Child's Nerv Syst (1992) 8:268-272
RGNS 9 Springer-Verlag 1992
Meduilomyoblastoma: report of two cases David Schiffer ~, Maria Teresa Giordana 1, Stefano Pezzotta 2, Tiziana Pezzulo 1, and Maria Claudia Vigliani ~ Department of Neurology, University of Turin, Via Cherasco, 15, 1-10126 Turin, Italy z Department of Neurosurgery, University of Pavia, Pavia, Italy Received January 20, 1992
Abstract. Two cases of medullomyoblastoma in children
Case 2
are described. The muscular component showed different features in the two cases and were associated with neuronal differentiation. Morphological, immunohistochemical, and electron microscopical findings are presented. The origin of the muscular component is discussed in relation to the findings in other cases of the literature. Both differentiation from primitive neuroepithelial cells and derivation from ectomesenchyme are considered.
M.T., an 8-year-old girl. Three months before admission she started vomiting and suffered confusion. On admission, besides cerebellar symptoms, there were intracranial hypertension and hypertonia of all four limbs. CT showed triventricular hydrocephalus and a tumor mass in the inferior vermis with compression of the medulla oblongata. At operation a tumor mass involving the vermis was totally removed. The patient recovered quickly. She underwent radiotherapy and chemotherapy and is still alive.
Material and methods Key word: Medullomyoblastoma
A medulloblastoma containing muscle cells was first reported in 1933 by Marinesco and Goldstein [31], who called it "medullomyoblastoma". Since then just over 30 more cases have been reported. With the exception o f two cases, one in a 26-year-old [15] and the other in a 40-yearold [36], all have been in children. The main unresolved problem concerning this tumor is the origin of the muscular component. It might be the product of cell differentiation, but other interpretations of the available evidence are possible. Two cases are reported in the present paper.
Surgical specimens of the tumors were fixed in 10% formalin and processed for routine paraffin embedding. Seven-micron-thick sections were stained with hematoxylin-eosin, cresyl violet, the PAS reaction, Gomori's stain for reticulin, and Bodian staining. Immunohistochemical analysis using the peroxidase-antiperoxidase or Strept Avidin Biotin Complex peroxidase-labeled method was performed with the following antibodies: desmin (Dako, 1 : 350), neurofilaments (Sternberger, SMI 31, SMI 32 1:500), glial fibrillary acidic protein (GFAP) (antiserum Dako 1 : 400), e-sm actin (monoclonal antibody, Sigma, 1:200), and vimentin (monoclonal antibody, Dako, 1:20). Sections retrieved from paraffin blocks were embedded in hydrophilic resin LR White (London Resin) and processed for electron microscopy.
Results Case 1
Case reports Case 1 T.V., a 7-year-old boy. One year before admission he started to complain of headache and suffered vomiting. A few days before admission, ataxia, neck rigidity, and papilledema appeared. Ventriculography (1971) demonstrated triventricular hydrocephalus; the IV ventricle was not visualized. At operation, a tumor, soft and white-grayish in color, was seen in the inferior part of the roof of the IV ventricle. Apparently complete removal was carried out, but the child died a few days later. Correspondence to: D. Schiffer
The general appearance was that typical of medulloblastoma: high cell density, isomorphic cells, many mitoses (Fig. 1 a), formation of many Homer-Wright rosettes, small necrotic loci, and a vasculature formed mainly of small and middle size vessels, sometimes with slight endothelial hyperplasia. In some areas, many cells showed a vesiculous nucleus with a prominent nucleolus and a pear-shaped cytoplasm; with Bodian staining this cytoplasm was dark brown with short single processes. They had a clear neuronal appearance (Fig. I b). Large areas of the tumor were entirely formed out of elongated and eosinophilic cells with marked cross-striation (Fig. 1 c).
