AUTHOR(S): Salcman, Michael, M.D.; Scholtz, Herman, M.D.; Kristt, Donald, M.D.; Numaguchi, Yuji, M.D. Division of Neurological Surgery (MS, HS), Division of Neuropathology (DK), and Division of Neuroradiology (YN), University of Maryland School of Medicine, Baltimore, Maryland Neurosurgery 31; 344-348, 1992 ABSTRACT: INTRACRANIAL CARTILAGINOUS TUMORS are unusual lesions, of which myxoid chondrosarcoma is the rarest. We describe this tumor arising from the falx in a 28-year-old woman treated at recurrence with a second operation and a radiation implant. The behavior of classic chondrosarcoma and mesenchymal chondrosarcoma is also reviewed. KEY WORDS: Cartilage tumor; Chondrosarcoma; Interstitial radiation; Meningioma Intracranial tumors of cartilaginous origin represent less than 0.16% of all primary brain tumors (5). More than 126 intracranial chondromas have been reported (30) , as well as just over 50 chondrosarcomas (13). Of the latter, only 6 myxoid chondrosarcomas have been studied. We have recently had the opportunity to examine such a tumor with electron microscopy, immunocytochemistry, and magnetic resonance imaging studies. A review of the literature indicates that such a tumor arising above the skull base is extremely rare (9). CASE REPORT A 28-year-old right-handed white woman, 30 weeks pregnant, had a 2-month history of progressive right-sided weakness, slowed speech, and severe frontal headaches. She also noted difficulty with position sense in the right foot. A computed tomographic (CT) scan revealed a large, 7 × 5 × 4 cm multilobulated lesion in the parafalcine region on the left. The tumor was isodense and did not enhance well with contrast. A magnetic resonance imaging (MRI) scan showed the lesion to be a welldemarcated hypointense mass on T1 with homogeneously high intensity on T2 images (Fig. 1), and the diagnosis of meningioma was considered. At surgery, the lesion was a multilobulated white mass in a grape-like cluster with a mucoid consistency and did not appear to have any attachment to either the brain or the falx. Indeed, it appeared as if the tumor had been poured into the space between these structures, and it was easily sucked out without significant bleeding. On light microscopy (Fig. 2), the tumor consisted of uniform round or oblong cells arranged in cords and strands in an abundant myxoid stroma. The

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specimen from the second resection was more homogeneously cellular. The pleomorphic nuclei were vesicular with only occasional nucleoli. The small cuff of cytoplasm was deeply eosinophilic and sometimes indented the nucleus. Occasionally the cytoplasm was bubbly, but typical physaliferous cells were absent. In some locations, the mitotic rate was high. In the first specimen, there were many foci suggestive of cartilaginous differentiation, but without frank cartilage formation. In the cytoplasm of some tumor cells, periodic acid-Schiff-positive material was present, which was digested with diastase, a reaction typical of glycogen. The myxoid background matrix stained with Alcian blue and was partially digested by hyaluronidase. In the original biopsy, hematoxylin and eosin-stained sections showed foci with a slightly bluish tinge to the background, reminiscent of immature cartilage. Reticulin staining was present around the vessels, but not between the tumor cells. On electron microscopy (Fig. 3), the tumor demonstrated intermediate filaments in paranuclear whorls and bundles and a prominent Golgi complex. Filaments were also scattered among the abundant mitochondria and rough endoplasmic reticulum (RER). The mitochondrial-RER complex described in chordomas was absent, and there were no lipoblasts or filamentous specializations suggestive of muscle differentiation. Where cells contacted one another, no complex interdigitations were seen nor were any true desmosomes observed. The cells were not surrounded with basement membrane. Immunoperoxidase staining supported the mesenchymal or sarcomatous nature of the lesion. The tumor was negative for glial fibrillary acidic protein, cytokeratin, epithelial membrane antigen, and S-100. The tumor was strongly positive for vimentin in a diffuse or focal cytoplasmic localization corresponding to the filament distribution seen on electron microscopy. The patient was discharged without any further neurological deficit. A follow-up MRI scan 8 months after surgery demonstrated minimal contrast enhancement in the surgical bed. Ten months after surgery, she had a generalized seizure and right leg weakness. The MRI scan at that time showed recurrent tumor in the left parasagittal area (Fig. 4). At the second operation, a 3 × 2 cm tumor was resected, and at the same procedure, multiple 125I radioactive seeds were implanted into the tumor cavity (Fig. 5). Macroscopically and microscopically the tumor had the characteristics described above. Postoperatively, the patient was discharged with a mild right hemiparesis that resolved with rehabilitation. A follow-up MRI scan (Fig. 6) 4 months after the second operation showed a small area of abnormal enhancement in the region of the cingulate gyrus, but a second scan 8 months after the second operation showed no evidence of residual tumor. The patient remained asymptomatic 12 months after the implant procedure and 22 months after diagnosis. DISCUSSION

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Neurosurgery 1992-98 August 1992, Volume 31, Number 2 344 Extraskeletal Myxoid Chondrosarcoma of the Falx Case Report

