202
Surg Neural 1991 ;36 :202-6
Cerebral Granular Cell Tumor Occurring with Glioblastoma Multiforme: Case Report Cheryl P . Harris, M .D., Jeannette J . Townsend, M .D., Douglas L . Brockmeyer, M .D., and M . Peter Heilbrun, M .D. Department of Pathology and the Division of Neurosurgery, University of Utah Medical Center, Salt Lake City, Utah
Harris CP, Townsend JJ, Brockmeyer DL, Heilbrun MP . Cerebral granular cell tumor occurring with glioblastoma multiforme : case report. Surg Neurol 1991 ;36 :202-6 . A 65-year-old man presented with 4 weeks of partial right visual field loss . A left occipital granular cell tumor was diagnosed via open biopsy . No specific tumoricidal therapy was given, and the patient returned 2 weeks later with fluent dysphasia and mild right hemiparesis, and formed visual hallucinations . A large left parietotemporal mass, separate from the granular cell tumor, was diagnosed as a glioblastoma multiforme by stereotactic biopsy . The histogenesis of cerebral granular cell tumors is controversial ; this case supports recent speculation of their possible glial origin . Granular cell rumor ; Glioblastoma multiforme ; Immunohistochemistry KEY WORDS :
Granular cell tumors are common soft tissue tumors found in the tongue, respiratory tract, skin, breast, and subcutaneous tissue [8] . Their presence in the central nervous system (CNS) is uncommon ; they have been described in the pituitary gland ("choristoma") [2,5], cranial nerves [121, and cerebral hemispheres [3,7,9, 11,14,17] . The histogenesis of both systemic and CNS granular cell tumors is controversial . Originally called "granular cell myoblastomas" by Abrikossoff [1] in 1926, they were thought to be derived from muscle cells . More recent studies have provided evidence in favor of a Schwann cell [4,6,13,15] or glial origin [3,11,14] . We describe a man with a cerebral granular cell tumor who later developed a glioblastoma multiforme in a nearby location, thus supporting the theory that cerebral granular cell tumors might arise from glial precursors .
Address reprint requests to : Cheryl P . Harris, M .D ., Department of Pathology, University of Utah Medical Center, 50 North Medical Drive, Salt lake City, Utah 84132 . Received October 22, 1990 ; accepted December 19, 1990 .
co 1991 by Elsevier Science Publishing Cu., Inc .
Case Report A 65-year-old left-handed man had 4 weeks of progressive right visual field loss associated with mild left temporal headaches and fatigue. Neurologic examination showed mild word-finding difficulty and a partial right homonymous hemianopia . Computed tomography (CT) scan demonstrated a left occipital enhancing mass associated with moderate edema and a 3-mm left-to-right midline shift (Figure 1) . A biopsy of the mass via a left occipital craniotomy was performed . Histopathologic examination established the diagnosis of granular cell tumor (described in detail below) . Neither chemotherapy nor radiation therapy was instituted . The patient did well until 2 weeks later, when he noted progressive speech difficulties and formed visual hallucinations. Neurologic examination showed a moderate anomic dysphasia, an incomplete right homonymous hemianopia, and a left Horner's syndrome . There was a mild right central seventh nerve paresis, and mild right hemiparesis associated with hyperreflexia and an extensor plantar responseA repeat CT scan showed a separate ring-enhancing lesion (4 cm') in the left temporal lobe, with marked edema and mass effect (Figure 2) . The granular cell tumor was slightly larger, with less enhancement than observed previously . T2-weighted magnetic resonance imaging confirmed two separate lesions : one in the left temporal area and the other in the left occipital lobe (Figure 3) . Stereotactic biopsy of the left temporal lobe mass was carried out, and histopathologic examination of the biopsy specimen showed glioblastoma multiforme, described in detail below . Whole brain radiation therapy of 5690 rad with tumor bed boost to the left temporal area and adjunctive chemotherapy were administered . After therapy, the granular cell tumor remained stable in both size and amount of radiographic enhancement . The glioblastoma, despite initial favorable clinical and radiographic response, eventually recurred and caused the patient's death 12 months 0090-3019/91/$3 .50
Surg Neurol 1991 ;36 :202-6
Granular Cell Tumor and Glioblastoma
Figure
20 3
3 . Magnetic resonance image (T2-weighted image) revealing separate lesions in the left hemisphere .