269
Fig. 1. a Classic appearance of medulloblastoma; hematoxylineosin (HE), x 110. b Area of neuronal differentiation; Bodian, x 290. e Cross-striation of muscle fibers; HE x 290. d Clearcut separation of areas with muscle fibers; HE, x 90
They showed a clear-cut border toward classic tumor parenchyma. Frequently, muscle cells showed a perivascular distribution and formed digitations in various directions (Fig. 1 d). No transition was found from muscle cells to classic tumor cells. In the areas with neuronal differentiation, stained by the Bodian method, many cells reacted intensely positively for neurofilament antibodies (Fig. 2d). The muscle cells reacted intensely positively for desmin and most cells positive for desmin showed the appearance of differentiated muscle cells (Fig. 2 a), often grouped around vessels (Fig. 2b). G F A P decorated some scattered cells with short and thick processes, identified as local reactive astrocytes, c~-sm-Actin decorated some pericapillary cells and some cells of the tunica media, but none of the muscle cells in the perivascular position. Electron microscopy showed clearly the striation of muscle cells with myofibrils and Z band material. Less differentiated and transition cells were not identified. Case 2
The histological appearance of the tumor in case 2 was more or less superimposable upon that of case 1. In this case, too, clear neuronal differentiation was present, with many cells showing a vesiculous nucleus with a prominent nucleolus and short apical processes with Bodian staining. The muscle component was formed by few elon-
gated cells with many irregular and small cells distributed over a wide area in the tumor, admixed with the classic tumor cells (Fig. 2 c). Cells with neuronal differentiation reacted positively for neurofilaments. Scattered GFAP-positive glia cells were local reactive astrocytes. Desmin showed a few elongated cells and many irregularly shaped and small round cells dispersed in the tumor parenchyma (Fig. 2 d - f ) . Electron microscopy showed cross-striation in some cells and the occurrence of myofibrillated material only in many others. Discussion The tumors in the two presented cases are without any doubt medulloblastomas with neuronal differentiation and a striated muscle component which showed different distributions and different degrees of differentiation in the tumors. The occurrence of myocytic cells in medulloblastoma is rather rare and their histogenesis controversial. The analysis of most published cases does not give any evidence of clinico-biologic peculiarities in relation to classic medulloblastomas, which could help in clarifying the origin of the muscle cells. Medullomyoblastomas are mainly localized in the vermis (22/25 cases), the mean patient age is 7.4 years and the median age 5 years. Only two cases have been reported in adults [15, 36]. There is a predominance of male patients, 19 : 5, giving a
270
Fig. 2. a Muscle fibers react positive for desmin; PAP-DAB, x 290. b Desmin-positive muscle fibers in a perivascular position; PAPDAB, x 180. e Muscle cells admixed with tumor cells; HE, x 180. d Area with cells positive to neurofilament antibodies; SMI 31, PAP-DAB, x 180. e Large and small cells positive for desmin, PAP-DAB; x 290. f The same as e, x 720
male: female ratio of 3.8 : 1. The m e a n time f r o m the onset of s y m p t o m s to o p e r a t i o n available for 16 cases, was 3.7 m o n t h s and the m e d i a n 3 m o n t h s . In three cases it was m o r e than 6 m o n t h s [6, 18, and this study]. Patients u n d e r w e n t surgery in 23 cases and 8 were also irradiated. Survivals are n o t easily c o m p a r a b l e ; generally, they were very short, only in four cases longer than 1 year. In our case 2 survival was m o r e than 2 years (the patient is still alive); the patient in case 1 died after surgery. The muscle c o m p o n e n t is generally striated; a s m o o t h muscle c o m p o n e n t has been f o u n d only twice [15, 43]. In
the case of H611 et al. [20] no cross-striation was evident at light microscopy, but 7-nm intermediate filaments, typical of myoblasts, were seen ultrastructurally, as in our case 2. A positive reaction for acfin, desmin, and myoglobin has been recently found in some cases [1, 17, 36, our two cases]. Concomitant glial and neuronal differentiation has been found in five cases [7, 20, 32, 37, 38], glial differentiation alone in one case [12], and neuronal differentiation alone in two cases (our two cases). In four cases the t u m o r also contained melanotic cells [3, 7, 14, 24]. This is not different from what is found in elastic medulloblastomas [8].
