Brain Pathology 1: 79-87 (1991)
REVIEW Mesenchymal, Non-Meningothelial Tumors of the Central Nervous System
Kurt Jellinger 1 and Werner Paulus 2
of Clinical Neurobiology, Lainz-Hospital, A-1 130 Vienna, Austria 2 Department of Pathology, University of Wurzburg, School of Medicine, D-8700 Wurzburg, Federal Republic of Germany 1 Ludwig Boltzmann Institute
The spectrum of non-meningothelial rnesenchymal tumors that may arise within the central nervous system is presented, based on the current classification of soft tissue tumors. Among malignant types, hemangiopericytoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma are the most frequent ones. Rare tumor entities are mentioned. As in soft tissue sarcomas, diagnosis is mainly based on light and electron microscopy, while immunohistochemistry can improve accuracy of diagnosis. Introduction
In the World Health Organization (WHO) classification of CNS tumors (l),mesenchymal, non-meningothelial tumors were listed among various headings: I. Tumors of meningeal and related tissues, including A. Meningeal sarcomas, 1. fibrosarcoma, 2. polymorphic cell sarcoma, 3. primary meningeal sarcomatosis; 11. Xanthomatous tumors (fibroxanthoma and xanthosarcoma); 111. Others (fibroma, chondroma, mesenchymal chondrosarcoma); IV. Other malformative tumors and tumor-like lesions (lipoma). The new version of the WHO Classification, separating benign and malignant tumors, will be partly based on modifications proposed by Scheithauer (2) which, in part, refer to the histologic classification of soft tissue tumors by Enzinger and Weiss (3). The occurrence of most of these tumor types in the CNS and its coverDedicated to the memory of our late friend Lucien Rubinstein Corresponding author: Dr. K. Jellinger, Ludwig Boltzmann Institute of Clinical Neurobiology, Lainz-Hospital. Wolkersbergenstrasse 1, A-1 130 Wien. Austria Tel. +43 (222) 801 10, ext. 3431; Fax +43 (222) 804 5401
ings is well documented (Table 1). Diagnosis is mainly based on light microscopy and may be supported by electron microscopy (4). Immunohistochemistry is often of limited value, except for tumors of muscle tissue or vascular origin (2-6; Table 2). Before diagnosing primary CNS sarcoma, both gliosarcoma and metastatic sarcoma have to be excluded. Tumors of Fibrous nssue and Fibrohistiocytic Tumors
1 . l . Fibroma Benign intracerebral tumors composed of fibrocytes or fibroblasts with variable amounts of collagen and blood vessels often showing degenerative changes (mucoid, calcification) are rare; about 15 cases have been reported, most in the first decades of life. They may be attached to the dura or are situated in deeper brain areas without relation to the dura (7). They are to be distinguished from fibrous meningioma, gliofibroma, and intracerebral schwannoma. Intracranial variants include single instances of angiofibroma (8), and myofibroblastoma (9). 1.2. Fibrous histiocytoma (fibroxanthoma) This benign tumor occurring in the skin is composed of a mixture of fibroblastic and histiocyte-like cells arranged in a storiform pattern, and accompanied by varying numbers of inflammatory and/or giant cells. Its primary occurrence in the CNS is debatable, since positive reaction with GFAP in most tumors of this type may suggest a glial neoplasm referred to as pleomorphic xanthoastrocytoma (PXA)(10), while some authors consider it a mesenchymal tumor identical with extracranial fibrous histiocytoma (FH), partly with astrocytic invasion (11). Only four well-documented totally GFAP-negative FH have been reported within the CNS (12,12a). 1.3. Fibrosarcoma (FS) Malignant mesenchymal neoplasms composed of fibroblasts with fascicular arrangement that show no other evidence of cellular differentiation are rarely observed in the CNS. In earlier studies, this tumor has been overdiagnosed and a number of cases have
1
K. Jellinger and W. Paulus Mesenchymal, non-meningothelialtumors
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Table 1 Mesenchymal, non-meningothelial tumors of the CNS MALIGNANT
BENIGN Fibrohisfiocytic tumors and tumors of fibrous tissue
Fibrosarcoma Malignant fibrous histiocytoma storiform-pleomorphic myxoid giant cell type (?) inflammatory
Fibroma Variants: Angiofibroma * Myofibroblastoma Fibrous histiocytoma (Fibroxanthoma)
Tumors of adipose tissue Liposarcoma
Lipoma Variant: Angiolipoma Tumors of muscle tissue
Leimyosarcoma R habdomyosarcoma embryonal botryoid (?) alveolar pleomorphic (?)
Leiomyoma (?I Variant: Glomangiomyoma
Tumors of blood vessels Angiosarcoma Kaposi's sarcoma (?) Hemangiopericytoma
Epithelioid hemangioendothelioma
Tumors of cartilage and bone-forming tissue Chondrosarcoma myxoid differentiated mesenchymal Osteosarcoma
Chondroma / Osteochondroma Osteoma / Osteoblastoma
Tumors of pluripotential mesenchyme Malignant mesenchymoma (?) Ectomesenchymoma * Tumors of uncertain or disputed origin Ewing's sarcoma Rhabdoid tumor
Myxoma Hernangioblastoma
Meningeal sarcomatosis Unclassified Sarcoma ONS
only single cases reported /
(?I occurrence in the CNS uncertain
been reclassified as malignant fibrous histiocytoma (MFH)(3). Transitions between FS and MFH may occur (3,4). FS is ultrastructurally composed only of fibroblasts and reacts with no specific marker except for vimentin (4). FS may arise from the dura, the lep-
tomeninges and, rarely, within the brain (13) and choroid plexus (14). It may occur spontaneously, in neurofibromatosis, and is not uncommon following cranial radiation often with long latencies (14).