Figure
o
1 . A CT scan with enhancement showing the left occipital lobe
lesion.
after its diagnosis . Permission to perform an autopsy was refused .
Figure
2 . A CT scan with enhancement showing a ring-enhancing lesion in the left temporal lobe associated with marked edema and a, midline shift . The granular cell tumor in the occipital lobe has increased .lightly .
Neuropathology Microscopic examination of hematoxylin and eosinstained sections of the granular cell tumor showed sheets of large polygonal or rounded cells contiguous with neighboring cells (Figure 4) . Small central nuclei predominated, but a moderate degree of pleomorphism was seen ; there were scattered nucleoli present . Mitotic figures and necrosis were absent . Although relatively well circumscribed, there were isolated areas of invasion of adjacent brain . The cytoplasm contained coarse, periodic acid-Schiff (PAS) granules (Figure 5), which did not digest with PAS-diastase . Immunohistochemical studies showed that the granular cells did not express S-100 protein . Faint immunoreactive staining was detected with both glial fibrillary acidic protein (GFAP) and neuron-specific enolase . Markers for macrophages (Mac 387) and keratin were negative . The tumor did not stain with Sudan black . Histopathologic examination of the second tumor showed features typical of a glioblastoma multiforme . Marked nuclear pleomorphism (Figure 6) and moderate numbers of mitotic figures were seen . There were several multinucleated cells and large areas of necrosis present ; the cells expressed GFAP . There were no granular cells in the left temporal biopsy specimen .
204
Neurol 1991 ;36 :202-6 Surg
Harris et al
Figure 4. Granular cell tumor (hematoxylin and
eosin x 131) .
Discussion A primary cerebral granular cell tumor was first reported by Markesbery et al [11] in 1973 . Since then, several other CNS granular cell tumors have been described [3,7,9,10,14,17], though they remain less common than their systemic counterparts . There has been only one previous report of a granular cell tumor coexisting with a malignant astrocytoma 19] . Several theories exist concerning the histogenesis of both systemic and CNS granular cell tumors . Granular cell tumors were first described in 1926 by Abrikossoff [11, who felt they were derived from skeletal muscle .
Figure 5 . Granular cell tumor (periodic acidSchiff x 1400) .
Few authors today, however, believe that these tumors are of muscle origin . A Schwann cell origin theory of systemic granular cell tumors, first proposed by Fust and Custer [6] in 1949, is suggested by the markedly positive 5-100 immunoreactivity shared by normal Schwann cells and systemic granular tumor cells [15] . Central nervous system granular cell tumors in several reports [3,71 and in the current case, however, have been S-100 negative . This reinforces the concept of inherent differences between systemic and CNS granular cell tumors, and has caused continued speculation concerning the histogenesis of cerebral granular cell tumors. In their description of a third ventricular granular cell
Granular Cell Tumor and Glioblastoma
Surg Neurol 1991 ;36 : 2 0 2 -6
205
Figure 6. Glioblastoma multiforme (hematoxylin and eosin x 131) .