271 Different theories have been proposed of the histogenesis of the muscular c o m p o n e n t in medullomyoblastoma, and it cannot be ruled out that there m a y be more than one origin. The m o s t credited theory today is that undifferentiated neuroepithelial cells in medulloblastomas can undergo not only glial, neuronal, and photoreceptor differentiation [9, 10, 2 5 - 2 7 , 30, 34], but also myogenic differentiation. They are pluripotential and thus possess myogenic capabilities [12, 20, 36, 38]. There are confirmations of this theory: evidence of desmin expression in primitive neuroectodermic tumors without advanced myoblastic differentiation [17]; striated muscle differentiation shown in three p e r m a n e n t cell lines from h u m a n gliomas [22] and also in a cell line from a medulloblast o m a [16]. In the case published by H611 et al. [20] there was a transition from neoplastic cells with i m m u n o c y t o chemical evidence of a myogenic differentiation to large myocytes with cross-striation on electron microscopy. This theory could easily apply to our case 2, where myoblasts were scattered in the t u m o r with an evident transition from more immature to more differentiated cell forms. Other theories have been put forward, such as that regarding the t u m o r as a malignant t e r a t o m a or a malignant teratoid t u m o r [3, 6, 21, 32, 35]. This has received little support, because the nonectodermal c o m p o n e n t in m e d u l l o m y o b l a s t o m a is restricted to cross-striated muscle cells [39]. However, in a recent case [11] there were elements derived f r o m all three germ layers, which might speak in favor of the t e r a t o m a theory. Still another theory is that the myoblastic c o m p o n e n t derives f r o m multipotential endothelial cells [41]. One hypothesis which has not yet been confuted is that of a derivation f r o m mesenchymal cells situated in the t u m o r or in its vicinity [4, 18, 24, 28, 37, 40, 42], which are usually referred to as neuro- or ectomesenchyme. The pluripotentiality of these cells has been advocated to explain the occurrence of striated muscle cells in the leptomeninges, even though this occurrence has been extremely rare [33], mainly in trisomy 13 [2, 19, 23]. The possible origin of the muscle cells in these cases has been considered to be ectomesenchyme to which neural crest contributes [19, 33], although others suggest displaced mesodermal elements [2]. To the same origin could be referred cerebellar r h a b d o m y o s a r c o m a s , besides undifferentiated perivascular mesenchymal cells [29]. The origin from ectomesenchyme could be advocated in order to explain the perivascular situation of muscle cells in our case, since in some of the cases with muscle cells in the meninges it has been supposed that muscle cells accompanied meningeal penetrating vessels [2, 19, 23]. It is possible that in m e d u l l o m y o b l a s t o m a the muscular c o m p o n e n t in the t u m o r develops f r o m leptomeningeal muscle cells or their precursors, brought into the nervous p a r e n c h y m a by meningeal penetrating vessels. The clear-cut circumscription of the areas containing muscle cells and the differentiation of most of them in our case 2 might be confirmatory elements. There was in this case no intimate admixture, as was observed in our case 1 and in other cases in the literature [32, 36]. It remains to be elucitated how and whether these cells
transform, bearing in mind that not always do they have a malignant appearance [38] as in our case 1. This uncertainty parallels that regarding transforming genes involved in the pathogenesis of medulloblastomas [20]. The occurrence of melanin-containing cells in medull o m y o b l a s t o m a as well as in classic medulloblastoma [5, 13] is regarded as further support for the theory that the t u m o r originates f r o m the neuronal crest-derived ectomesenchyme.
References 1. Abenoza P, Wick M (1986) Primitive cerebral neuroectodermal tumor with rhabdomyoblastic differentiation. Ultrastruct Pathol 10:347-354 2. Ambler M (1977) Striated muscle cells in the leptomeninges in cerebral dysplasia. Acta Neuropathol 40:269-271 3. Banarjee A, Kalk V (1973) Teratoid tumor of the cerebellum. J Pathol 11:285-287 4. Boellaard J (1964) Ein Medulloblastom mit quergestreiften Muskelfasern. Arch Psychiatr Nervenkr 206:228-236 5. Boesel CP, Suhan JP, Sayers MP (1978) Melanotic medulloblastoma. Report of a case with ultrastructural findings. J Neuropathot Exp Neurol 37:531-543 6. Bofin P, Ebels E (1963) A case of medullomyoblastoma. Acta Neuropathol 2:309-311 7. Bonnin JM, Wilson ER, Garcia JH (1989) Medulloblastoma with neuronal, glial, striated muscle and pigment epithelium differentiation (abstract). Can J Neuropathol 16:227 8. Burger PC, Grahmann PC, Bliestle A, Kleihues P (1987) Differentiation in the medulloblastoma: a histological and immunohistochemical study. Acta Neuropathol 73:115-123 9. Camins MB, Cravioto H, Epstein F, RansohoffJ (1980) Medullobtastoma: an ultrastructural study. Evidence for astrocytic and neuronal differentiation. Neurosurgery 6:398-411 10. Caputy AJ, McCullough DC, Manz HJ, Patterson K, Hammock MK (1987) A review of the factors influencing the prognosis of medullobtastoma: the importance of celt differentiation. J Neurosurg 66:80-87 11. Chowdhury C, Subimal R, Mahapatra A, Bhatia R (1985) Medullomyoblastoma: a teratoma. Cancer 55:1495-1500 12. Dickson D, Hart M, Menezes A, Cancilla P (1983) Medulloblastoma with glial and rhabdomyoblastic differentiation. A myoglobin and glial fibrillary acidic protein immunohistochemical and ultrastructural study. J Neuropathol Exp Neurol 42:639-647 13. Dolman CL (1988) Melanotic medulloblastoma. A case report with immunohistochemical and ultrastructural examination. Acta Neuropathol 76:528-531 14. Duinkerke S, Sloof J, Gabreels F, Renier W, Thijsen H, Biesta J (1981) Melanotic rhabdomedullomyoblastoma or teratoid tumor of the cerebellar vermis. Clin Neurol Neurosurg 83:29-33 15. Galatioto S, Gaddoni G (1971) Miosarcomi primitivi del SNC. Acta Neurol (Napoli) 26:297-302 16. Giangaspero F, Pession A, Trer~ D, Badiali M, Galassi E, Ceccarelli C, Cavazzana A, Betts CM, Paolucci P, Stella M, Montaldi A (1991) Establishment of a human medulloblastoma cell line (BO-101) demonstrating skeletal muscle differentiation. Tumori 77:196-205 17. Gould V, Jansson D, Molenaar W, Rorke L, Trojanowski J, Lee V, Packer R, Franke W (1990) Primitive neuroectodermal tumours of the central nervous system. Patterns of expression of neuroendocrine markers, and all classes of intermediate filament protein. Lab Invest 62:498-509 18. GullottaF (1967)Das sogenannteMedulloblastom. (Monographie aus dem Gesamtgebiete der Neurologie und Psychiatrie, vol 118) Springer, Berlin Heidelberg New York
