Intracranial metastasis from a spinal cord primitive neuroectodermal tumor: Case report

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Intracranial Metastasis from a Spinal Cord Primitive Neuroectodermal Tumor : Case Report Hidenori Ogasawara, M .D., Katsuzo Kiya, M .D., Kaoru Kurisu, M.D., Zainal Muttaqin, M.D., Tohru Uozumi, M.D., Kazuhiko Sugiyama, M .D., Yukihiko Kawamoto, M .D ., and Koji lida, M .D. Departments of Neurosurgery, Hiroshima University School of Medicine, Hiroshima, National Hiroshima Hospital, Hiroshima, Futami Central Hospital, Miyoshi, National Kure Hospital, Kure, Japan

Ogasawara H, Kiya K, Kurisu K, Muttagin Z, Uozumi T, Sugiyama K, Kawamoto Y, lida K. Intracranial metastasis from a spinal cord primitive neuroectodermal tumor : case report. Surg Neurol 1992 ;3` :30 -1-1 . A patient with intracranial seeding from a spinal cord primitive neuroectodermal tumor with ependymal differentiation is presented . The first and second stages of intracranial dissemination were well controlled by a combination of irradiation and chemotherapy . The authors review previously published cases and discuss the possible mechanism of seeding from the spinal cord to the intracranial region. KEY WORDS : Primitive neuroectodermal tumor ; Metastasis ; Spinal cord tumor

Primitive neuroectodermal tumor (PNET), a term proposed by Hart and Earle {91, is an uncommon tumor of the central nervous system, showing characteristic occurrence in the cerebrum of children and young adults . Cases of PNET have been increasingly reported in recent years, but there are still very few reports of PNET originating in the spinal cord . In addition, seeding from spinal cord tumors to the intracranial region is much less common . We report a patient with primary spinal cord PNET who showed the signs and symptoms of intracranial metastatic tumor . The pathophysiology of tumor metastasis and therapeutic results are discussed .

Case Report A 16-year-old girl was admitted to the orthopedic department of a community hospital in May 1988 for evaluHidenori Ogasawara, M .D ., 082-251Department of Neurosurgery, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan . Received July 23, 1991 ; accepted October 16, 1991 . Address reprint requests to :

1111,

© 1992 by Elsevier Science Publishing Co ., Inc .

ation of a 2-month history of lower back pain and a 1-month history of sphincter disturbance . A neurological examination revealed mild spastic paraparesis . An intramedullary tumor at the L2 level was subtotally removed on May 25, 1988 . Microscopic examination of the resected specimen showed diffuse proliferation of small undifferentiated cells, which had scanty cytoplasm and a spindle- or polygonal-shaped nucleus rich in chromatin . Mitotic figures and rosette formation were observed in part of the tissue (Figure 1 A) . Immunohistochemical staining for glial fihrillary acidic protein, vimentin, S-100 protein, and neuron-specific enolase demonstrated focal positivity (Figure 1 B, C) . Electron microscopy revealed that the majority of the tumor cells were undifferentiated small cells with little cytoplasm and few organelles . functional complexes between microvilli and cells were also slightly evident (Figure 2) . The pathological diagnosis was PNET with ependymal differentiation . Postoperatively the patient had relief from hack pain and sphincter disturbance . In July 1988 the patient was admitted to our hospital because of unconsciousness with vomiting . Computed tomography (CT) scan revealed moderate hydrocephalus with abnormal contrast-enhanced lesions around the ventricles, cistern around the brain stem, and the corpus callosum (Figure 3) . A ventricular drain was inserted, and radiation therapy (whole-brain, 45 .4 Gy ; wholespine, 36 Gy) and chemotherapy {1-(2-chloroethyl)-3methyl-D-glucopyranos-6-yl)-1-nitrosourea (MCNU) ; cisplatin] were administered . Symptomatic relief and complete tumor disappearance were achieved . In August 1989 the patient was admitted again owing to recurrence of a tumor around the anterior horn of the left lateral ventricle (Figure 4) . Local brain irradiation of 20 Gy and chemotherapy consisting of cisplatin and etoposide were given every 6 weeks . A CT scan after the third course of chemotherapy showed complete response to this treatment. In June 1990 the patient developed left hemiparesis 0090-3(119192/55 .00



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Figure l . Photomicrograph of the spinal tumor of the patient . (A) Diffuse proliferation of small undifferentiated ce/G . Perivascular pseudorosette formation as evidence of ependymal differentiation (hematoxylin and eosin x 100). Scattered undifferentiated cells stain positively for (B) GPAP and (C) vimentin (x 100) .