tumor, Hori et al [7] suggested a mesenchymal histogenesis due to demonstration of vimentin intermediate filaments. Though vimentin is expressed in cells of mesenchymal origin, the protein is not specific for mesenchyme [16] . Vimentin intermediate filaments, however, were not present in the cerebral granular cell tumor reported by Dickson et al [3] . Several investigators have suggested a glial origin for cerebral granular cell tumors . Sakurama et al [14] and Ule et al [ 17], in a combined total of three cases, demonstrated glial filaments in the granular cells by immunohistochemical and ultrastructural means . The cases described by Dickson et al [3], Kornfeld [9], and the present study demonstrated focal areas of GFAP expression of cerebral granular tumor'cells . The cases of Kornfeld [9] consisted of two CNS tumors with interdigitated granular cells and neoplastic
astrocytes . He named these tumors granular cell glioblastomas and felt that the granular cells were transformed neoplastic astrocytes based on the focal areas of GFAP expression in the granular cells . Our case differed from Kornfeld's in that, by radiographic and biopsy evidence, the granular tumor cells and the malignant astrocytes seemed to be separate . The possibility of a microcellular connection between the two tumors still exists, however . Unfortunately, this could not be determined, as we were unable to obtain permission for an autopsy . Nine cerebral granular cell tumors (other than those arising from the adenohypophysis) have been reported, and a review of the treatment of these tumors is presented in Table 1 . In seven of the nine cases, the tumors were subtotally or completely resected . Two of the tumors were biopsied only . After surgery, several of the
Table 1 . Treatment of Reported Cerebral Granular Cell Tumors Author Markesbery et al [11] Sakurama et al [ 14] Lechevalier et at [10] Hori et al [7] Dickson et al [3) Kornfeld [9) Present case (1991)
Surgical treatment
Radiation therapy
Parietal region Corpus callosum Frontal
Subtotal resection Partial resection Subtotal resection
5000 tad 5000 rad
Parietooccipital Third ventricle Frontal
Partial resection
Temporoparietal°
Biopsy
Ftontoparietala Occipirals Temporal`
Partial resection
Tumor location
Designates a granular cell glioblastoma . "Designates the granular cell tumor . `Designates the glioblastoma.
Complete excision
Subtotal resection Biopsy Biopsy
Amount not specified 6300 rad None 4560 rad None 6000 rad 5690 rad
Chemotherapy None
None None None None None None None -
Carmustine
Survival after diagnosis 17 months 12 months 24 months 11 months 6 days postop
Not available 2 months 8 months 12 months 12 months
206
Surg Neurol 1991 ;36 :202-6
patients displayed transient improvement in neurological symptoms . Radiation therapy was employed in six cases and did not prolong survival in five of the patients [9-11,14], though radiation was directed toward the malignant astrocytoma in the present case . To date, there is no specific chemotherapy for systemic or CNS granular cell tumors . Antineoplastic agents directed to the astrocytic tumor in our case did not seem to influence the biologic behavior of the granular cell tumor. A review of recent evidence [12] suggests that a complex, multistep accumulation of mutations is responsible for malignant cell transformation . It is conceivable that cerebral granular cell tumors and glioblastomas are different manifestations of transformed glial precursors, with each tumor expressing a unique combination of mutagenic events . In conclusion, the debate surrounding the origin of cerebral granular cell tumors is still not settled . The association of granular cell tumor with glioblastoma multiforme remains difficult to explain . The available evidence seems to suggest that cerebral granular cell tumors may arise from glial precursors, and, therefore, when a granular cell tumor occurs in the brain, the possibility of a coexisting malignant glioma should be considered . The authors would like to thank Dr . Dan W . Fults for editorial assistance and Keith E . Johnson for photographic assistance .
References 1 . Abrikossoff A . Uber Myome, ausgehend van der quergestreiften willkurlichen Muskulatur . Virchows Arch [A) 1926 ;260 :215-33 . 2 . Becker DH, Wilson CB . Symptomatic parasellar granular cell tumors . Neurosurgery 1981 ;8 :173-80 .
