.Address correspondence to: Eduardo Augusto Iunes, M.D.,
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Rua Napoleão de Barros, 715/6th floor, São Paulo, SP, Brazil, 04024002. email: [email protected].