K. Jellinger and W. Paulus: Mesenchymal. non-rneningothelial tumors
1.4. Malignant fibrous histiocytoma (MFH)
This commonest type of soft tissue sarcoma in adults arising preferentially in the retroperitoneum and in deep soft tissues is composed of a mixture of round and spindle cells, giant cells and optional xanthomatous cells. Five subtypes are separated (3): a) storiform-pleomorphic (most frequent); b) myxoid (myxofibrosarcoma);c) giant cell type; d) inflammatory, e) angiomatoid. About 20 cases of primary intracranial MFH have been described (15) including 6 personal ones from a series of 19 primary CNS sarcomas (13). They often arise within the meninges or are connected with them, while some are intracerebra1 without any relationship to the coverings. The age range is 13 to 76 years. MFH may occur following irradiation or after glioma exstirpation (16). The ultrastructural hallmark is heterogeneity of cell types including fibroblast-like, histiocyte-like, myofibroblast-like, undifferentiated cells and intermediate forms of these, some being predominantly fibroblastic (4,17). The histogenesis of MFH is under discussion, since some of the "histiocytic markers", e.g. alpha-1-antitrypsin, turned out to be rather nonspecific, and more specific mono-histiocytic markers are negative or inconsistently expressed by tumor cells (4,13,18).They are positive for vimentin, negative for desmin and S-100 protein and show a heterogeneous pattern of intermediate filament proteins with occasional expression of cytokeratin (4,19). There may be large intratumoral bulks of GFAP positive cells and processes (Fig. 1) that make separation of MFH from pleomorphic xanthoastrocytoma or gliosarcoma difficult (20,21). Differential diagnosis includes many pleomorphic neoplasms, e.g. liposarcoma, osteo- and chondrosarcoma, leio- and rhabdomyosarcoma, fibrosarcoma, carcinoma, malignant meningioma, and schwannoma. The prognosis of intracranial MFH is poor, with rapid local recurrence, distant metastases and survival not exceeding 10 months (13-17). Tumors of Adipose Tissue
2.1. Lipoma Rare localized masses of lipid tissue represent less than 0.5% of intracranial and 0.4% of spinal axis tumors. They occur at any age and are frequently found in the midline, over the corpus callosum (about SO%), the quadrigeminal plate, hypothalamus, in the cerebellopontine angle, and spinal cord. While most of the spinal lipomas invade the intradural space, a rare subtype termed angiolipoma (angiomyolipoma) is restricted to the epidural space (Fig. 2), but intracranial forms have also been reported. This tumor contains both vascular (angioid) and mature adipose elements (22). 2.2. Liposarcoma Liposarcoma, next to FMH the most common soft tissue sarcoma in adults, includes: a) well differentiated,
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b) myxoid (most common), c) round cell, and d) pleomorphic forms. Development from pre-existing lipoma is extremely rare. Immunohistochemistry may help in differential diagnosis, since adipocytes and lipoblasts are often S-100 protein positive. Only one intracranial case in the meninges has been reported (23). Tumors of Muscle Tissue
3. I . Benign forms Benign tumors of smooth muscle (leiomyoma) and of striated muscle (rhabdomyoma) are extremely rare in the CNS (24), while leptomeningeal rhabdomyomatosis (heterotopic skeletal muscle in the leptomeninges of the posterior fossa) is not infrequent (25). Single cases of sellar angiomyoma or glomangioma with organoid structure of tumor cells reacting with actin/myoglobin were observed (26). 3.2. Leiomyosarcoma (LMS) Primary intracranial LMS is exceedingly rare (13,14). It is located in the meninges of sellar or suprasellar region (27) or in the dura (28). Histologically, LMS is composed of short fascicles of elongated cells often showing prominent perinuclear vacuoles with nuclear indentation (Fig. 3): Immunostaining reveals positivity for vimentin, muscle-specific actin, while desmin may be negative (4,s). For differential diagnosis that includes all tumors composed of fascicles of spindle cells, electron microscopy is useful (4). 3.3. Rhabdomyosarcoma (RMS) This most common soft tissue sarcoma of childhood, arising predominantly in the head and neck region, only rarely occurs as primary CNS neoplasm. About 35 cases have been reported occurring in all ages and in various CNS locations, most commonly in posterior fossa in children and in cerebral hemispheres of adults (13,29). There are four types: a) embryonal RMS resembling developing muscle with densely packed small round cells, b) botryoid type of embryonal RMS with polypoid growth and abundant mucoid-myxomatous stroma, c) alveolar RMS with aggregates of poorly differentiated cells showing formation of honey-comb like spaces, and d) pleomorphic type that is difficult to distinguish from other pleomorphic sarcomas. Most intracranial RMS contain rhabdomyoblasts with eosinophilic cytoplasm and areas of poorly differentiated cells, only part of which show cross-striation. Immunohistochemistry reveals frequent expression of vimentin, desmin (90%), and myoglobin (66%), but only in a small percentage of undifferentiated cells (30). Ultrastructural demonstration of myofilaments may be of diagnostic value in cases being negative for myoglobin (4). Differential diagnosis includes Ewing's sarcoma, MFH, teratoma, medullomyoblastoma. Meningeal
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RMS is to be separated from meningeal extension of parameningeal head and neck tumors. Tumors of Blood Vessels
While the classification of soft tissue tumors and the old WHO classification of CNS tumors include (hem) angiomas as benign vascular neoplasms, they represent vascular malformations and, therefore, have to be excluded. 4.1. Hemangioendothelioma
This tumor considered of intermediate malignancy between hemangioma and angiosarcoma, has been rarely observed as primary CNS epithelioid hemangioendothelioma (3,31). Usually present in deep soft tissues and parenchymal organs, it is composed of strands or solid nests of rounded to spindled endothelial cells with intracellular miniature lumina and myxoid or hyaline stroma. Tumor cells are positive for factor VIII-related antigen (F-VIII-RA) and show ultrastructural evidence of Weibel-Palade bodies. 4.2. Angiosarcoma
Single instances of angiosarcoma have been observed in the spinal cord meninges after chordotomy (32) and within the brain (33). Tumor cells are inconsistently immunolabeled by F-VIII-RA and the lectin UEA-I (4), but more sensitively by RMS-120, a monoclonal antibody specific for endothelial cells (34). Neoplastic angioendotheliosis is now recognized as an intravasal (angiotropic) malignant large cell lymphoma mostly of B-cell type (35,36). 4.3. Kaposi's sarcoma The existence of primary CNS involvement by Ka-