Harris et al
3 . Dickson DW, Suzuki KI, Kanner R, Weitz S, Horoupian DS . Cerebral granular cell tumor : immunohisrochemical and electron microscopic study. J Neuropathol Exp Neurol 1986 ;45 :304-14 . 4 . Fisher ER, Wechsler H . Granular cell myoblastoma : a misnomer : electron microscopic and histochemical evidence concerning its Schwann cell derivation and nature . Cancer 1962 ;15 :936-54 . 5 . Friede RL, Yasargil MG . Suprasellar neoplasm with agranular cell component . J Neuropathol Exp Neurol 1977 ;36 :769-82 . 6 . Fust JA, Custer RP . On the neurogenesis of so-called granular cell myoblastoma. Am J Clin Partial 1949 ;19:522-35 . 7 . Hori A, Altmannsberger M, Spoerri 0, Beuche W . Granular cell tumour in the third ventricle . Acta Neurochir (Wien) 1985 ;74 :49-52 . 8 . Khansur T, Balducci L, Tavassoli M . Granular cell tumor : clinical spectrum of the benign and malignant entity . Cancer 1987 ; 60 :220-2 . 9 . Kornfeld M . Granular cell glioblasmma : a malignant granular cell neoplasm of astrocytic origin . J Neuropathol Exp Neurol 1986;45 :447-62 . 10 . Lechevaher B, Mandard JC, Adam Y, Da Silva DC, Bazin C, Courtheoux P . Tumeur a cellules granuleuses d'un hemisphere cerebral : interet de la recherche de Ia proreine acidegliofibrillaire . Rev Neurol (Paris) 1982 ;138 :619-29 . 11 . Markesbery WR, Duffy PE, Cowen D . Granular cell rumors of the central nervous system . J Neuropathol Exp Neurol 1973 ; 32 :92-109 . 12 . Marx J . Many gene changes found in cancer. Science 1989 ; 246 :1386-8 . 13 . RaoTV, Puri R, ReddyGNN . Intracranial trigeminalnervegranular cell myoblasroma: case report . J Neurosurg 1983 ;59 :706-9 . 14 . Sakurama N, Matsukado Y, Marubayashi T, Kodama T . Granular cell tumor of the brain and its cellular identity . Acta Neurochir (Wien) 1981 ;56 :81-94 . 15 . Stefansson K, Wollmann RL. S-100 protein in granular cell tumors . Cancer 1982 ;49 :1834-8 . 16 . Traub P . Intermediate neurofilaments . Berlin: Springer, 1985 : 14-517 . Ule G, Tschahargane C, Haag D, Berlet H, Volk B . Maligner granular-zelltumor des Grofihirnmarkes . Acta Neuropathol (Berl) 1975 ;32 :143-55 .
Surg Neural 1991 ;36 :202-6
Cerebral Granular Cell Tumor Occurring with Glioblastoma Multiforme: Case Report Cheryl P . Harris, M .D., Jeannette J . Townsend, M .D., Douglas L . Brockmeyer, M .D., and M . Peter Heilbrun, M .D. Department of Pathology and the Division of Neurosurgery, University of Utah Medical Center, Salt Lake City, Utah
Harris CP, Townsend JJ, Brockmeyer DL, Heilbrun MP . Cerebral granular cell tumor occurring with glioblastoma multiforme : case report. Surg Neurol 1991 ;36 :202-6 . A 65-year-old man presented with 4 weeks of partial right visual field loss . A left occipital granular cell tumor was diagnosed via open biopsy . No specific tumoricidal therapy was given, and the patient returned 2 weeks later with fluent dysphasia and mild right hemiparesis, and formed visual hallucinations . A large left parietotemporal mass, separate from the granular cell tumor, was diagnosed as a glioblastoma multiforme by stereotactic biopsy . The histogenesis of cerebral granular cell tumors is controversial ; this case supports recent speculation of their possible glial origin . Granular cell rumor ; Glioblastoma multiforme ; Immunohistochemistry KEY WORDS :
Granular cell tumors are common soft tissue tumors found in the tongue, respiratory tract, skin, breast, and subcutaneous tissue [8] . Their presence in the central nervous system (CNS) is uncommon ; they have been described in the pituitary gland ("choristoma") [2,5], cranial nerves [121, and cerebral hemispheres [3,7,9, 11,14,17] . The histogenesis of both systemic and CNS granular cell tumors is controversial . Originally called "granular cell myoblastomas" by Abrikossoff [1] in 1926, they were thought to be derived from muscle cells . More recent studies have provided evidence in favor of a Schwann cell [4,6,13,15] or glial origin [3,11,14] . We describe a man with a cerebral granular cell tumor who later developed a glioblastoma multiforme in a nearby location, thus supporting the theory that cerebral granular cell tumors might arise from glial precursors .
