Superficial cerebral astrocytoma attached to dura: Report of six cases in infants

Superficial Cerebral Astrocytoma Attached to Dura Report of Six Cases in Infants ANA LTA TARATUTO, MD,’.t JORGE MONGES, MD,t PEDRO LYLYK, M D , * t AND RAMON LEIGUARDA, MD*

Reported are six cases of meningocerebral astrocytomas attached to dura, involving the superficial cortex, in infants under 1 year of age. They represent 1.25% of 483 intracranial tumors in infancy studied at the Children’s Hospital in the last 12 years. Five were located in the frontal lobes, with variable extension to the parietal or the parietotemporal regions, and one was located in the parietal lobe. They were all composed of a solid portion and one or more cysts, and they measured approximately 6 to 12 cm in diameter. They had spindle cells, some more plump, arranged in areas in a storiform pattern. Tumors were very rich in reticulin fibers, mimicking a mesenchymal tumor. There was very slight pleomorphism. Bizarre giant cells were not observed and lipidization was not a prominent feature. Immunoperoxidase technique was performed in all of them and showed glial fibrillary acidic protein (GFAP) in most of the tumor cells. We believe their origin is from subpial astrocytes. They probably represent a separate entity whose diagnosis cannot be accurately established without immunohistochemical techniques. Cancer 54:2505-2512, 1984.

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hemispheric astrocytomas reported in large series of intracranial tumors in infants do not generally involve the leptomeninges.’-4Pleomorphic xanthoastrocytoma involving leptomeninges, but not the dura, has been recorded in young patients.’ Over the last 12 years, we have studied 483 intracranial tumors in infancy and childhood at the Children’s Hospital. Six of them (1.25%) were found to be meningocerebral tumors involving the superficial cortex and leptomeninges with attachment to the dura, in infants under 1 year of age. The tumors were very rich in reticulin fibers, mimicking a mesenchymal tumor of meningeal origin. Argentic techniques, as well as the Mallory phosphotungstic acid hematoxylin (PTAH), although suggesting the existence of some glial cells included in the reticulin network, did not reveal their histogenesis. However, the immunoperoxidase technique specific for glial fibrillary acidic protein (GFAP),6-9 clearly established their glial nature. We have found no UPRATENTORIAL

Presented in part at the IXth International Congress of Neuropathology, Vienna, September 5-10, 1982. From the *Institute de Investigaciones Neurologicas and the tDepartment of Neurosurgery, Children’s Hospital, Buenos Aires, Argentina. Supported in part by a grant from the Instituto Torcuato Di Tella. Address for reprints: Ana Lia Taratuto, MD, Ayacucho 2166, 1 112 Buenos Aim, Argentina. The authors thank Dr. Dons Dahl, PhD, for kindly providing the antiserum GFAP and also Mr. Luis Masciotra and Miss Alicia Sens for their technical assistance. Accepted for publication November 1 1 , 1983.

reference in the literature to similar cases in infants, with the exception of one reported by Bailey as “fibrosarcoma of the dura mater.”” We reported these cases because they probably represent a separate clinicopathologic entity. The findings are summarized in Table 1. Case Reports Case 1 A 6-month-old girl was born after an uncomplicated term pregnancy. Early development was normal. She was admitted to the hospital with a 1-month history of vomiting and imtability. A symmetric macrocephaly, bulging and tense fontanels, and forced downward deviation of the eyes (“sunset sign”) were found at physical examination. There was a mild increase in muscle tone in both lower limbs, with brisk reflexes. Skull x-rays showed separation of sutures, and computerized tomography (CT) scan revealed a huge cystic frontoparietal tumor with a solid portion, which showed postcontrast enhancement in the anteromedial frontal convexity. A left frontal craniotomy was performed. A mainly extracerebral mass, measuring approximately 11 cm in diameter, was found. The solid portion of the mass, which was firm and grayish in color, was attached to the dura and also in part to the inner table of the frontal bone and to the superior longitudinal sinus. The leptomeninges were included into the tumor, which was not clearly demarcated from the superficial cortex. The tumor had a big, deep, multiloculated cyst containing xanthocromic fluid. The tumor was dissected with the exception of a small anterior portion, which remained attached to the superior longitudinal sinus. The postoperative course