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subdural space and attached to the tentorium (1,2,7,27, 30) . Patients between the second and sixth decade of life are the most frequently affected (27,33). No definite sexual predominance has been reported (28,33). This tumor has a better prognosis than mesenchymal chondrosarcoma, although a meningeal case with metastatic spread to the viscera was described in 1972 (37), and similar cases with osseous metastases have been reported on several occasions (10,13). Nevertheless, metastases are seen less frequently with this tumor than with the mesenchymal variety. Fifty percent of the skull base tumors demonstrate calcification on plain film radiography as well as erosion, and this may lead to confusion with meningioma (4,20). There is usually no tumor stain by angiography, although the tumor enhances minimally to moderately on CT scan (4,33). On MRI scans, the tumor appears more hyperintense on the T2-weighted image than on the T1-weighted image. Grossly, there is no adhesion to the brain, and histologically there is a greater production of mature cartilage than is seen with mesenchymal chondrosarcoma (9). By electron microscopy, the tumor demonstrates cytoplasmic glycogen (22). Although little is known concerning the etiology of these tumors, a radiation-induced chondrosarcoma of the cerebellum has been described in a 23-year-old man treated twice in childhood for astrocytoma (7). The extent of surgical resection is the critical therapeutic factor in classic chondrosarcoma; the effectiveness of conventional radiation is equivocal and recurrence is common. Suit et al. (35) treated 6 chordomas, 3 chondrosarcomas, and 1 neurofibroma of the skull base and cervical spine with a combination of high-energy x-rays (photons) and a 160-MeV proton beam. Local control in all but one case was achieved without neurological sequelae using high doses up to 73.3 Gy, in a follow-up period of up to 6 years. Kondziolka et al. (15) reported the use of gamma knife stereotactic radiosurgery in 6 patients, 4 with chordoma and 2 with chondrosarcoma of the skull base, as an adjuvant treatment in 5, and as the primary treatment in 1. All of the tumors were less than 30 mm in diameter and at least 5 mm from the optic nerve or from the chiasm. A total dose of 20 Gy was given to the tumor margin. Three patients had improvement in neurological deficit, and no patient experienced a further deficit. No tumor showed radiographic signs of progression during the follow-up period (mean, 22 mo). A 5-year actuarial local control rate of 82% was reported by Austin-Seymour et al. (3) with the use of fractionated high-dose postoperative radiation delivered with a 160-MeV proton beam in 68 patients with chordomas and chondrosarcomas of the skull base at a median tumor dose of 69 cobalt Gy equivalents. All of these authors have concluded that high dose rate or high energy treatment is superior to conventional fractionated radiation. In addition to the type of radiation treatment, the length of survival in classic chondrosarcoma correlates with the histological grade of the tumor and how resectable it is. Myxoid chondrosarcoma represents a tumor of

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Intracranial cartilaginous tumors usually arise at the skull base from pluripotential mesenchymal cells or from embryonal cartilaginous rests (28,31,38) associated with the cartilaginous development of bone in such locations as the paranasal sinuses, parasellar area, and the spheno-occipital synchondroses. In addition to chondromas, the other cartilaginous tumors include chondrosarcomas, mesenchymal chondrosarcomas, and myxoid chondrosarcomas (9,13). These tumors are usually solitary lesions, but the occurrence of multiple systemic enchondromas and hemangiomas (Maffucci's syndrome) with intracranial chondrosarcomas has been described (18). Approximately 25% of extraosseous or soft tissue chondrosarcomas involve the meninges (23), usually at the skull base. However, mesenchymal chondrosarcomas have been described as arising most frequently above the base (8,12,14). Although both chondrosarcomas and mesenchymal chondrosarcomas have been reported to arise from the falx (8,22), no case of falcine myxoid chondrosarcoma has been previously described in detail. The three types of intracranial chondrosarcoma need to be carefully delineated in view of important differences in prognosis and therapeutic approach. Mesenchymal chondrosarcoma was first defined as a separate nosological entity in l959 (19) and represents almost half of intracranial cartilaginous sarcomas (13,24,38,39). By 1978, 8 mesenchymal chondrosarcomas of the meninges had been described, 5 of which were spinal (31), including an intracranial example without apparent attachment to either the bone or the meninges. As in our case, mesenchymal cells that sheath the perforating blood vessels were the presumed site of origin. In the spine, mesenchymal chondrosarcoma demonstrates a clinical behavior similar to that of the intracranial variety (12). The patients have an average age of 25 years, younger than those with other cartilaginous sarcomas (14), and a slight predominance in women has been reported (16). The prognosis is worse than that observed with ordinary chondrosarcoma (12), and distant metastases have been described (14,16). The tumors are frequently vascular and can be misdiagnosed on angiography either as arteriovenous malformations or meningiomas, particularly of the angioblastic type (12,26,31). The histological picture is highly distinctive and the appearance by electron microscopy has been described on several occasions (12,14,26,36,39) ; the tumors are glycogen-negative and demonstrate collagen fibrils in their mesenchymal matrix (12,26,39). The 5-year survival rate is about 40%, and only occasional long-term survivors have been reported. Radiation therapy is routinely added to surgery without real evidence that it prolongs survival. Some cases have benefitted through the addition of chemotherapy (12,14). Adriamycin and methotrexate have been employed as adjuvant agents. Preoperative embolization may be of value in these extremely vascular lesions (12). As previously indicated, the classic chondrosarcoma usually arises at the skull base, although it has also been reported to occur in the