posi's sarcoma is questionable. In all African cases without AIDS and in a few AIDS cases reported so far, spread of tumor into the CNS was accompanied by involvement of the lungs or other organs suggesting a metastatic process (37). 4.4. Hemangiopericytoma (HPC) This tumor occurs in both soft tissues, head and neck including orbit and sinonasal areas, and in intracranial and intraspinal spaces, where it has been regarded as a subtype of "angioblastic meningioma" (14). It accounts for 1 to 7% of meningeal neoplasms. Its histologic pattern of high cellularity with compact arrangement of plump, polygonal cells with illdefined cytoplasm in solid masses or sheets and around slit-like or "staghorn" vasculature lined by single endothelial cells, a variable reticulin network, and frequent mitoses is identical to HPC at other sites. EM appearance of CNS and soft tissue HPC is also largely identical and lacks interdigitating processes and well-developed desmosomes typical of meningiomas (2-4, 38-40). They further lack tight whorls, psammoma bodies and EMA (epithelial membrane antigen) immunoreactivity that are common features of meningiomas, but show abundant extracellular basal-lamina like material considered a diagnostic EM feature of HPC (38). Tumor cells are positive for vimentin and occasionally for desmin, muscle actin, alpha-actinin, laminin and type IV collagen (2, 38-41). The tumors are attached to the meninges and show compressive or invasive growth, but their topographic distribution, at least in some series, differs from common meningiomas, with more frequent involvement of the tentorium and infratentorial space (40,42), while others saw no topical differences (2,14). Meningeal HPC show aggres-
Table 2 lmmunohistochemistry of mesenchymal, non-meningothelial tumors of the CNS (2-6)
Tumor type Fibrous histiocytoma Mal.fibr.histiocytoma Fibrosarcoma Liposarcoma Leiomyosarcoma R habdomyosarcoma Angiosarcoma Hemangiopericytoma Chondrosarcoma Ewing's sarcoma Meningioma
Kmentin
Desmin
+ +
GFAP
Cker
NF
€MA
+
+
+
S700
FBRA
Mact
+
t
+
+
(+)
t
+ + t
(+)
t
GFAP glial fibrillary acidic protein; Cker cytokeratin; NF neurofilament protein; € M A epithelial membrane antigen; FBRA factor VIII-related antigen; Mact muscle actin + usually positive; (+) positive in some cases; t focal positivity in occasional cases
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1
2
3
4
5
6
7
8 Figure 1 Islands of pleomorphic astrocytes within a leptomeningeal malignant fibrous histiocytoma. Female, 55 yrs. GFAP; 2 Epidural angiolipoma at Th 5-7 causing progressive paraplegia. Female, 70 yrs, H&E; 3 Meningeal myxoid leiomyosarcoma. Note perinuclear vacuoles. Male, 4 yrs. muscle actin; 4 Mesenchymal chondrosarcoma of the tentorium. Male, 17 yrs, H&E; 5 Malignant ectornesenchymoma. A number of rhabdomyoblasts react with desmin. Female, 18 yrs; 6 Malignant ectomesenchymoma (same case) with scattered neoplastic ganglion cells. Neurofllament protein; 7 Epidural parietal Ewing's sarcoma infiltrating the dura mater. Female, 19 yrs, PAS; 8 Primary meningeal sarcomatosis with focal infiltration of the cerebral cortex. Female, 29 yrs, Vimentin.
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K. Jellinger and W. Paulus: Mesenchymal, non-meningothelialtumors
sive behavior, with recurrence rates between 20 and 80% and metastatic rates between 10 and 55%, and median survival between 58 and 84 months (2,43). Although some authors stress their classification as meningiomas (14), central HPC appears to represent a distinct entity probably originating from polyvalent mesenchymal cells and not from arachnoidal cap cells. Tumors of Cartilage and Bone-Forming Tissue
5.1. Chondroma and osteochondroma While the majority of benign cartilage tumors arise from the base of the skull, primary chondromas in the brain and meninges represent rare forms of extraosseous cartilagineous tumors. They may be attached to the dura over the cerebral convexities (44) or occur in the leptomeninges or choroid plexus (45). Some meningeal lesions contain bone mixed with cartilage (osteochondroma). They are to be separated from mixed tumors (teratoma, glioma) with cartilagineous areas. 5.2. Osteoma and osteoblastoma Extraosseous tumor-like lesions of differentiated bone-forming tissues in the CNS are exceedingly rare and the majority of these lesions are reactive bone formations or mixed mesenchymal tumors with bone and cartilage such as intracerebral osteochondrofibroma or osteolipoma, although cerebral or meningeal osteomas and osteochondrornas have been described (45).
5.3. Chondrosarcoma (CS) These rather frequent malignant cartilage tumors usually arising in bone and soft tissue may also occur in the craniospinal space. About 60 cases have been reported (14,46), including two personal cases (13). Three histologic subtypes are separated: a) Myxoid chondrosarcoma (chordoid sarcoma), a lobulated mass composed of.small chondroblasts and a myxoid matrix often resembling chondroid chordoma (47). Only single circumscribed or diffuse intracerebral and meningeal instances have been reported (14,47). b) Differentiated chondrosarcoma is extremely rare
at extraosseous locations and shows predominance of cartilaginous elements with few myxoid components. It occurs in the parasellar region, cerebellopontine angle or falx and is believed to arise from cartilaginous synchondroses or ectopic cartilage within brain and meninges (48). Distinction from chondroid chordoma considered by some as "low grade CS" (47) can be made by negative reaction with cytokeratins and EMA (chordoma) and S-100 protein
(cartilaginous areas) (49). Differentiated CS may develop extracranial metastases.
c) Mesenchymal chondrosarcoma is a malignant tumor composed of sheets of undifferentiated cells and interspersed islands of atypical chondroid or differentiated hyaline cartilage. The compact cell aggregates are composed of fusiform cells showing occasional palisading, separated by numerous thin-walled vascular spaces (Fig. 4). The small cells fail to express S-100 protein, but may stain for Leu-7 antigen and some for NSE (neuron specific enolase) (50). Craniospinal meninges are the most frequently reported extraskeletal sites, representing more than half of all cranial/intracranial CS (46,SO). Tumors without cartilagineous differentiation may be mistaken for HPC or may mimick neuroepitheial neoplasms, as tumor cells may form Homer-Wright-like rosettes. Immunohistochemistry is not overly helpful in the differential diagnosis to other small round cell neoplasms (50). Prognosis is poorer than in non-mesenchymal CS. The tumor tends to recur and has a high propensity to develop extracranial metastases. 5.4. Osteosarcoma (0s) Histology ranges from fibrosarcoma- or MFH-like (fibroblastic 0 s ) to extremely cellular neoplasms having irregular or spindle cell pattern (osteoblastic OS), while atypical cartilage (chondroblastic 0s) or giant cells (osteoclastic/giant cell 0 s ) may rarely become a predominant feature. 0 s arising primarily from the meninges is exceptional (Sl), and should be separated from that originating from the skull. Radiationinduced 0 s of pituitary fossa was observed (52). Other rare sarcomas with osseous components were reported in cerebellar vermis or fourth ventricle (see 45). Tumors of Pluripotential Mesenchyme
6.1. Malignant mesenchymoma and ectomesenchymoma This is a small and heterogenous group of sarcomas that exhibit two or more distinct and differentiated mesenchymal components besides the fibrous element (333). Whether tumors fulfilling these criteria do arise primarily in the CNS is unknown. We observed a primary CNS malignant ectomesenchymoma consisting of a mixture of embryonal RMS with neoplastic ganglion cells (Fig. 5,6). Tumors of Uncertain or Disputed Origin
7.1. Myxomn This benign tumor, histologically similar to Wharton's jelly of the umbilical cord, appears to be extremely rare in the CNS, but several types of meningeal tumors may mimick its appearance (54).