Address reprint requests to : Cheryl P . Harris, M .D ., Department of Pathology, University of Utah Medical Center, 50 North Medical Drive, Salt lake City, Utah 84132 . Received October 22, 1990 ; accepted December 19, 1990 .
co 1991 by Elsevier Science Publishing Cu., Inc .
Case Report A 65-year-old left-handed man had 4 weeks of progressive right visual field loss associated with mild left temporal headaches and fatigue. Neurologic examination showed mild word-finding difficulty and a partial right homonymous hemianopia . Computed tomography (CT) scan demonstrated a left occipital enhancing mass associated with moderate edema and a 3-mm left-to-right midline shift (Figure 1) . A biopsy of the mass via a left occipital craniotomy was performed . Histopathologic examination established the diagnosis of granular cell tumor (described in detail below) . Neither chemotherapy nor radiation therapy was instituted . The patient did well until 2 weeks later, when he noted progressive speech difficulties and formed visual hallucinations. Neurologic examination showed a moderate anomic dysphasia, an incomplete right homonymous hemianopia, and a left Horner's syndrome . There was a mild right central seventh nerve paresis, and mild right hemiparesis associated with hyperreflexia and an extensor plantar responseA repeat CT scan showed a separate ring-enhancing lesion (4 cm') in the left temporal lobe, with marked edema and mass effect (Figure 2) . The granular cell tumor was slightly larger, with less enhancement than observed previously . T2-weighted magnetic resonance imaging confirmed two separate lesions : one in the left temporal area and the other in the left occipital lobe (Figure 3) . Stereotactic biopsy of the left temporal lobe mass was carried out, and histopathologic examination of the biopsy specimen showed glioblastoma multiforme, described in detail below . Whole brain radiation therapy of 5690 rad with tumor bed boost to the left temporal area and adjunctive chemotherapy were administered . After therapy, the granular cell tumor remained stable in both size and amount of radiographic enhancement . The glioblastoma, despite initial favorable clinical and radiographic response, eventually recurred and caused the patient's death 12 months 0090-3019/91/$3 .50
Surg Neurol 1991 ;36 :202-6
Granular Cell Tumor and Glioblastoma
Figure
20 3
3 . Magnetic resonance image (T2-weighted image) revealing separate lesions in the left hemisphere .
Figure
o
1 . A CT scan with enhancement showing the left occipital lobe
lesion.
after its diagnosis . Permission to perform an autopsy was refused .
Figure
2 . A CT scan with enhancement showing a ring-enhancing lesion in the left temporal lobe associated with marked edema and a, midline shift . The granular cell tumor in the occipital lobe has increased .lightly .
Neuropathology Microscopic examination of hematoxylin and eosinstained sections of the granular cell tumor showed sheets of large polygonal or rounded cells contiguous with neighboring cells (Figure 4) . Small central nuclei predominated, but a moderate degree of pleomorphism was seen ; there were scattered nucleoli present . Mitotic figures and necrosis were absent . Although relatively well circumscribed, there were isolated areas of invasion of adjacent brain . The cytoplasm contained coarse, periodic acid-Schiff (PAS) granules (Figure 5), which did not digest with PAS-diastase . Immunohistochemical studies showed that the granular cells did not express S-100 protein . Faint immunoreactive staining was detected with both glial fibrillary acidic protein (GFAP) and neuron-specific enolase . Markers for macrophages (Mac 387) and keratin were negative . The tumor did not stain with Sudan black . Histopathologic examination of the second tumor showed features typical of a glioblastoma multiforme . Marked nuclear pleomorphism (Figure 6) and moderate numbers of mitotic figures were seen . There were several multinucleated cells and large areas of necrosis present ; the cells expressed GFAP . There were no granular cells in the left temporal biopsy specimen .
204
Neurol 1991 ;36 :202-6 Surg
Harris et al
Figure 4. Granular cell tumor (hematoxylin and
eosin x 131) .