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TABLE1. Salient Clinical Features, CT Findings, Treatment, and Follow-Up from Patients with Superficial Cerebral Astrocytoma Attached to Dura Patient no. 1

Age (mo) 6

Sex

F

Clinical features

CT Findings

Treatment

Symmetric macrocephaly, bulging fontanels, “sunset sign”

Cystic left frontoparietal tumor with a solid post-contrastenhanced portion in the anteromedial frontal convexity Cystic right frontal tumor with a superficial anterolateral postcontrast-en hanced solid portion Cystic right frontoparietal tumor with a solid portion showing marked postcontrast-enhanced in the anterior frontal convexity Cystic right frontoparietotemporal tumor with a solid post-contrastenhanced portion in the superficial posteroinferior frontal region Cystic left frontoparietal tumor with a solid post-contrastenhanced portion in the posterolateral frontal convexity Cystic left parietofrontal tumor with a solid portion showing marked post-contrast enhancement

Subtotal excision (80%) Radiotherapy (4500 rad)

(5.5 yr) Normal

Subtotal excision (90%), Radiotherapy (5000 rad)

(3.5 yr) Normal development and normal neurologic examination

Subtotal excision (80%) Radiotherapy (3500 rad) Chemotherapy

(3.5 yr) Normal development and normal neurologic examination

Partial excision

Death immediately after surgery due to respiratory failure

2

6

F

Symmetric macrocephaly, bulging fontanels, “sunset sign”

3

6

M

Symmetric macrocephaly, bulging fontanels, “sunset sign,” spasticity and hyperactive reflexes in lower limbs

4

1.5

M

Asymmetric macrocephaly, bulging fontanels, ‘‘sunset sign,” left VI and VII cranial nerve palsy

5

6

7

9

M

F

Asymmetric macrocephaly, bulging fontanels

Asymmetric macrocephaly, bulging fontanels, “sunset sign,” spasticity and brisk reflexes in all four limbs

(50%)

FoIIOW-UP development and normal neurologic examination

VP shunt Subtotal excision Radiotherapy (5000 rad)

(1.5 yr) Normal

Total excision

(1 1 mo) Normal neurologic examination

development and normal neurologic examination

CT: computerized tomography; VP: ventnculorperitoneal.

was uneventful. She received radiation therapy (4500 rad). Five and one half years after surgery the patient is doing well and is symptom-free.

Case 2 A 6-month-old girl was admitted because of sporadic vomiting and progressive enlargement of the head. Since 1 week before admission, she had refused feeding. Her delivery had been uneventful. A symmetric macrocephaly, elevated pressure at the fontanels, diastasis of cranial sutures, “sunset sign,” and brisk reflexes in the lower extremities were found at physical examination. Skull x-rays revealed split sutures. CT scan showed a cystic right frontal tumor with a superficial anterolateral post-contrast-enhanced solid portion. At craniotomy, a large cystic and mainly extracerebral tumor approximately 13 cm in diameter was found. The tumor was firmly attached to the dura and consisted of a firm, almost rubbery, ivory-colored

portion and three cysts containing clear fluid. The tumor was dissected from the more normal-appearing tissue surrounding the lesion and almost totally removed. Following surgery, the patient received radiotherapy (5000 rad). Three and one half years after surgery, she is symptom-free and neurologic examination shows no abnormalities.

Case 3 A 6-month-old boy was brought to the hospital because of vomiting and progressive enlargement of the head during the last 3 months. His delivery had been uneventful. Physical examination showed a symmetric macrocephaly, bulging fontanels, and “sunset sign”; there was a mild spasticity with hyperactive reflexes on both lower limbs. Skull x-rays showed separation of sutures. CT scan revealed a large, cystic right frontoparietal tumor, with a solid portion showing marked postcontrast enhancement in the anterior frontal convexity

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(Fig. I). A right frontoparietal craniotomy was performed. The dura was tense and on opening it, a huge, rounded, and ivorycolored, mainly extracerebral mass, approximately 10 cm in diameter, with a deep, multiloculated cyst containing yellow fluid was found. The mass was firmly attached to the dura in the frontal region, involved the leptomeninges, and was not well demarcated from the surrounding cortex (Fig. 2). A subtotal excision (approximately 80%) of the mass was done. The postoperative course was uneventful. He received radiation therapy (3500 fad) and chemotherapy. Three and one half years after surgery, he is asymptomatic, and neurologic examination has revealed no abnormalities.