Figure2 . Electron micrograph of the spinal tumor showing the undifferentiated small yells with little cytoplasm and few organelles . The junction! complex and microvilli are slightly seen (bar = 7 µm) .



Metastasis from Spinal Cord PNET

Figure 3 . CT scan at thefarst intracranial metastasis showing hydrocephalus with abnormal contras enhancement of the ependyma, cistern around the brain stem, and the corpus callosum . (Top) Plain CT. (Bottom) Contract-enhanced CT.

and was admitted again. A CT scan showed multiple recurrent tumors in the cerebral hemispheres and lateral ventricular wall (Figure 5) . Symptomatic relief and partial response that was evident on CT scan were achieved following combined chemotherapy (two courses of carboplatin, etoposide, and vincristine every 4 weeks) . No spinal lesion was identifiable by magnetic resonance imaging (MRI) at this time . In August 1990 the patient suffered from convulsions and loss of consciousness because of enlargement of the tumor . Despite treatment with carhoplatin, vincristine, adriamycin, peplomycin, and cyclophosphamide, she became worse and died of pneumonia 29 months after the initial diagnosis . Permission for postmortem examination was not granted . Discussion The term PNET was first proposed by Hart and Earle [91 in 1973 . This tumor has common pathological char-

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acteristics : (1) It predominantly occurs in early life and (2) is clinically malignant ; (3) it occurs in the cerebrum (usually being hemispheric and deep) ; (4) it is grossly cystic and hemorrhagic with sharp borders and (5) is microscopically malignant and predominantly undifferentiated with evidence of focal attempts to differentiate along glial and neuronal lines ; and (6) it has a prominent mesenchymal component with at least 90%-95% undifferentiated cells [7] . The initial tumor site is primarily the frontal (34%) or parietal (29%) lobes . PNET originating from the ventricular system is uncommon (4 .5%) [2] . PNET originating in the spinal cord, as observed in this case, is also rare, and only 12 such cases have been reported [3,4,7,9,18,20,2 11 (Table 1) . The clinical characteristics in the 13 cases of spinal cord PNET including ours were as follows . (1) Five of the 13 cases were adults . (2) Males were predominantly affected . (3) The tumor was frequently located at lower spinal levels : cervical in three cases, thoracolumbar in two, and cauda equina in six . (4 The survival time after diagnosis was less than 2 years in two thirds of the cases, showing the same poor prognosis as primary brain PNET .



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Figure 4. Contrast-enhanced CT scan at the second Putastatti shooing the tumor around the anterior horn of the left lateral ventricle .

PNET readily disseminates, and dissemination to the subarachnoid space along the cerebrospinal fluid (CSF) pathway was reported in 12 (92%) of 13 autopsy cases [5,9,13,15] . However, PNET originating in the spinal cord rarely disseminates in an ascending manner into the

Table

intracranial space, and only two such cases have been reported [13,18] . The intracranial dissemination in these two cases was confirmed by autopsy . On the other hand, our case report seems to be the first in which the symptoms and signs of intracranial dissemination became evident during life and were successfully treated . In this case neither CT scan nor MRI was performed for investigation of intracranial lesions at the time of development of spinal cord signs . No histological specimens of the intracranial tumors appearing in the periventricular regions were obtained . Therefore it is difficult to be sure that the primary spinal cord PNET actually disseminated to the intracranial space . However, no neurological findings suggestive of intracranial tumors were noted until about 2 months after surgery for the spinal tumor . Moreover, a CT scan performed at the time of development of the intracranial neurological symptoms showed no major space-occupying lesions in the brain, and in fact it suggested dissemination in the cistern around the brain stem, basal cistern, and the ventricular walls . From these findings it seems reasonable to presume that the occurrence of the intracranial lesions was secondary to the dissemination of the primary spinal cord tumor . Dispersion of tumor cells through the subarachnoid space will follow the pathway of bulk CSF flow and cause obliteration of the basal cisterns, development of hydrocephalus, and ventricular reflux of tumor cells, thus promoting metastasis to the ventricular ependyma, which is readily damaged by hydrocephalus {1,6,10,17,19] . In addition, most of the reported cases with intracranial metastasis of spinal cord glioma underwent surgery for the spinal