Discussion A primary cerebral granular cell tumor was first reported by Markesbery et al [11] in 1973 . Since then, several other CNS granular cell tumors have been described [3,7,9,10,14,17], though they remain less common than their systemic counterparts . There has been only one previous report of a granular cell tumor coexisting with a malignant astrocytoma 19] . Several theories exist concerning the histogenesis of both systemic and CNS granular cell tumors . Granular cell tumors were first described in 1926 by Abrikossoff [11, who felt they were derived from skeletal muscle .
Figure 5 . Granular cell tumor (periodic acidSchiff x 1400) .
Few authors today, however, believe that these tumors are of muscle origin . A Schwann cell origin theory of systemic granular cell tumors, first proposed by Fust and Custer [6] in 1949, is suggested by the markedly positive 5-100 immunoreactivity shared by normal Schwann cells and systemic granular tumor cells [15] . Central nervous system granular cell tumors in several reports [3,71 and in the current case, however, have been S-100 negative . This reinforces the concept of inherent differences between systemic and CNS granular cell tumors, and has caused continued speculation concerning the histogenesis of cerebral granular cell tumors. In their description of a third ventricular granular cell
Granular Cell Tumor and Glioblastoma
Surg Neurol 1991 ;36 : 2 0 2 -6
205
Figure 6. Glioblastoma multiforme (hematoxylin and eosin x 131) .
tumor, Hori et al [7] suggested a mesenchymal histogenesis due to demonstration of vimentin intermediate filaments. Though vimentin is expressed in cells of mesenchymal origin, the protein is not specific for mesenchyme [16] . Vimentin intermediate filaments, however, were not present in the cerebral granular cell tumor reported by Dickson et al [3] . Several investigators have suggested a glial origin for cerebral granular cell tumors . Sakurama et al [14] and Ule et al [ 17], in a combined total of three cases, demonstrated glial filaments in the granular cells by immunohistochemical and ultrastructural means . The cases described by Dickson et al [3], Kornfeld [9], and the present study demonstrated focal areas of GFAP expression of cerebral granular tumor'cells . The cases of Kornfeld [9] consisted of two CNS tumors with interdigitated granular cells and neoplastic
astrocytes . He named these tumors granular cell glioblastomas and felt that the granular cells were transformed neoplastic astrocytes based on the focal areas of GFAP expression in the granular cells . Our case differed from Kornfeld's in that, by radiographic and biopsy evidence, the granular tumor cells and the malignant astrocytes seemed to be separate . The possibility of a microcellular connection between the two tumors still exists, however . Unfortunately, this could not be determined, as we were unable to obtain permission for an autopsy . Nine cerebral granular cell tumors (other than those arising from the adenohypophysis) have been reported, and a review of the treatment of these tumors is presented in Table 1 . In seven of the nine cases, the tumors were subtotally or completely resected . Two of the tumors were biopsied only . After surgery, several of the
Table 1 . Treatment of Reported Cerebral Granular Cell Tumors Author Markesbery et al [11] Sakurama et al [ 14] Lechevalier et at [10] Hori et al [7] Dickson et al [3) Kornfeld [9) Present case (1991)
Surgical treatment
Radiation therapy
Parietal region Corpus callosum Frontal
Subtotal resection Partial resection Subtotal resection
5000 tad 5000 rad
Parietooccipital Third ventricle Frontal
Partial resection
Temporoparietal°
Biopsy
Ftontoparietala Occipirals Temporal`
Partial resection
Tumor location
Designates a granular cell glioblastoma . "Designates the granular cell tumor . `Designates the glioblastoma.