Case 4 A 40-day-old boy was delivered at term with a vertex presentation and low forceps extraction because of cephalopelvic disproportion. His mother had no history of illness, medication, or irradiation during the course of her pregnancy. At birth, it was noticed that he had a large head. Physical examination showed an asymmetric macrocephaly, elevated pressure at the fontanels, diastasis of cranial sutures, forced downward desviation of the eyes, and a left VI and VII nerve palsy. Skull x-rays revealed split sutures. CT scan showed a cystic right frontoparietotemporal tumor with a solid post-contrast-enhanced portion on the superficial posteroinferior frontal region. At craniotomy, a large, mainly extracerebral tumor attached to and invading the dura at the level of the pterion was found. The tumor measured approximately 12 cm in diameter and has a grayish and purplish solid portion, partially firm and partially spongy, and a big cyst, about 6 cm in diameter, with xanthocromic fluid. The leptomeninges were included into the tumor, which could not be well demarcated from the cortex. The tumor was only partially removed. Immediately after surgery, the patient had an acute respiratory failure and died.

FIG.2. Case 3. Macroscopic appearance of the tumor. The solid, firm, ivory-colored part of the tumor is attached to the dura (large arrow), involves the leptomeninges and seems to blend with the underlying superficial cortex (small arrow). There is no clear-cut demarcation between tumor and normal parenchyma. A part of a thin-walled cyst is shown in the upper part of the photograph.

Case 5

FIG. 1. Case 3. Postcontrast CT scan. Right frontopanetal tumor with a solid sumrficial portion showing - marked postcontrast enhancement and a big, deep cist.

A 7-month-old boy was delivered by Caesarean section because of abruption of placentae at the eighth month of pregnancy. His mother had no history of illness, medication, or irradiation during the course of her pregnancy. At birth he weighed 2600 g. Since the age of 1 month, his parents had noticed progressive enlargement of the head. CT scan done at another hospital showed a cystic mass on the left frontal region and hydrocephalus. A ventriculoperitoneal shunt was placed. A few days after shunting, he began to vomit and refused feeding, and was admitted to the Children’s Hospital. Physical examination showed an asymmetric macrocephaly, bulging and tense fontanels, and diastasis o f the cranial sutures. Otherwise, the examination was unremarkable. The shunt system was collapsed. CT Scan showed a cystic left frontoparietal tumor with a solid post-contrast-enhanced portion in the superficial posteroinferior frontal region. The angiogram revealed an avascular frontoparietal mass. At craniotomy, a huge mainly extracerebral tumor, measuring about 12 cm in diameter, was found. The solid portion of the tumor was grossly rubbery, avascular, and gray-white, and it involved the superficial cortex and the leptomeninges and was firmly attached to the dura. The adjacent skull was eroded. There was a big cyst

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FIGS. 3A-3C. Case 1. Extracerebral main mass of the tumor. Spindle-shaped cells arranged in fascicles intermingled with reticulin proliferation. GFAP strong positivity is observed in most of the tumor cells (A, top left: H & E, original magnification XIOO; B, top right: Gomori’s reticulin, original magnification X 100; C, bottom left GFAP, original magnification X 100).

deep to the solid portion. This part of the tumor seemed to blend with the underlying brain, from which it could not be easily differentiated. The tumor was almost totally resected and the shunt removed. He received radiotherapy (5000 rad). One and one half years after surgery, the patient is symptomfree, and has had normal development.

tumor was totally removed. She recovered well from surgery and did not receive postoperative irradiation or chemotherapy. Eleven months after surgery she is asymptomatic and examination shows no abnormalities.