K. Jellinger and W. Paulus: Mesenchymal, non-meningothelial tumors
7.2.Hemangioblastoma Cerebellar hemangioblastomas are composed of endothelial cells, pericytes, and stromal cells. The supratentorial form was considered a subtype of angioblastic meningioma (14). Stromal cells are antigenetically polymorphous: they may express cytokeratin, GFAP, vimentin, Leu M1, Leu-7, actin, erythropoietin, S-100 protein and NSE (55). The pattern of antigen expression of the stromal cells does not allow identification of a definite histogenesis, but positivity of synaptophysin and a broad spectrum of neuropeptides suggests a neuroendocrine component of this tumor (56,57). 7.3.Ew-ng’s sarcoma Extraskeletal tumors histologically indistinguishable from Ewing’s sarcoma of bone have been documented as epidural masses in the cranial cavity and spinal canal predominantly in adolescents and young adults (58). The tumor is composed of densely packed, uniform, round or ovoid, lymphocyte-like cells with scanty cytoplasm often containing glycogen (Fig. 7). Prominent features include lobular pattern, lack of reticulin fibers, and rich vascularization. Usually vimentin is the only intermediate filament protein, but clusters of cells positive for cytokeratin and neurofilament proteins have been found (59), indicating that they are derived from a primitive pluripotent cell that may differentiate along different pathways. Epidural tumor masses in the spinal canal may show extensions to paraspinal musculature or distant metastases. 7.4. Rhabdoid tumor
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Sarcoma, Type not Otherwise Specified
Some tumors without recognizable light microscopic and ultrastructural differentiation and with no other specific immunohistochemical marker, apart from vimentin, are regarded as undifferentiated sarcomas provided that other tumor types are excluded. References 1.
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Rare extrarenal rhabdoid tumors may primarily arise within the CNS (60). They are composed of cellular sheets of undifferentiated monomorphic cells characterized by globular perinuclear inclusions that contain whorls of intermediate filaments. They stain for vimentin, but occasionally also for cytokeratin, desmin, EMA, NSE, and S-100 protein (61).
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Sarcomas arising from and diffusely infiltrating the meninges without forming large circumscribed tumor masses are rare and mainly occur in infants, children and rarely in adults (62). They may arise multifocally or show diffuse cerebrospinal spread with encasement of the spinal cord, and frequently invade the brain. Small lymphocyte-like, round or fusiforrn cells with dark nuclei and scanty cytoplasm represent the most common histologic appearance. Vimentin is usually the only intermediate filament (Fig. 8). Rhabdomyomatous and chondromatous sarcomatoses have been described. Diagnosis of meningeal sarcomatosis is only possible by exclusion of metastases of extraneural sarcoma, lymphoma, medulloblastoma, and other small cell neoplasms.
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30 40. Jellinger K. Paulus W, Slowik F (1990) The enigma of meningeal hemangiopericytoma. Brain Tumor Pathol 8 (in press) 41.Winek RR, Scheithauer BW, Wick WR (1989) Meningiomas, meningeal hemangiopericytoma (angioblastic meningioma). peripheral hemangiopericytoma and acoustic schwannoma. A comparative immunohistochemical study. AmerJSurg Parhol 13: 251-261
42. lwaki T, Fukui M, Tsuneyyoshi M ( 1 988) Hemangiopericytoma of the meninges: Clinicopathologic and immunohistochemical study. Clin Neuropathol 7: 93-99 43. Mena H, Ribas JL, Pezeshkpour G, Parisi JE. Cowan D (1 989) Central nervous system hemangiopericytoma. J Neuropathol Exp Neural 48: 358 (abstr) 44.Mapstone T, Wongmongkolrit T, Roessman U, Ratcheson R (1983) lntradural chondroma: A case report and review of the literature. Neurosurg 12: 11 1-114 45.Janisch W, Schreiber D, Guthert H (1988) In: Neuropafhologie-Tumoren des Nervensystems, pp. 405406, G.Fischer: Stuttgart 46. Parker JR, Zarabi MC, Parker JC (1989) lntracerebral mesenchymal chondrosarcoma.Ann Clin Lab Sci 19: 401607 47. Brooks JJ, LiVolsi VA, Trojanowski JQ (1987) Does chondroid chordoma exist? Acta Neuropathol (Bed) 72: 229-235 48. Cybulski GR, Russell EJ, D’Angelo CM, Bailey OT (1985) Falcine chondrosarcoma: Case report and literature review. Neurosurg 16: 412-415 49. Hruban RH, May M, Marcove RC, Huvos AG (1990)Lumbo-
sacral chordoma with high-grade malignant cartilaginous and spindle cell elements. Am J Surg Parhol 14: 384-389
50. Swanson PE, Lillemoe TJ, Manivel JC. Wick MR (1990) Mesenchymal chondrosarcoma. An immunohistochemical study. Arch Parhol Lab Med 114: 943-948 51. Lam RMY, Malik GM, Chason JL (1981) Osteosarcoma of meninges. Am J Surg Pafhol 5: 203208 52. Amine ARC, Sugar 0 (1976) Suprasellar osteogenic sarcoma following radiation for pituitary adenoma. J Neurosurg 44: 88-91 53. Kawamoto EH, Weidner N, Agostini RM Jr, Jaffe R (1987) Malignant ectomesenchymoma of soft tissue. Cancer 59: 1791-1802 54. Berry AD 111, Kepes JJ, Trombley IK, Chang HH, Robb JA (1988) Myxomas and other myxoid tumors of the central nervous system and its coverings. Differential diagnostic considerations.J Neuroparhol Exp Neurol 47: 379 (abstr) 55.Hufnagel TJ, Kim JH, True LD, Manuelidis EE (1989) Immunohistochemistryof capillary hemangioblastoma. Am JSurg Pafhol 134: 271-275 56. Becker I, Paulus W, Roggendorf W (1989)Histogenesis of stromal cells in cerebellar hemangioblastomas. Am J Parhol 134: 271-275 57. Theunissen PHMH. Debets-Te Baerts M, Blaauw G (1990) Histogenesis of intracranial hemangiopericytoma and hemangioblastoma.Acta Neuropathol (Berll 80: 6871 58. Scheithauer EM. Egbert B (1978) Ewing‘s sarcoma of the spinal epidural space: Report of two cases. J Neurol Neurosurg Psychiat 41 : 1031-1 035 59. Moll R, Lee I, Gould VE. Berndt R, Roessner A, Franke WW (1987) lmmunocytochemical analysis of Ewing’s tumor.