272 19. Hoffman S, Rorke L (1971) On finding striated muscle in the brain. J Neurol Neurosurg Psychiatry 34:761-764 20. H611T, Kleinhues P, Ya~argil MG, Wiestler OD (1991) Cerebellar medullomyoblastoma with advanced neuronal differentiation and hamartomatous component. Acta Neuropathol 82:408-413 21. Ingraham F, Bailey O (1946) Cystic teratomas and teratoid tumors of the central nervous system in infancy and childhood. J Neurosurg 3:511-532 22. Jacobsen PF, Jenkin DJ (1987) Four permanent cell lines established from human malignant gliomas, three exhibiting striated muscle differentiation. J Neuropathol Exp Neurol 46:431 450 23. Johnson ES, Ludwin SK (1984) Rhabdoneuroglial heterotopias of the pontine leptomeninges in trisomy 13. Arch Pathol Lab Med 108:906-908 24. Kalimo H, Paljarvi L, Ekfors T, Pelliniemi L (1987) Pigmented primitive neuroectodermal tumor with multipotential differentiation in cerebellum (pigmented medullomyoblastoma). A case with light- and electron-microscopic, and immunohistochemical analysis. Pediatr Neurosci 13:188-195 25. Katsetos CD, Herman MM, Frankfurter A, Collins VP, Walker CC, Barnard RO, Rubinstein L (1988) Dual neuronal and astroglial differentiation in cerebellar desmoplastic medulloblastoma: a further immunohistochemical characterization of the pale islands (abstract). J Neuropathol Exp Neurol 47:349 26. Kleihues P, Shibata T, Wiestler OD, Aguzzi A (1990) Morphological and immunohistochemical analysis of 330 medulloblastomas. Biwako Syrup Brain Tumor Pathol, Shiga 1990, p 25 27. KorfHW, Czerwionka M, Reiner J, Schachenmayr W, Schalken JJ, Grip W de, Gery I (1987) Immunocytochemical evidence of molecular photoreceptor markers in cerebellar medulloblastomas. Cancer 60:1763-1766 28. Lewis AJ (1973) Medulloblastoma with striated muscle fibers: case report. J Neurosurg 38:642-646 29. Lopes de Faria J (1957) Rhabdomyosarcoma of cerebellum. Arch Pathol 63:234-238 30. Mannoji H, Takeshita I, Fukui M, Ohta M, Kitamura K (1981) Glial fibrillary acidic protein in medulloblastoma. Acta Neuropathol 55:63-69
31. Marinesco G, Goldstein M (1933) Sur une forme anatomique, non encore d6crite, de m6dulloblastome: m6dullo-myo-blastome. Ann Anat Pathol 10:513-525 32. Misugi K, Liss L (1970) Medulloblastoma with cross-striated muscle: a fine structural study. Cancer 25:1279-1285 33. Nakamura Y, Nakashima T, Komatsu Y, Hashimoto T, Hachisuka H (1984) Striated muscle cells in the leptomeninges: an immunohistochemical study. Arch Pathol Lab Med 108:561-563 34. Newman R, Jasani B, Williams ED (/983) A simple post-embedding system for rapid demonstration of tissue antigens under the electron microscope. Histochem J 15:543-555 35. Packer RJ, Sutton RN, Rorke LB, Littman PA, Sposto R, Rosenstock JG, Bruce DA, Schut L (1984) Prognostic importance of cellular differentiation in medulloblastoma in childhood. J Neurosurg 61:296-301 36. Patt S, Oppel F, Cervos-Navarro J (1989) Zur Frage des Medullomyoblastoms. Zentralbl Allg Pathol Anat 135:445-455 37. Rao C, Friedlander M, Klein E, Anzil A, Sher J (1990) Medullomyoblastoma in adult. Cancer 65:157-163 38. Shuangshoti S, O'Charoen S (1983) Cerebellar neoplasm of mixed mesenchymal and neuroepithelial origin. Case report. J Neurosurg 59:337-343 39. Smith T, Davidson R (1984) Medullomyoblastoma. A histologic, immunohistochemical, and ultrastructural study. Cancer 54:323-332 40. Stahlberger R, Friede R (1977) Fine structure of myomedulloblastoma. Acta Neuropathol 37:43-48 41. Vuia O, Hager H (1975) Central neuroblastic tumour associated with smooth muscle fibers. Eur Neurol 13:258-272 42. Walter G, Brucher J (/979) Ultrastructural study of medullomyoblastoma. Acta Neuropathol 48:211-214 43. Warzok R, J~inisch W, Schreiber D (1982) Gliomedullomyoblastoma. A contribution to the morphology and biological behaviour of myogenic brain tumors. Zentralbl Allg Pathol Anat 126:5-15 44. Ziilch KJ (1941) Ein Medulloblastom mit glatten Mukelfasern. Arch Psychiatr Nervenkr 114:349-352
RGNS 9 Springer-Verlag 1992
Meduilomyoblastoma: report of two cases David Schiffer ~, Maria Teresa Giordana 1, Stefano Pezzotta 2, Tiziana Pezzulo 1, and Maria Claudia Vigliani ~ Department of Neurology, University of Turin, Via Cherasco, 15, 1-10126 Turin, Italy z Department of Neurosurgery, University of Pavia, Pavia, Italy Received January 20, 1992
Abstract. Two cases of medullomyoblastoma in children
Case 2
are described. The muscular component showed different features in the two cases and were associated with neuronal differentiation. Morphological, immunohistochemical, and electron microscopical findings are presented. The origin of the muscular component is discussed in relation to the findings in other cases of the literature. Both differentiation from primitive neuroepithelial cells and derivation from ectomesenchyme are considered.