Case 6

In all six cases the tumor was supratentorial. The frontal lobe was preferentially involved; five of the tumors were located in the frontal lobe and had variable extension to the adjacent lobes. Only one seems to involve mainly the parietal lobe. All of the tumors were huge and superficial, mainly extracerebral tumors, measuring approximately 10 to 13 cm in diameter, involving the cortex and the leptomeninges, and firmly attached to the dura. In one case there was also operative evidence of erosion of the inner table of the adjacent skull. All of the tumors were composed of a solid and a cystic portion. The solid superficial portion of the tumors was grossly described as an ivory-colored or gray and white, avascular, firm, and sometimes rubbery mass. None of the cases showed gross evidence of necrosis. This part of the tumors did not have a clear-cut demar-

A 9-month-old girl was admitted to the hospital with a 1month history of vomiting and progressive somnolience. Her delivery and early development had been normal. At examination she was found to be stuporous, and had a symmetric macrocephaly, bulging fontanels, forced downward desviation of the eyes, spasticity, and increased reflexes in all four limbs. CT scan showed a left cystic panetofrontal lesion with a solid superficial and parietal portion, which enhanced markedly. The cyst was punctured, and 30 cm3 of a xanthocromic fluid were evacuated. A large craniotomy was performed. The dura was tense, and on opening it, a huge superficial tumor of approximately 10 cm in diameter was found. There was a cyst deep to the surface. The solid portion of the tumor was attached to the dura, involved the leptomeninges and the superficial cortex, and was firm and ivory-colored. Grossly, it was somewhat demarcated from the surrounding brain. The

Location and Macroscopic Appearance of the Tumor

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FIGS. 4A-4C. Case 3. (A, top left) Tumor cells small gemistocytes strongly positive for GFAP (GFAP, original magnification X400). (B, top right) Glial cells with long processes intermingled with reticulin fibers (GFAP, original magnification X400). (C, bottom left) Area attached to dura. GFAP strongly positive cells in the midst of connective tissue (GFAP, original magnification X400).

cation from the surrounding cortex, and in most of the cases seemed to blend with the adjacent brain. None of the tumors appeared as to be encapsulated. The cysts were uni- or multiloculated, they contained clear, yellow, or xanthocromic fluid and, in all of the cases, were located deep to the solid part of the tumors.

Methods All of the specimens were fixed in formaldehyde 10% and embedded in paraffin. The following stains were used: hematoxylin and eosin and periodic acid-Schiff (Mc Manus), Mallory’s PTAH, Gomori’s reticulin, and Mallory’s trichrome. Frozen sections from the formaldehyde-fixed specimens were stained with Sudan 111 and IV. Sternberger’simmunoperoxidase technique for GFAP was performed in paraffin-embedded sections, in accordance with previously published techniques. Control sections using normal rabbit serum or phosphate-buffered saline (PBS) instead of specific antiserum were performed. Postfixation in osmic acid and Epon embedding (Epon 812 [Fluka A. G. Buchs, Switzerland]) was performed

’’

in two cases. One-micron sections were stained with toluidine blue for light microscopic examination. Thin sections were stained with uranyl acetate and lead citrate and were examined under the Siemens Elmiskop 101 electron microscope.

Microscopic Findings In the extracerebral main mass of the tumor, spindleshaped cells were arranged in fascicles, or in a whorled or storiform patterns intermingled with very prominent reticulin proliferation (Figs. 3A and 3B). Some areas exhibited plumper tumor cells, and small gemistocytes were observed in 50% of the cases. (Fig. 4A) GFAP strong positivity was observed in most of the tumor cells (Fig. 3C). Very few GFAP-negative cells seemed to be fibroblasts. Bizarre giant cells, an increase in mitotic activity, or necrosis were not observed. Glial processes positive to GFAP antiserum could be seen intermingled with reticulin fibers (Fig. 4B). In few areas there was an increase in cellularity, slight pleomorphism, and less reticulin. Some cysts lined by GFAP-positive cells were observed. Lipidization was not a prominent feature,

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FIGS.5A AND 5B. Case 4. (A, left) Astrocytic proliferation is seen on the superficial cortex. (small arrow) Tongues of loosely cellular and fibrillary GFAP-positive matrix extending from the cortex into leptomeninges are also observed (large arrow); these can be followed far from the brain surface. GFAP-positive cells are also seen in the leptomeninges and in the extracerebral main mass of the tumor (GFAP, original magnification X 100). (B,right) Reticulin proliferation in leptomeninges and in the tumor mass. (arrow points to the superficial cortex) (Gomori’s reticulin, original magnification X 100).