K. Jellinger and W. Paulus: Mesenchymal, non-meningothelial tumors
Patterns of expression of intermediate filaments and desmosomal proteins indicate cell type heterogeneity and pluripotential differentiation Am J Parbol 127 288-304 60 Jakata SM Marsden HE. lngram L (1988) Primary rhabdoid tumor of the brain Vfrchows Arch Pathol Anat 412 393397 61 Schmidt D, Leuschner I, Harms D, Sprenger E, Schafer H (1989) Malignant rhabdoid tumor A morphological and flow cytometric study Parh Res Pract 184 202-21 0 62 Thibodeau L, Ariza A, Piepmeier J M (1988) Primary leptomeningeal sarcomatosis J Neurosurg 68 802-805
a7
REVIEW Mesenchymal, Non-Meningothelial Tumors of the Central Nervous System
Kurt Jellinger 1 and Werner Paulus 2
of Clinical Neurobiology, Lainz-Hospital, A-1 130 Vienna, Austria 2 Department of Pathology, University of Wurzburg, School of Medicine, D-8700 Wurzburg, Federal Republic of Germany 1 Ludwig Boltzmann Institute
The spectrum of non-meningothelial rnesenchymal tumors that may arise within the central nervous system is presented, based on the current classification of soft tissue tumors. Among malignant types, hemangiopericytoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma are the most frequent ones. Rare tumor entities are mentioned. As in soft tissue sarcomas, diagnosis is mainly based on light and electron microscopy, while immunohistochemistry can improve accuracy of diagnosis. Introduction
In the World Health Organization (WHO) classification of CNS tumors (l),mesenchymal, non-meningothelial tumors were listed among various headings: I. Tumors of meningeal and related tissues, including A. Meningeal sarcomas, 1. fibrosarcoma, 2. polymorphic cell sarcoma, 3. primary meningeal sarcomatosis; 11. Xanthomatous tumors (fibroxanthoma and xanthosarcoma); 111. Others (fibroma, chondroma, mesenchymal chondrosarcoma); IV. Other malformative tumors and tumor-like lesions (lipoma). The new version of the WHO Classification, separating benign and malignant tumors, will be partly based on modifications proposed by Scheithauer (2) which, in part, refer to the histologic classification of soft tissue tumors by Enzinger and Weiss (3). The occurrence of most of these tumor types in the CNS and its coverDedicated to the memory of our late friend Lucien Rubinstein Corresponding author: Dr. K. Jellinger, Ludwig Boltzmann Institute of Clinical Neurobiology, Lainz-Hospital. Wolkersbergenstrasse 1, A-1 130 Wien. Austria Tel. +43 (222) 801 10, ext. 3431; Fax +43 (222) 804 5401
ings is well documented (Table 1). Diagnosis is mainly based on light microscopy and may be supported by electron microscopy (4). Immunohistochemistry is often of limited value, except for tumors of muscle tissue or vascular origin (2-6; Table 2). Before diagnosing primary CNS sarcoma, both gliosarcoma and metastatic sarcoma have to be excluded. Tumors of Fibrous nssue and Fibrohistiocytic Tumors
1 . l . Fibroma Benign intracerebral tumors composed of fibrocytes or fibroblasts with variable amounts of collagen and blood vessels often showing degenerative changes (mucoid, calcification) are rare; about 15 cases have been reported, most in the first decades of life. They may be attached to the dura or are situated in deeper brain areas without relation to the dura (7). They are to be distinguished from fibrous meningioma, gliofibroma, and intracerebral schwannoma. Intracranial variants include single instances of angiofibroma (8), and myofibroblastoma (9). 1.2. Fibrous histiocytoma (fibroxanthoma) This benign tumor occurring in the skin is composed of a mixture of fibroblastic and histiocyte-like cells arranged in a storiform pattern, and accompanied by varying numbers of inflammatory and/or giant cells. Its primary occurrence in the CNS is debatable, since positive reaction with GFAP in most tumors of this type may suggest a glial neoplasm referred to as pleomorphic xanthoastrocytoma (PXA)(10), while some authors consider it a mesenchymal tumor identical with extracranial fibrous histiocytoma (FH), partly with astrocytic invasion (11). Only four well-documented totally GFAP-negative FH have been reported within the CNS (12,12a). 1.3. Fibrosarcoma (FS) Malignant mesenchymal neoplasms composed of fibroblasts with fascicular arrangement that show no other evidence of cellular differentiation are rarely observed in the CNS. In earlier studies, this tumor has been overdiagnosed and a number of cases have
1
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80
Table 1 Mesenchymal, non-meningothelial tumors of the CNS MALIGNANT
BENIGN Fibrohisfiocytic tumors and tumors of fibrous tissue
Fibrosarcoma Malignant fibrous histiocytoma storiform-pleomorphic myxoid giant cell type (?) inflammatory
Fibroma Variants: Angiofibroma * Myofibroblastoma Fibrous histiocytoma (Fibroxanthoma)
Tumors of adipose tissue Liposarcoma
Lipoma Variant: Angiolipoma Tumors of muscle tissue
Leimyosarcoma R habdomyosarcoma embryonal botryoid (?) alveolar pleomorphic (?)
Leiomyoma (?I Variant: Glomangiomyoma
Tumors of blood vessels Angiosarcoma Kaposi's sarcoma (?) Hemangiopericytoma
Epithelioid hemangioendothelioma
Tumors of cartilage and bone-forming tissue Chondrosarcoma myxoid differentiated mesenchymal Osteosarcoma
Chondroma / Osteochondroma Osteoma / Osteoblastoma
Tumors of pluripotential mesenchyme Malignant mesenchymoma (?) Ectomesenchymoma * Tumors of uncertain or disputed origin Ewing's sarcoma Rhabdoid tumor
Myxoma Hernangioblastoma
Meningeal sarcomatosis Unclassified Sarcoma ONS
only single cases reported /
(?I occurrence in the CNS uncertain
been reclassified as malignant fibrous histiocytoma (MFH)(3). Transitions between FS and MFH may occur (3,4). FS is ultrastructurally composed only of fibroblasts and reacts with no specific marker except for vimentin (4). FS may arise from the dura, the lep-
tomeninges and, rarely, within the brain (13) and choroid plexus (14). It may occur spontaneously, in neurofibromatosis, and is not uncommon following cranial radiation often with long latencies (14).