1 . Reported Cases of Spinal PNET

Author

Age (yr)/ sex

Primary site of tumor

Interval, onset to death

Radiation therapy

Chemotherapy

Smith et al [21) Kosnik et al [13]

24/M 10>

Cauda equina Cervical

10 too 2 yr>

Yes Yes

No MTX, VCR

Cervical Thoracolumbar Lumbosacral Lower spinal cord Lower spinal cord Cauda equina Cauda equina Cauda equina Cervical Thoracolumbosacral

2 yr> 2 yr> 12 moK 3 mo 19 me 1 yr 6 me 3 yr< 3 yr 6 me 3 yr 1 yr 8 mu

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

PDN, CCNU

Baum et al [3) Priest et at [18] Bruno et al [4] Kepes et al {I1)

10> 10> 0/M 5/M 14/F 247M 56/M 39/M

Cauda equina

2 yr 5 inn

Yes

Sevick et at [20] Freyer et al [7]

261M

Ogasawara et at

16/F

7/M

No VCR, CPM No CPM, PDN, MTX, Ara-C No No No VCR, CDDP, PDN, HU PCZ, CCNU, CPM, VP-16 ifosfamide MCNU, CDDP, VP-16, CBDCA VCR, CPM, ADR, PEP

Extraspinal metastasis Lung Lung, bone, lymph node Intracranial

Intracranial

Pleura, bone, lymph node

Intracranial

ADR, adriamycin ; Ara-C, cyrosine arabinoside ; CBDCA, carboplarin ; CCNU, i-(2-rhloroethyl)-3-yclohexyl-I-nitrosnurea ; CDDP, cisplarin ; CPM, cyclophosphamide ; HU, hydroxvurea; MCNU, 1-(2-chloroethyl)-3-methyl-D-glucopyranos-6yl)-I-nitmxovrea ; MTX, merhouexare; PCZ, pmcarbaxine; PDN, predonisone, PEP, peplomycin ; PNET, primitive neuroecrodermal tumor; VCR, vincrisrine ; VP-16, emposide .



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Metastasis from Spinal Cord PNET

Figure 5 . Contrast-enhanced CT start at the third metastasis showing the multiple tumors in the bilateral cerebral bemispberes and lateral ventricle wall .

tumor, and dissemination of the tumor to the subarachnoid space is reported to be enhanced by surgical manipulation [1,6,17,22} . The optimal therapy for PNET is uncertain . Radical tumor removal, as much as possible if practicable, followed by irradiation of the whole cerebrospinal axis, is recommended [2,8,13] . Early onset of chemotherapy in conjunction with radiation therapy may improve the survival time [2] . However, the prognosis of this disease is very poor [9,13,16] . Ashwal et al [2] reported that the mean survival of 138 cases reviewed was 26 months, and the mean time to recurrence was 19 .9 months (range 3-36 months) . In our case, a complete response was obtained by chemotherapy with cisplatin and etoposide after intracranial recurrence . The combined use of cisplarin and etoposide is known to be effective for intracranial malignant germ cell tumors [ 12}, and it was also recently reported to be effective for medulloblastomas [14] . PNET is often histologically indistinguishable from medulloblastoma and has a similar tendency for CSF dissemination . There is no consensus regarding the optimal chemotherapeutic agents for this rare lesion . How-

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ever, adjuvant chemotherapy with agents such as cisplatin and etoposide may he useful .