although tiny vacuoles were observed in few isolated cells in two cases. In areas immediately attached to dura, there were fewer GFAP-positive glial cells and more connective tissue (Fig. 4C). Focal lymphocytic infiltration was present. Superficial cortex was included in all biopsy specimens (Figs. 5A and 5B). GFAPpositive tumor cells surrounded by reticulin fibers were observed within Virchow-Robin spaces. Superficial cortical areas next to leptomeninges showed astrocytic proliferation. Small gemistocytes were also observed. Among these there were some cells with scanty cytoplasm. In two cases, microcysts were present focally in superficial cortex, and in one of these cases part of a big cyst lined by GFAP-positive cells was also observed. In three cases, tongues of loosely cellular (astrocytes) and fibrillary GFAP-positive matrices were observed, extending from the cortex into leptomeninges, and they could even be followed far from the brain surface in the midst of the reticulin proliferation, which was intermingled with GFAP-positive cells. Gemistocytes could also be followed from the cortex into leptomeninges in the other three cases. Electron microscopy was performed on formalin-fixed specimens from two cases and revealed the presence of intracytoplasmatic filaments in tumor cells as well as a surrounding basal lamina (Fig. 6). Discussion We have described six cases of intracranial tumors with almost identical clinical and pathologic features. All patients were under 1 year of age and presented with symmetrical or assymetrical macrocephaly, together

with other signs of increased intracranial pressure without focal neurologic deficit, except for one case. In none was the diagnosis clinically suspected. CT findings were impressive and very similar in all cases, and the prognosis following surgical excision, either total or partial, and radiotherapy seems quite favorable. These big tumors, predominantly located in the frontal lobes, were solid and cystic. All involved the superficial cortex and the leptomeninges and were firmly attached to the dura. The strong GFAP immunostaining gave unequivocal support to the glial nature of the tumor cells. Although the main mass of the tumors was extracerebral, grossly mimicking a leptomeningeal tumor, superficial cortex was involved in every case, and profound cysts were also observed in CT brain scanning and at surgery. Even though astrocyte proliferation in the superficial layer of cortex does not seem to be that of a conventional astrocytoma, and some cells could also be reactive, we believe they represent the intracerebral component of these tumors. Tongues of loosely cellular and fibrillary GFAP-positive matrices extending from the cortex into leptomeninges, as well as small gemistocytes that could be followed from the cortex into leptomeninges, are in agreement with this statement. Small microcysts present focally in superficial cortex in areas of loosely astrocytic proliferation give it further support. Thus, we do not believe that these tumors are extracerebral leptomeningeal astrocytomas12-16like those described, mostly in adults in the fourth decade of life, arising from heterotopic glial Prominent reticulin proliferation was observed intermingled with the

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FIG.6. Case 3. Electron micrograph shows tumor cells surrounded by basal lamina (original magnification X 18,000). Inset: basal lamina (arrows) at higher power (original magnification X32,OOO).

tumor cells in Virchow-Robin spaces and leptomeninges up to the dura. It is a well-known fact that reactive connective tissue proliferation is to be found whenever the leptomeninges are invaded by gliomas, presenting a pattern that results from the alignment of the tumor cells within the interfibrillary spaces.” Mixed glioma-sarcoma, resulting from the acquisition of neoplastic properties by the meningeal cells, can be observed, although this seldom occurs. We found neither increased mitotic activity, severe pleomorphism necrosis, nor any other strong evidence favoring this diagnosis in our cases. Furthermore, we observed intermingling of glial cells and connective tissue rather than the marmorate pattern, as it has been described, in mixed glioma-sarcoma.20 The main differences from xanthoastrocytomas5 lay in that our cases were attached to dura, there was very slight pleomorphism, bizarre giant cells were not observed, and lipidization was not a prominent feature. On the other hand, the original report on xanthoastrocytomas referred to patients aged between 7 and 25 years old (average, 12.4 years), whereas our patients are infants younger than 1 year of age. Therefore, our patients do not have any resemblance to those previously described, with the exception, perhaps, of Case 3 reported by Bailey in 1945” as “Intracranial fibrosarcoma of the dura mater in childhood.” The origin of these tumors may be subject to speculation. However, we believe, as has been postulated with xanthoastrocytomas, that they originate from superficially