M.T., an 8-year-old girl. Three months before admission she started vomiting and suffered confusion. On admission, besides cerebellar symptoms, there were intracranial hypertension and hypertonia of all four limbs. CT showed triventricular hydrocephalus and a tumor mass in the inferior vermis with compression of the medulla oblongata. At operation a tumor mass involving the vermis was totally removed. The patient recovered quickly. She underwent radiotherapy and chemotherapy and is still alive.
Material and methods Key word: Medullomyoblastoma
A medulloblastoma containing muscle cells was first reported in 1933 by Marinesco and Goldstein [31], who called it "medullomyoblastoma". Since then just over 30 more cases have been reported. With the exception o f two cases, one in a 26-year-old [15] and the other in a 40-yearold [36], all have been in children. The main unresolved problem concerning this tumor is the origin of the muscular component. It might be the product of cell differentiation, but other interpretations of the available evidence are possible. Two cases are reported in the present paper.
Surgical specimens of the tumors were fixed in 10% formalin and processed for routine paraffin embedding. Seven-micron-thick sections were stained with hematoxylin-eosin, cresyl violet, the PAS reaction, Gomori's stain for reticulin, and Bodian staining. Immunohistochemical analysis using the peroxidase-antiperoxidase or Strept Avidin Biotin Complex peroxidase-labeled method was performed with the following antibodies: desmin (Dako, 1 : 350), neurofilaments (Sternberger, SMI 31, SMI 32 1:500), glial fibrillary acidic protein (GFAP) (antiserum Dako 1 : 400), e-sm actin (monoclonal antibody, Sigma, 1:200), and vimentin (monoclonal antibody, Dako, 1:20). Sections retrieved from paraffin blocks were embedded in hydrophilic resin LR White (London Resin) and processed for electron microscopy.
Results Case 1
Case reports Case 1 T.V., a 7-year-old boy. One year before admission he started to complain of headache and suffered vomiting. A few days before admission, ataxia, neck rigidity, and papilledema appeared. Ventriculography (1971) demonstrated triventricular hydrocephalus; the IV ventricle was not visualized. At operation, a tumor, soft and white-grayish in color, was seen in the inferior part of the roof of the IV ventricle. Apparently complete removal was carried out, but the child died a few days later. Correspondence to: D. Schiffer
The general appearance was that typical of medulloblastoma: high cell density, isomorphic cells, many mitoses (Fig. 1 a), formation of many Homer-Wright rosettes, small necrotic loci, and a vasculature formed mainly of small and middle size vessels, sometimes with slight endothelial hyperplasia. In some areas, many cells showed a vesiculous nucleus with a prominent nucleolus and a pear-shaped cytoplasm; with Bodian staining this cytoplasm was dark brown with short single processes. They had a clear neuronal appearance (Fig. I b). Large areas of the tumor were entirely formed out of elongated and eosinophilic cells with marked cross-striation (Fig. 1 c).