References 1 . Andrews AA, Enriques L, Renaudin JU . Spinal intramedullary gliohlastoma with intracranial seeding . Report of a case . Arch Neurol 1978 ; 35 :244-5 . 2 . Ashwal S, Hinshaw DB, Bedros A . CNS primitive neuroectodermal rumors of childhood . Med Pediarr Once] 1984 ;12 :180-8 . . 3 Baum ES, Morgan ER, Dal Canto MC, West PM . Review of experience with primitive neuroecrodermal tumors of childhood . In : Humphrey GB, Dehner LP, eds . Pediatric oncology 1 . The Hague : Marrinus Niihoff, 1981 :239-42 . 4 . Bruno LA, Rorke LB, Norris DG . Primitive neuroectodermal rumors of infancy and childhood . In : Humphrey GB, Dehner LP, eds . Pediatric Oncology 1 . The Hague : Matinus Nijhnff, 1981 :265-' . 5 . Duffner PK, Cohen ME, Heffner RR, Freeman Al. Primitive neuroecrodermal rumors of childhood . An approach to therapy . J Neurosurg 1981 ;55 :376-81 . 6 . Eden KC . Dissemination of a glioma of the spinal cord in the leptumeninges . Brain 1938 ;61 :298-310 . 7 . Freyer DR, Hutchinson RJ, McKeever PE . Primary primitive neuroectodermal tumor of the spinal cord with neural tube defect . Pediarr Neurosci 1989 ;15 :181-7 . 8 . Gaffney CC, Sloane JP, Bradley NJ, Bloom HJG . Primitive neuroecrodermal rumors of the cerebrum . .) Neuro-Oncol 1985 ;3 :23-33 .



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9 . Hart MN, Earle KM . Primitive neuroectodermal tumors of the brain in children . Cancer 1973 ;32 :890-7 . 10 . Johnson DL, Schwarz S . Intracranial metastasis from malignant spinal-cord astrocytoma. J Neurosurg 1987 ;66 :621-5 . 11 . Kepes JJ, Belton K, Roessmann U . Primitive neuroectodermal rumors of the cauda equina in adults with no detectable primary intracranial neoplasm . Three case studies . Clin Neuroparhol 1985 ;4 :1-11 . 12 . Kohayashi T, Yoshida J, Ishiyama I, Noda 8, Kim A, Kida Y . Combination chemotherapy with cisplatin and etoposide for malignant intracranial germ cell tumors . J Neurosurg 1989 ; 70:676-81 . 13 . Kosnik EJ, Boesel CP, Bay), Sayers MP . Primitive neuroectoder mal tumors of the central nervous system it) children . J Neurosurg 1978 ;48 :741-6 . 14 . Kovnar EH, Kellie SJ, Horowitz ME, Sanford RA, Langston JW, Mulhern RK, Jenkins JJ, Douglass, Etcubanas EE, Fairclough DL, Kun LE . Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system . A phase 11 study . J Clin Oncol 1990 ;8 :330-6 . 15 . Markesbery MR . Challa VR . Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum . Cancer 1979 ;44 :141-7 .

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16 . Parker JC Jr, Mortara RH, McCloskey JJ. Biological behavior in primitive neuroectodermal tumors . Significant supratentorial gliomas. Surg Neurol 19 7 5A :383-817 . Perese DM, Slepian A, Nigogosyan G . Postoperative dissemination of astrocytoma of the spinal cord along with ventricles of the brain . A case report. J Neurosurg 1987 ;66621-5 . 18 . Priest J, Definer LP, Sung JH, Nesbit ME . Primitive neuroectodermal tumors . Embryonal gliomas of childhood . A clinicoparhologic study of 12 cases . In : Humphrey GB, Definer LP, eds . Pediatric ontology 1 . The Hague : Martinus Nijhuff, 1981 : 247-64 . 19 . Russel DS, Rubinstein LJ . Pathology of rumors of the nervous system . 5th ed . London : Edward Arnold, 1989 :430-7 . 20 . Sevick RJ, Johns RD, Curry BJ . Primary spinal primitive neuroectodermal rumor with exrraneural metastasis . Am J Nucl Radiol 1987 1 8.1151-2 . 21 . Smith DR, Hardman JM, Earle KE . Metastasizing neuroectodermal tumors of the central nervous system . J Neurosurg 1969 ; 31 :50-8 . 22 . Yamaguchi, T, Kikuchi H, Higashi K, Gore Y, Imataka K . Intracranial metastasis of a spinal cord astrocytoma . Case report . Neurol Med Chic (Tokyo) 1990 ;30 :69-73 .