K. Jellinger and W. Paulus: Mesenchymal. non-rneningothelial tumors
1.4. Malignant fibrous histiocytoma (MFH)
This commonest type of soft tissue sarcoma in adults arising preferentially in the retroperitoneum and in deep soft tissues is composed of a mixture of round and spindle cells, giant cells and optional xanthomatous cells. Five subtypes are separated (3): a) storiform-pleomorphic (most frequent); b) myxoid (myxofibrosarcoma);c) giant cell type; d) inflammatory, e) angiomatoid. About 20 cases of primary intracranial MFH have been described (15) including 6 personal ones from a series of 19 primary CNS sarcomas (13). They often arise within the meninges or are connected with them, while some are intracerebra1 without any relationship to the coverings. The age range is 13 to 76 years. MFH may occur following irradiation or after glioma exstirpation (16). The ultrastructural hallmark is heterogeneity of cell types including fibroblast-like, histiocyte-like, myofibroblast-like, undifferentiated cells and intermediate forms of these, some being predominantly fibroblastic (4,17). The histogenesis of MFH is under discussion, since some of the "histiocytic markers", e.g. alpha-1-antitrypsin, turned out to be rather nonspecific, and more specific mono-histiocytic markers are negative or inconsistently expressed by tumor cells (4,13,18).They are positive for vimentin, negative for desmin and S-100 protein and show a heterogeneous pattern of intermediate filament proteins with occasional expression of cytokeratin (4,19). There may be large intratumoral bulks of GFAP positive cells and processes (Fig. 1) that make separation of MFH from pleomorphic xanthoastrocytoma or gliosarcoma difficult (20,21). Differential diagnosis includes many pleomorphic neoplasms, e.g. liposarcoma, osteo- and chondrosarcoma, leio- and rhabdomyosarcoma, fibrosarcoma, carcinoma, malignant meningioma, and schwannoma. The prognosis of intracranial MFH is poor, with rapid local recurrence, distant metastases and survival not exceeding 10 months (13-17). Tumors of Adipose Tissue
2.1. Lipoma Rare localized masses of lipid tissue represent less than 0.5% of intracranial and 0.4% of spinal axis tumors. They occur at any age and are frequently found in the midline, over the corpus callosum (about SO%), the quadrigeminal plate, hypothalamus, in the cerebellopontine angle, and spinal cord. While most of the spinal lipomas invade the intradural space, a rare subtype termed angiolipoma (angiomyolipoma) is restricted to the epidural space (Fig. 2), but intracranial forms have also been reported. This tumor contains both vascular (angioid) and mature adipose elements (22). 2.2. Liposarcoma Liposarcoma, next to FMH the most common soft tissue sarcoma in adults, includes: a) well differentiated,
81
b) myxoid (most common), c) round cell, and d) pleomorphic forms. Development from pre-existing lipoma is extremely rare. Immunohistochemistry may help in differential diagnosis, since adipocytes and lipoblasts are often S-100 protein positive. Only one intracranial case in the meninges has been reported (23). Tumors of Muscle Tissue
3. I . Benign forms Benign tumors of smooth muscle (leiomyoma) and of striated muscle (rhabdomyoma) are extremely rare in the CNS (24), while leptomeningeal rhabdomyomatosis (heterotopic skeletal muscle in the leptomeninges of the posterior fossa) is not infrequent (25). Single cases of sellar angiomyoma or glomangioma with organoid structure of tumor cells reacting with actin/myoglobin were observed (26). 3.2. Leiomyosarcoma (LMS) Primary intracranial LMS is exceedingly rare (13,14). It is located in the meninges of sellar or suprasellar region (27) or in the dura (28). Histologically, LMS is composed of short fascicles of elongated cells often showing prominent perinuclear vacuoles with nuclear indentation (Fig. 3): Immunostaining reveals positivity for vimentin, muscle-specific actin, while desmin may be negative (4,s). For differential diagnosis that includes all tumors composed of fascicles of spindle cells, electron microscopy is useful (4). 3.3. Rhabdomyosarcoma (RMS) This most common soft tissue sarcoma of childhood, arising predominantly in the head and neck region, only rarely occurs as primary CNS neoplasm. About 35 cases have been reported occurring in all ages and in various CNS locations, most commonly in posterior fossa in children and in cerebral hemispheres of adults (13,29). There are four types: a) embryonal RMS resembling developing muscle with densely packed small round cells, b) botryoid type of embryonal RMS with polypoid growth and abundant mucoid-myxomatous stroma, c) alveolar RMS with aggregates of poorly differentiated cells showing formation of honey-comb like spaces, and d) pleomorphic type that is difficult to distinguish from other pleomorphic sarcomas. Most intracranial RMS contain rhabdomyoblasts with eosinophilic cytoplasm and areas of poorly differentiated cells, only part of which show cross-striation. Immunohistochemistry reveals frequent expression of vimentin, desmin (90%), and myoglobin (66%), but only in a small percentage of undifferentiated cells (30). Ultrastructural demonstration of myofilaments may be of diagnostic value in cases being negative for myoglobin (4). Differential diagnosis includes Ewing's sarcoma, MFH, teratoma, medullomyoblastoma. Meningeal
K. Jellinger and W. Paulus: Mesenchymal. non-meningothelial tumors
82
RMS is to be separated from meningeal extension of parameningeal head and neck tumors. Tumors of Blood Vessels
While the classification of soft tissue tumors and the old WHO classification of CNS tumors include (hem) angiomas as benign vascular neoplasms, they represent vascular malformations and, therefore, have to be excluded. 4.1. Hemangioendothelioma
This tumor considered of intermediate malignancy between hemangioma and angiosarcoma, has been rarely observed as primary CNS epithelioid hemangioendothelioma (3,31). Usually present in deep soft tissues and parenchymal organs, it is composed of strands or solid nests of rounded to spindled endothelial cells with intracellular miniature lumina and myxoid or hyaline stroma. Tumor cells are positive for factor VIII-related antigen (F-VIII-RA) and show ultrastructural evidence of Weibel-Palade bodies. 4.2. Angiosarcoma
Single instances of angiosarcoma have been observed in the spinal cord meninges after chordotomy (32) and within the brain (33). Tumor cells are inconsistently immunolabeled by F-VIII-RA and the lectin UEA-I (4), but more sensitively by RMS-120, a monoclonal antibody specific for endothelial cells (34). Neoplastic angioendotheliosis is now recognized as an intravasal (angiotropic) malignant large cell lymphoma mostly of B-cell type (35,36). 4.3. Kaposi's sarcoma The existence of primary CNS involvement by Ka-