269
Fig. 1. a Classic appearance of medulloblastoma; hematoxylineosin (HE), x 110. b Area of neuronal differentiation; Bodian, x 290. e Cross-striation of muscle fibers; HE x 290. d Clearcut separation of areas with muscle fibers; HE, x 90
They showed a clear-cut border toward classic tumor parenchyma. Frequently, muscle cells showed a perivascular distribution and formed digitations in various directions (Fig. 1 d). No transition was found from muscle cells to classic tumor cells. In the areas with neuronal differentiation, stained by the Bodian method, many cells reacted intensely positively for neurofilament antibodies (Fig. 2d). The muscle cells reacted intensely positively for desmin and most cells positive for desmin showed the appearance of differentiated muscle cells (Fig. 2 a), often grouped around vessels (Fig. 2b). G F A P decorated some scattered cells with short and thick processes, identified as local reactive astrocytes, c~-sm-Actin decorated some pericapillary cells and some cells of the tunica media, but none of the muscle cells in the perivascular position. Electron microscopy showed clearly the striation of muscle cells with myofibrils and Z band material. Less differentiated and transition cells were not identified. Case 2
The histological appearance of the tumor in case 2 was more or less superimposable upon that of case 1. In this case, too, clear neuronal differentiation was present, with many cells showing a vesiculous nucleus with a prominent nucleolus and short apical processes with Bodian staining. The muscle component was formed by few elon-
gated cells with many irregular and small cells distributed over a wide area in the tumor, admixed with the classic tumor cells (Fig. 2 c). Cells with neuronal differentiation reacted positively for neurofilaments. Scattered GFAP-positive glia cells were local reactive astrocytes. Desmin showed a few elongated cells and many irregularly shaped and small round cells dispersed in the tumor parenchyma (Fig. 2 d - f ) . Electron microscopy showed cross-striation in some cells and the occurrence of myofibrillated material only in many others. Discussion The tumors in the two presented cases are without any doubt medulloblastomas with neuronal differentiation and a striated muscle component which showed different distributions and different degrees of differentiation in the tumors. The occurrence of myocytic cells in medulloblastoma is rather rare and their histogenesis controversial. The analysis of most published cases does not give any evidence of clinico-biologic peculiarities in relation to classic medulloblastomas, which could help in clarifying the origin of the muscle cells. Medullomyoblastomas are mainly localized in the vermis (22/25 cases), the mean patient age is 7.4 years and the median age 5 years. Only two cases have been reported in adults [15, 36]. There is a predominance of male patients, 19 : 5, giving a
270
Fig. 2. a Muscle fibers react positive for desmin; PAP-DAB, x 290. b Desmin-positive muscle fibers in a perivascular position; PAPDAB, x 180. e Muscle cells admixed with tumor cells; HE, x 180. d Area with cells positive to neurofilament antibodies; SMI 31, PAP-DAB, x 180. e Large and small cells positive for desmin, PAP-DAB; x 290. f The same as e, x 720
male: female ratio of 3.8 : 1. The m e a n time f r o m the onset of s y m p t o m s to o p e r a t i o n available for 16 cases, was 3.7 m o n t h s and the m e d i a n 3 m o n t h s . In three cases it was m o r e than 6 m o n t h s [6, 18, and this study]. Patients u n d e r w e n t surgery in 23 cases and 8 were also irradiated. Survivals are n o t easily c o m p a r a b l e ; generally, they were very short, only in four cases longer than 1 year. In our case 2 survival was m o r e than 2 years (the patient is still alive); the patient in case 1 died after surgery. The muscle c o m p o n e n t is generally striated; a s m o o t h muscle c o m p o n e n t has been f o u n d only twice [15, 43]. In
the case of H611 et al. [20] no cross-striation was evident at light microscopy, but 7-nm intermediate filaments, typical of myoblasts, were seen ultrastructurally, as in our case 2. A positive reaction for acfin, desmin, and myoglobin has been recently found in some cases [1, 17, 36, our two cases]. Concomitant glial and neuronal differentiation has been found in five cases [7, 20, 32, 37, 38], glial differentiation alone in one case [12], and neuronal differentiation alone in two cases (our two cases). In four cases the t u m o r also contained melanotic cells [3, 7, 14, 24]. This is not different from what is found in elastic medulloblastomas [8].