located cortical astrocytes. The existence of an envelope or basal lamina covering the surface of the cell, as observed in two cases in which ultrastructural studies were performed, is further evidence in favor of this hypothesis. Reticulin may in part represent this basal lamina, but a strong desmoplastic reaction secondary to leptomeningeal invasion and dural attachment may also be considered responsible. These cases resembled each other in their clinical, gross, and microscopic aspects, which led us to postulate that they constitute a separate clinicopathologic entity probably hitherto unrecognized. Their diagnosis cannot be accurately established without immunohistochemical techniques. REFERENCES 1. Heiskanen 0. Intracranial tumors in children. Childs Bruin 1977; 369-78. 2. Hooper R. Intracranial tumors in children. Childs Bruin 1975; 1: 136- 140. 3. Mercuri S, Russo A, Palma L. Hemispheric supratentorial astrocytomas in children. J Neurosurg 1981; 55:170-173. 4. Pedersen H, Gjenis F, Klinken L. Computed tomography of benign supratentorial astrocytomas of infancy and childhood. Neuroradiology 1981; 21:87-91. 5. Kepes JJ, Rubinstein U, Eng LF. Pleomorphic xanthoastrocytoma: A distinctive meningocerebral glioma of young subjects with relatively favorable prognosis. A study of i 2 cases. Cancer 1979; 55:170-173. 6. Bignami A, Dahl D, Rueger DC. Glial fibrillary acidic protein (GFA) in normal cells and in pathological conditions. In: Advances in Cell Neurobiology, vol 1. New York Academic Press, 1980 1:285310. 7. De Armond SJ, Eng LF, Rubinstein LJ. The application of glial

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fibrillary acidic (GFA) protein immunohistochemistry in neuro-oncology: A progress report. Puthol Res Pract 1980; 168:374-394. 8 . Duffy PE, Graf L, Rapport MM. Identification of glial fibrillary acidic protein by the immunoperoxidase method in human brain tumors. J Neuropathol Exp Neurol 1977; 36:645-652. 9. Eng LF, Vanderhaeghen JJ, Bignami A, Gerstl B. An acidic protein isolated from fibrous astrocytes. Bruin Res 1971; 28:35 1-354. 10. Bailey OT, Ingraham FD. Intracranial fibrosarcomasof the dura mater in childhood. J Neurosurg 1945; 2: 1-1 5. 11. Deck JHN, Eng LF, Bigbee J, Woodcock SM. The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors. Acta Neuropathol 1978; 42:183-190. 12. Abbot KH, Glass B. Intracranial extracerebral (leptomeningeal glioma) In: Proceedings of the 2nd International Congress of Neuropathology. Part I: Amsterdam: Excerpta Medica, 1955; 165. 13. Bailey OT. Relation of glioma of leptomeninges to neuroglia nests: Report of a case of astrocytoma of leptomeninges. Arch Puthol 1936; 21584-600.

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14. Daum S, LeBeau J, Billet B. GIiomes sustentoriels a development extracerebral. Neurochirurgie 1963; 9:279-288. 15. Horoupian DS, Lax F, Suzuki K. Extracerebral leptomeningeal astrocytoma mimicking a meningioma. Arch Pathol Lab Med 1979; 1031676-679. 16. Sumi SM, Leffman H. Primary intracranial leptomeningeal glioma with persistent hypoglycorrhachia. J Neurol Neurosurg Psychiatr 1968; 3 1: 190-194. 17. Brun A. Marginal glioneuronal heterotopias of the central nervous system. Acta Pathol Microbiol Scand 1965; 65:221-233. 18. Cooper IS, Kernohan JW. Heterotopic glial nests in the subarachnoid space: Histopathologic characteristics, mode of origin and relation to meningeal gliomas. J Neuropathol Exp Neurol 1951; 101629. 19. Russell DS, Rubinstein W. Pathology of tumors of the nervous system. Edward Arnold Publishers, Ltd., 1977; 337. 20. Rubinstein LJ. The development of contiguous Sarcomatous tissue in intracranial tumors. J Pathol Bacteriol 1956; 7 1:441-459.

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