Complete excision
Subtotal resection Biopsy Biopsy
Amount not specified 6300 rad None 4560 rad None 6000 rad 5690 rad
Chemotherapy None
None None None None None None None -
Carmustine
Survival after diagnosis 17 months 12 months 24 months 11 months 6 days postop
Not available 2 months 8 months 12 months 12 months
206
Surg Neurol 1991 ;36 :202-6
patients displayed transient improvement in neurological symptoms . Radiation therapy was employed in six cases and did not prolong survival in five of the patients [9-11,14], though radiation was directed toward the malignant astrocytoma in the present case . To date, there is no specific chemotherapy for systemic or CNS granular cell tumors . Antineoplastic agents directed to the astrocytic tumor in our case did not seem to influence the biologic behavior of the granular cell tumor. A review of recent evidence [12] suggests that a complex, multistep accumulation of mutations is responsible for malignant cell transformation . It is conceivable that cerebral granular cell tumors and glioblastomas are different manifestations of transformed glial precursors, with each tumor expressing a unique combination of mutagenic events . In conclusion, the debate surrounding the origin of cerebral granular cell tumors is still not settled . The association of granular cell tumor with glioblastoma multiforme remains difficult to explain . The available evidence seems to suggest that cerebral granular cell tumors may arise from glial precursors, and, therefore, when a granular cell tumor occurs in the brain, the possibility of a coexisting malignant glioma should be considered . The authors would like to thank Dr . Dan W . Fults for editorial assistance and Keith E . Johnson for photographic assistance .
References 1 . Abrikossoff A . Uber Myome, ausgehend van der quergestreiften willkurlichen Muskulatur . Virchows Arch [A) 1926 ;260 :215-33 . 2 . Becker DH, Wilson CB . Symptomatic parasellar granular cell tumors . Neurosurgery 1981 ;8 :173-80 .
Harris et al
3 . Dickson DW, Suzuki KI, Kanner R, Weitz S, Horoupian DS . Cerebral granular cell tumor : immunohisrochemical and electron microscopic study. J Neuropathol Exp Neurol 1986 ;45 :304-14 . 4 . Fisher ER, Wechsler H . Granular cell myoblastoma : a misnomer : electron microscopic and histochemical evidence concerning its Schwann cell derivation and nature . Cancer 1962 ;15 :936-54 . 5 . Friede RL, Yasargil MG . Suprasellar neoplasm with agranular cell component . J Neuropathol Exp Neurol 1977 ;36 :769-82 . 6 . Fust JA, Custer RP . On the neurogenesis of so-called granular cell myoblastoma. Am J Clin Partial 1949 ;19:522-35 . 7 . Hori A, Altmannsberger M, Spoerri 0, Beuche W . Granular cell tumour in the third ventricle . Acta Neurochir (Wien) 1985 ;74 :49-52 . 8 . Khansur T, Balducci L, Tavassoli M . Granular cell tumor : clinical spectrum of the benign and malignant entity . Cancer 1987 ; 60 :220-2 . 9 . Kornfeld M . Granular cell glioblasmma : a malignant granular cell neoplasm of astrocytic origin . J Neuropathol Exp Neurol 1986;45 :447-62 . 10 . Lechevaher B, Mandard JC, Adam Y, Da Silva DC, Bazin C, Courtheoux P . Tumeur a cellules granuleuses d'un hemisphere cerebral : interet de la recherche de Ia proreine acidegliofibrillaire . Rev Neurol (Paris) 1982 ;138 :619-29 . 11 . Markesbery WR, Duffy PE, Cowen D . Granular cell rumors of the central nervous system . J Neuropathol Exp Neurol 1973 ; 32 :92-109 . 12 . Marx J . Many gene changes found in cancer. Science 1989 ; 246 :1386-8 . 13 . RaoTV, Puri R, ReddyGNN . Intracranial trigeminalnervegranular cell myoblasroma: case report . J Neurosurg 1983 ;59 :706-9 . 14 . Sakurama N, Matsukado Y, Marubayashi T, Kodama T . Granular cell tumor of the brain and its cellular identity . Acta Neurochir (Wien) 1981 ;56 :81-94 . 15 . Stefansson K, Wollmann RL. S-100 protein in granular cell tumors . Cancer 1982 ;49 :1834-8 . 16 . Traub P . Intermediate neurofilaments . Berlin: Springer, 1985 : 14-517 . Ule G, Tschahargane C, Haag D, Berlet H, Volk B . Maligner granular-zelltumor des Grofihirnmarkes . Acta Neuropathol (Berl) 1975 ;32 :143-55 .