271 Different theories have been proposed of the histogenesis of the muscular c o m p o n e n t in medullomyoblastoma, and it cannot be ruled out that there m a y be more than one origin. The m o s t credited theory today is that undifferentiated neuroepithelial cells in medulloblastomas can undergo not only glial, neuronal, and photoreceptor differentiation [9, 10, 2 5 - 2 7 , 30, 34], but also myogenic differentiation. They are pluripotential and thus possess myogenic capabilities [12, 20, 36, 38]. There are confirmations of this theory: evidence of desmin expression in primitive neuroectodermic tumors without advanced myoblastic differentiation [17]; striated muscle differentiation shown in three p e r m a n e n t cell lines from h u m a n gliomas [22] and also in a cell line from a medulloblast o m a [16]. In the case published by H611 et al. [20] there was a transition from neoplastic cells with i m m u n o c y t o chemical evidence of a myogenic differentiation to large myocytes with cross-striation on electron microscopy. This theory could easily apply to our case 2, where myoblasts were scattered in the t u m o r with an evident transition from more immature to more differentiated cell forms. Other theories have been put forward, such as that regarding the t u m o r as a malignant t e r a t o m a or a malignant teratoid t u m o r [3, 6, 21, 32, 35]. This has received little support, because the nonectodermal c o m p o n e n t in m e d u l l o m y o b l a s t o m a is restricted to cross-striated muscle cells [39]. However, in a recent case [11] there were elements derived f r o m all three germ layers, which might speak in favor of the t e r a t o m a theory. Still another theory is that the myoblastic c o m p o n e n t derives f r o m multipotential endothelial cells [41]. One hypothesis which has not yet been confuted is that of a derivation f r o m mesenchymal cells situated in the t u m o r or in its vicinity [4, 18, 24, 28, 37, 40, 42], which are usually referred to as neuro- or ectomesenchyme. The pluripotentiality of these cells has been advocated to explain the occurrence of striated muscle cells in the leptomeninges, even though this occurrence has been extremely rare [33], mainly in trisomy 13 [2, 19, 23]. The possible origin of the muscle cells in these cases has been considered to be ectomesenchyme to which neural crest contributes [19, 33], although others suggest displaced mesodermal elements [2]. To the same origin could be referred cerebellar r h a b d o m y o s a r c o m a s , besides undifferentiated perivascular mesenchymal cells [29]. The origin from ectomesenchyme could be advocated in order to explain the perivascular situation of muscle cells in our case, since in some of the cases with muscle cells in the meninges it has been supposed that muscle cells accompanied meningeal penetrating vessels [2, 19, 23]. It is possible that in m e d u l l o m y o b l a s t o m a the muscular c o m p o n e n t in the t u m o r develops f r o m leptomeningeal muscle cells or their precursors, brought into the nervous p a r e n c h y m a by meningeal penetrating vessels. The clear-cut circumscription of the areas containing muscle cells and the differentiation of most of them in our case 2 might be confirmatory elements. There was in this case no intimate admixture, as was observed in our case 1 and in other cases in the literature [32, 36]. It remains to be elucitated how and whether these cells
transform, bearing in mind that not always do they have a malignant appearance [38] as in our case 1. This uncertainty parallels that regarding transforming genes involved in the pathogenesis of medulloblastomas [20]. The occurrence of melanin-containing cells in medull o m y o b l a s t o m a as well as in classic medulloblastoma [5, 13] is regarded as further support for the theory that the t u m o r originates f r o m the neuronal crest-derived ectomesenchyme.
References 1. Abenoza P, Wick M (1986) Primitive cerebral neuroectodermal tumor with rhabdomyoblastic differentiation. Ultrastruct Pathol 10:347-354 2. Ambler M (1977) Striated muscle cells in the leptomeninges in cerebral dysplasia. Acta Neuropathol 40:269-271 3. Banarjee A, Kalk V (1973) Teratoid tumor of the cerebellum. J Pathol 11:285-287 4. Boellaard J (1964) Ein Medulloblastom mit quergestreiften Muskelfasern. Arch Psychiatr Nervenkr 206:228-236 5. Boesel CP, Suhan JP, Sayers MP (1978) Melanotic medulloblastoma. Report of a case with ultrastructural findings. J Neuropathot Exp Neurol 37:531-543 6. Bofin P, Ebels E (1963) A case of medullomyoblastoma. Acta Neuropathol 2:309-311 7. Bonnin JM, Wilson ER, Garcia JH (1989) Medulloblastoma with neuronal, glial, striated muscle and pigment epithelium differentiation (abstract). Can J Neuropathol 16:227 8. Burger PC, Grahmann PC, Bliestle A, Kleihues P (1987) Differentiation in the medulloblastoma: a histological and immunohistochemical study. Acta Neuropathol 73:115-123 9. Camins MB, Cravioto H, Epstein F, RansohoffJ (1980) Medullobtastoma: an ultrastructural study. Evidence for astrocytic and neuronal differentiation. Neurosurgery 6:398-411 10. Caputy AJ, McCullough DC, Manz HJ, Patterson K, Hammock MK (1987) A review of the factors influencing the prognosis of medullobtastoma: the importance of celt differentiation. J Neurosurg 66:80-87 11. Chowdhury C, Subimal R, Mahapatra A, Bhatia R (1985) Medullomyoblastoma: a teratoma. Cancer 55:1495-1500 12. Dickson D, Hart M, Menezes A, Cancilla P (1983) Medulloblastoma with glial and rhabdomyoblastic differentiation. A myoglobin and glial fibrillary acidic protein immunohistochemical and ultrastructural