posi's sarcoma is questionable. In all African cases without AIDS and in a few AIDS cases reported so far, spread of tumor into the CNS was accompanied by involvement of the lungs or other organs suggesting a metastatic process (37). 4.4. Hemangiopericytoma (HPC) This tumor occurs in both soft tissues, head and neck including orbit and sinonasal areas, and in intracranial and intraspinal spaces, where it has been regarded as a subtype of "angioblastic meningioma" (14). It accounts for 1 to 7% of meningeal neoplasms. Its histologic pattern of high cellularity with compact arrangement of plump, polygonal cells with illdefined cytoplasm in solid masses or sheets and around slit-like or "staghorn" vasculature lined by single endothelial cells, a variable reticulin network, and frequent mitoses is identical to HPC at other sites. EM appearance of CNS and soft tissue HPC is also largely identical and lacks interdigitating processes and well-developed desmosomes typical of meningiomas (2-4, 38-40). They further lack tight whorls, psammoma bodies and EMA (epithelial membrane antigen) immunoreactivity that are common features of meningiomas, but show abundant extracellular basal-lamina like material considered a diagnostic EM feature of HPC (38). Tumor cells are positive for vimentin and occasionally for desmin, muscle actin, alpha-actinin, laminin and type IV collagen (2, 38-41). The tumors are attached to the meninges and show compressive or invasive growth, but their topographic distribution, at least in some series, differs from common meningiomas, with more frequent involvement of the tentorium and infratentorial space (40,42), while others saw no topical differences (2,14). Meningeal HPC show aggres-
Table 2 lmmunohistochemistry of mesenchymal, non-meningothelial tumors of the CNS (2-6)
Tumor type Fibrous histiocytoma Mal.fibr.histiocytoma Fibrosarcoma Liposarcoma Leiomyosarcoma R habdomyosarcoma Angiosarcoma Hemangiopericytoma Chondrosarcoma Ewing's sarcoma Meningioma
Kmentin
Desmin
+ +
GFAP
Cker
NF
€MA
+
+
+
S700
FBRA
Mact
+
t
+
+
(+)
t
+ + t
(+)
t
GFAP glial fibrillary acidic protein; Cker cytokeratin; NF neurofilament protein; € M A epithelial membrane antigen; FBRA factor VIII-related antigen; Mact muscle actin + usually positive; (+) positive in some cases; t focal positivity in occasional cases
83
1
2
3
4
5
6
7
8 Figure 1 Islands of pleomorphic astrocytes within a leptomeningeal malignant fibrous histiocytoma. Female, 55 yrs. GFAP; 2 Epidural angiolipoma at Th 5-7 causing progressive paraplegia. Female, 70 yrs, H&E; 3 Meningeal myxoid leiomyosarcoma. Note perinuclear vacuoles. Male, 4 yrs. muscle actin; 4 Mesenchymal chondrosarcoma of the tentorium. Male, 17 yrs, H&E; 5 Malignant ectornesenchymoma. A number of rhabdomyoblasts react with desmin. Female, 18 yrs; 6 Malignant ectomesenchymoma (same case) with scattered neoplastic ganglion cells. Neurofllament protein; 7 Epidural parietal Ewing's sarcoma infiltrating the dura mater. Female, 19 yrs, PAS; 8 Primary meningeal sarcomatosis with focal infiltration of the cerebral cortex. Female, 29 yrs, Vimentin.
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K. Jellinger and W. Paulus: Mesenchymal, non-meningothelialtumors
sive behavior, with recurrence rates between 20 and 80% and metastatic rates between 10 and 55%, and median survival between 58 and 84 months (2,43). Although some authors stress their classification as meningiomas (14), central HPC appears to represent a distinct entity probably originating from polyvalent mesenchymal cells and not from arachnoidal cap cells. Tumors of Cartilage and Bone-Forming Tissue
5.1. Chondroma and osteochondroma While the majority of benign cartilage tumors arise from the base of the skull, primary chondromas in the brain and meninges represent rare forms of extraosseous cartilagineous tumors. They may be attached to the dura over the cerebral convexities (44) or occur in the leptomeninges or choroid plexus (45). Some meningeal lesions contain bone mixed with cartilage (osteochondroma). They are to be separated from mixed tumors (teratoma, glioma) with cartilagineous areas. 5.2. Osteoma and osteoblastoma Extraosseous tumor-like lesions of differentiated bone-forming tissues in the CNS are exceedingly rare and the majority of these lesions are reactive bone formations or mixed mesenchymal tumors with bone and cartilage such as intracerebral osteochondrofibroma or osteolipoma, although cerebral or meningeal osteomas and osteochondrornas have been described (45).
5.3. Chondrosarcoma (CS) These rather frequent malignant cartilage tumors usually arising in bone and soft tissue may also occur in the craniospinal space. About 60 cases have been reported (14,46), including two personal cases (13). Three histologic subtypes are separated: a) Myxoid chondrosarcoma (chordoid sarcoma), a lobulated mass composed of.small chondroblasts and a myxoid matrix often resembling chondroid chordoma (47). Only single circumscribed or diffuse intracerebral and meningeal instances have been reported (14,47). b) Differentiated chondrosarcoma is extremely rare
at extraosseous locations and shows predominance of cartilaginous elements with few myxoid components. It occurs in the parasellar region, cerebellopontine angle or falx and is believed to arise from cartilaginous synchondroses or ectopic cartilage within brain and meninges (48). Distinction from chondroid chordoma considered by some as "low grade CS" (47) can be made by negative reaction with cytokeratins and EMA (chordoma) and S-100 protein
(cartilaginous areas) (49). Differentiated CS may develop extracranial metastases.
c) Mesenchymal chondrosarcoma is a malignant tumor composed of sheets of undifferentiated cells and interspersed islands of atypical chondroid or differentiated hyaline cartilage. The compact cell aggregates are composed of fusiform cells showing occasional palisading, separated by numerous thin-walled vascular spaces (Fig. 4). The small cells fail to express S-100 protein, but may stain for Leu-7 antigen and some for NSE (neuron specific enolase) (50). Craniospinal meninges are the most frequently reported extraskeletal sites, representing more than half of all cranial/intracranial CS (46,SO). Tumors without cartilagineous differentiation may be mistaken for HPC or may mimick neuroepitheial neoplasms, as tumor cells may form Homer-Wright-like rosettes. Immunohistochemistry is not overly helpful in the differential diagnosis to other small round cell neoplasms (50). Prognosis is poorer than in non-mesenchymal CS. The tumor tends to recur and has a high propensity to develop extracranial metastases. 5.4. Osteosarcoma (0s) Histology ranges from fibrosarcoma- or MFH-like (fibroblastic 0 s ) to extremely cellular neoplasms having irregular or spindle cell pattern (osteoblastic OS), while atypical cartilage (chondroblastic 0s) or giant cells (osteoclastic/giant cell 0 s ) may rarely become a predominant feature. 0 s arising primarily from the meninges is exceptional (Sl), and should be separated from that originating from the skull. Radiationinduced 0 s of pituitary fossa was observed (52). Other rare sarcomas with osseous components were reported in cerebellar vermis or fourth ventricle (see 45). Tumors of Pluripotential Mesenchyme
6.1. Malignant mesenchymoma and ectomesenchymoma This is a small and heterogenous group of sarcomas that exhibit two or more distinct and differentiated mesenchymal components besides the fibrous element (333). Whether tumors fulfilling these criteria do arise primarily in the CNS is unknown. We observed a primary CNS malignant ectomesenchymoma consisting of a mixture of embryonal RMS with neoplastic ganglion cells (Fig. 5,6). Tumors of Uncertain or Disputed Origin
7.1. Myxomn This benign tumor, histologically similar to Wharton's jelly of the umbilical cord, appears to be extremely rare in the CNS, but several types of meningeal tumors may mimick its appearance (54).