study. J Neuropathol Exp Neurol 42:639-647 13. Dolman CL (1988) Melanotic medulloblastoma. A case report with immunohistochemical and ultrastructural examination. Acta Neuropathol 76:528-531 14. Duinkerke S, Sloof J, Gabreels F, Renier W, Thijsen H, Biesta J (1981) Melanotic rhabdomedullomyoblastoma or teratoid tumor of the cerebellar vermis. Clin Neurol Neurosurg 83:29-33 15. Galatioto S, Gaddoni G (1971) Miosarcomi primitivi del SNC. Acta Neurol (Napoli) 26:297-302 16. Giangaspero F, Pession A, Trer~ D, Badiali M, Galassi E, Ceccarelli C, Cavazzana A, Betts CM, Paolucci P, Stella M, Montaldi A (1991) Establishment of a human medulloblastoma cell line (BO-101) demonstrating skeletal muscle differentiation. Tumori 77:196-205 17. Gould V, Jansson D, Molenaar W, Rorke L, Trojanowski J, Lee V, Packer R, Franke W (1990) Primitive neuroectodermal tumours of the central nervous system. Patterns of expression of neuroendocrine markers, and all classes of intermediate filament protein. Lab Invest 62:498-509 18. GullottaF (1967)Das sogenannteMedulloblastom. (Monographie aus dem Gesamtgebiete der Neurologie und Psychiatrie, vol 118) Springer, Berlin Heidelberg New York
272 19. Hoffman S, Rorke L (1971) On finding striated muscle in the brain. J Neurol Neurosurg Psychiatry 34:761-764 20. H611T, Kleinhues P, Ya~argil MG, Wiestler OD (1991) Cerebellar medullomyoblastoma with advanced neuronal differentiation and hamartomatous component. Acta Neuropathol 82:408-413 21. Ingraham F, Bailey O (1946) Cystic teratomas and teratoid tumors of the central nervous system in infancy and childhood. J Neurosurg 3:511-532 22. Jacobsen PF, Jenkin DJ (1987) Four permanent cell lines established from human malignant gliomas, three exhibiting striated muscle differentiation. J Neuropathol Exp Neurol 46:431 450 23. Johnson ES, Ludwin SK (1984) Rhabdoneuroglial heterotopias of the pontine leptomeninges in trisomy 13. Arch Pathol Lab Med 108:906-908 24. Kalimo H, Paljarvi L, Ekfors T, Pelliniemi L (1987) Pigmented primitive neuroectodermal tumor with multipotential differentiation in cerebellum (pigmented medullomyoblastoma). A case with light- and electron-microscopic, and immunohistochemical analysis. Pediatr Neurosci 13:188-195 25. Katsetos CD, Herman MM, Frankfurter A, Collins VP, Walker CC, Barnard RO, Rubinstein L (1988) Dual neuronal and astroglial differentiation in cerebellar desmoplastic medulloblastoma: a further immunohistochemical characterization of the pale islands (abstract). J Neuropathol Exp Neurol 47:349 26. Kleihues P, Shibata T, Wiestler OD, Aguzzi A (1990) Morphological and immunohistochemical analysis of 330 medulloblastomas. Biwako Syrup Brain Tumor Pathol, Shiga 1990, p 25 27. KorfHW, Czerwionka M, Reiner J, Schachenmayr W, Schalken JJ, Grip W de, Gery I (1987) Immunocytochemical evidence of molecular photoreceptor markers in cerebellar medulloblastomas. Cancer 60:1763-1766 28. Lewis AJ (1973) Medulloblastoma with striated muscle fibers: case report. J Neurosurg 38:642-646 29. Lopes de Faria J (1957) Rhabdomyosarcoma of cerebellum. Arch Pathol 63:234-238 30. Mannoji H, Takeshita I, Fukui M, Ohta M, Kitamura K (1981) Glial fibrillary acidic protein in medulloblastoma. Acta Neuropathol 55:63-69
31. Marinesco G, Goldstein M (1933) Sur une forme anatomique, non encore d6crite, de m6dulloblastome: m6dullo-myo-blastome. Ann Anat Pathol 10:513-525 32. Misugi K, Liss L (1970) Medulloblastoma with cross-striated muscle: a fine structural study. Cancer 25:1279-1285 33. Nakamura Y, Nakashima T, Komatsu Y, Hashimoto T, Hachisuka H (1984) Striated muscle cells in the leptomeninges: an immunohistochemical study. Arch Pathol Lab Med 108:561-563 34. Newman R, Jasani B, Williams ED (/983) A simple post-embedding system for rapid demonstration of tissue antigens under the electron microscope. Histochem J 15:543-555 35. Packer RJ, Sutton RN, Rorke LB, Littman PA, Sposto R, Rosenstock JG, Bruce DA, Schut L (1984) Prognostic importance of cellular differentiation in medulloblastoma in childhood. J Neurosurg 61:296-301 36. Patt S, Oppel F, Cervos-Navarro J (1989) Zur Frage des Medullomyoblastoms. Zentralbl Allg Pathol Anat 135:445-455 37. Rao C, Friedlander M, Klein E, Anzil A, Sher J (1990) Medullomyoblastoma in adult. Cancer 65:157-163 38. Shuangshoti S, O'Charoen S (1983) Cerebellar neoplasm of mixed mesenchymal and neuroepithelial origin. Case report. J Neurosurg 59:337-343 39. Smith T, Davidson R (1984) Medullomyoblastoma. A histologic, immunohistochemical, and ultrastructural study. Cancer 54:323-332 40. Stahlberger R, Friede R (1977) Fine structure of myomedulloblastoma. Acta Neuropathol 37:43-48 41. Vuia O, Hager H (1975) Central neuroblastic tumour associated with smooth muscle fibers. Eur Neurol 13:258-272 42. Walter G, Brucher J (/979) Ultrastructural study of medullomyoblastoma. Acta Neuropathol 48:211-214 43. Warzok R, J~inisch W, Schreiber D (1982) Gliomedullomyoblastoma. A contribution to the morphology and biological behaviour of myogenic brain tumors. Zentralbl Allg Pathol Anat 126:5-15 44. Ziilch KJ (1941) Ein Medulloblastom mit glatten Mukelfasern. Arch Psychiatr Nervenkr 114:349-352