K. Jellinger and W. Paulus: Mesenchymal, non-meningothelial tumors
7.2.Hemangioblastoma Cerebellar hemangioblastomas are composed of endothelial cells, pericytes, and stromal cells. The supratentorial form was considered a subtype of angioblastic meningioma (14). Stromal cells are antigenetically polymorphous: they may express cytokeratin, GFAP, vimentin, Leu M1, Leu-7, actin, erythropoietin, S-100 protein and NSE (55). The pattern of antigen expression of the stromal cells does not allow identification of a definite histogenesis, but positivity of synaptophysin and a broad spectrum of neuropeptides suggests a neuroendocrine component of this tumor (56,57). 7.3.Ew-ng’s sarcoma Extraskeletal tumors histologically indistinguishable from Ewing’s sarcoma of bone have been documented as epidural masses in the cranial cavity and spinal canal predominantly in adolescents and young adults (58). The tumor is composed of densely packed, uniform, round or ovoid, lymphocyte-like cells with scanty cytoplasm often containing glycogen (Fig. 7). Prominent features include lobular pattern, lack of reticulin fibers, and rich vascularization. Usually vimentin is the only intermediate filament protein, but clusters of cells positive for cytokeratin and neurofilament proteins have been found (59), indicating that they are derived from a primitive pluripotent cell that may differentiate along different pathways. Epidural tumor masses in the spinal canal may show extensions to paraspinal musculature or distant metastases. 7.4. Rhabdoid tumor
85
Sarcoma, Type not Otherwise Specified
Some tumors without recognizable light microscopic and ultrastructural differentiation and with no other specific immunohistochemical marker, apart from vimentin, are regarded as undifferentiated sarcomas provided that other tumor types are excluded. References 1.
Zulch KJ (1979) Histological typing of turnours of the central nervous s y s t e m . In: International Histological Classification of Turnours, WHO, No 21, Geneva
2.
Scheithauer B W (1990) Tumors of the meninges: Proposed modification of the World Health Organization classification. Acta Neuropathol (Berl) 80: 343-354
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Enzinger FM, Weiss SW (1988) Soft Tissue Tumors. 2nd ed., C.V. Mosby: St. Louis
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Fisher C (1990) The value of electronmicroscopy and immunohistochemistry in the diagnosis of soft tissue sarcomas: A study of 200 cases. Histopathol 16: 441-454
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Miettinen M (1988) Antibody specific to muscle actins in the diagnosis and classification of soft tissue tumors. Am J Pathol 130: 205-21 5
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Manivel JC, Wick MR, Swanson PE, Scheithauer B (1987) Epithelial membrane antigen in sarcomas. Lab lnvesr 56. 46 (abstr)
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Palma L, Spagnoli LG. Yusuf MA (1985) lntracerebral fibroma: light and electron microscopic study. Acta Neurochir (Wien) 77: 152-156
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10 Kepes JJ, Rubinstein LJ, Ansbacher L, Schreiber DJ (1989) Histopathologic features of recurrent pleomorphic xanthoastrocytoma: Further corroboration of the glial nature of this neoplasm. A study of 3 cases. Acta Neuropathol (Berl) 78: 585-593
Rare extrarenal rhabdoid tumors may primarily arise within the CNS (60). They are composed of cellular sheets of undifferentiated monomorphic cells characterized by globular perinuclear inclusions that contain whorls of intermediate filaments. They stain for vimentin, but occasionally also for cytokeratin, desmin, EMA, NSE, and S-100 protein (61).
11 Paulus W, Peiffer J (1988) Does the pleomorphic xanthoastrocytoma exist? Problems in the application of imrnunological techniques to the classification of brain tumors. Acta Neuropathol (Berll 76: 245-252
Primary Meningeal Sarcomatosis
12a.Nakamura Y, Becker LE (1985) Meningeal tumors of infancy and childhood. Pediat Pathol 3: 341-358
Sarcomas arising from and diffusely infiltrating the meninges without forming large circumscribed tumor masses are rare and mainly occur in infants, children and rarely in adults (62). They may arise multifocally or show diffuse cerebrospinal spread with encasement of the spinal cord, and frequently invade the brain. Small lymphocyte-like, round or fusiforrn cells with dark nuclei and scanty cytoplasm represent the most common histologic appearance. Vimentin is usually the only intermediate filament (Fig. 8). Rhabdomyomatous and chondromatous sarcomatoses have been described. Diagnosis of meningeal sarcomatosis is only possible by exclusion of metastases of extraneural sarcoma, lymphoma, medulloblastoma, and other small cell neoplasms.
12. Kepes JJ (1979) ‘Xanthomatous* lesions of the central nervous system: Definition, classification and some recent observations. Prog Neuropathol 4: 179-213.
3. Paulus W, Slowik F, Jellinger K (1991) Primary intracranial sarcomas: Histopathologic features of 19 cases. Histopatho/ 17 (in press) 4. Russell DS, Rubinstein LJ (1989) In: Pathology of Turnours of the Nervous System, 5th ed., pp. 473-479, Edward Arnold: London
5. Berry AD, Reintjes SL, Kepes JJ (1988) lntracranial malignant fibrous histiocytoma with abscess-like tumor necrosis. J Neurosurg 69: 780-784 16. Paulus W, Peiffer J, Grote E (1989) lntracranial malignant fibrous histiocytoma a t site of previously excised low grade glioma. Acta Neurochir (Wen) 99: 161-165 17. Sima AAF, Ross R. Hoag G, Rozdilsky B, and Diocee M (1988) Malignant intracranial fibrous histiocytoma. Histologic, ultrastructural immunohistochemical studies of t w o cases. Can J Neurol Sci 13: 138-145
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18. Roholl PJM, Kleyne J, Prine MEF (1989) Immunologic marker analysis of normal and malignant histiocytes. A comparative study of monoclonal antibodies for diagnostic purposes. Am J Clin Parhol 89: 187-194
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1366 20. Ng HK, Poon WS (1990)Gliosarcoma of the posterior fossa with features of a malignant fibrous histiocytoma. Cancer 65:1161-1166 21. Ho KL (1990) Histogenesis of sarcomatous components of the gliosarcoma: An ultrastructural study. Acfa Neuropathol (Berll 81: 178-187
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