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is too early to draw any conclusion about the effectiveness of brachytherapy in the treatment of myxoid chondrosarcoma, but other therapeutic options are limited and our experience with this first case has been satisfactory. Received, October 29, 1991. Accepted, January 23, 1992. Reprint requests: Michael Salcman, M.D., 7801 York Road, Suite 102, Towson, MD 21204. REFERENCES: (1-39) 1.

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intermediate malignancy but is so uncommon intracranially that no definitive statements can be made about average survival. Although the first intracranial example was described as early as 1899 by Mott (21), only 6 of the 50 cartilaginous sarcomas reported by Hassounah et al. (13) were myxoid chondrosarcomas. A myxochondrosarcoma of the 4th ventricle has been described (32). The tumor was thought to arise from the stroma of the choroid plexus and demonstrated a mixed picture of osteoid formation, bone, calcification, cartilage, and fibroblastic areas. A chondromyxoma of the middle cranial fossa extending into the posterior fossa that eroded the petrous bone (25) and a primary meningeal myxochondrosarcoma arising at the skull base from dura mater near the foramen magnum (34) also have been reported. In contrast to mesenchymal chondrosarcoma, myxoid chondrosarcoma is glycogen-positive and negative for collagen fibrils by electron microscopy. The radiographic appearance resembles that of classic chondrosarcoma. The tumor is usually avascular by angiography and only nominally enhancing by CT scan. Similarly, modest enhancement by MRI scan was observed in our case. The major differential diagnosis is meningioma, because of the hyperostosis or lysis seen on plain xray as well as the appearance of these tumors by CT and MRI scan. As with other types of cartilaginous tumors, the extent of surgical resection is the key to therapy. No adjuvant therapy for myxoid chondrosarcoma has been reported, although a second operation may be of value in the treatment of recurrent tumors. Interstitial implantation of high activity 125I sources (brachytherapy) in recurrent skull base tumors has been used in an effort to gain local control of tumor growth (6,11,17). Gutin et al. (11) treated 5 patients with chordomas of the skull base after previous fractionated radiotherapy with permanent implantation of 125I sources, using doses from 5000 to 15,000 cGy. One patient died 1 month after implantation from rapid tumor regrowth and brain stem compression, 2 patients died 4 and 19 months after brachytherapy without evidence of tumor regrowth, and 2 patients had tumor recurrence at 19 and 28 months. Kumar et al. (17) implanted two highactivity 125I seeds transnasally into a recurrent clival chordoma with complete resolution of tumor and no evidence of recurrence 18 months after treatment. We found no example of chondrosarcoma or myxoid chondrosarcoma treated with brachytherapy and decided to implant multiple permanent low-dose 125 I seeds after the second operation, giving a total dose of 15,000 cGy, based on our previous experience with this modality in the treatment of malignant meningiomas (29). Brachytherapy has a high radiobiological effectiveness compared with the conventional high-energy fractionated x-rays used for external beam therapy. During brachytherapy, a large fraction of tumor cells are exposed to radiation during the most radiosensitive segments of their cell cycles (mitosis and G1/S boundary), and a maximum therapeutic dose can be given to the tumor with relative sparing of surrounding normal tissues (6,17). It




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Scheithauer BW, Rubinstein LJ: Meningeal mesenchymal chondrosarcoma: Report of eight cases with review of literature. Cancer 42:2744-2752, 1978. Scott RM, Dickersin GR, Wolpert SM, Twitchell T: Myxochondrosarcoma of the fourth ventricle: Case report, J Neurosurg 44:386-389, 1976. Sen CN, Sekhar LN, Schramm VL, Janecka IP: Chordoma and chondrosarcoma of the cranial base: An 8-year experience. Neurosurgery 25:931-941, 1989. Smith T, Davidson R: Primary meningeal myxochondrosarcoma presenting as a cerebellar mass: Case report. Neurosurgery 8:577-581, 1981. Suit HD, Goitein M, Munzenrider J, Verhey L, Davis KR, Koehler A, Linggood R, Ojemann R: Definitive radiation therapy for chordoma and chondrosarcoma of base of skull and cervical spine. J Neurosurg 56:377-385, 1982. Steiner GC, Mirra JM, Bullough PC: Mesenchymal chondrosarcoma: A study of the ultrastructure. Cancer 32:926-939, 1973. Waga S, Matsushima M, Ando K, Morii S: Intracranial chondrosarcoma with extracranial metastases: Case report. J Neurosurg 36:790794, 1972. Wu WQ, Lapi A: Primary non-skeletal intracranial cartilaginous neoplasms: Report of a chondroma and a mesenchymal chondrosarcoma. J Neurol Neurosurg Psychiatry 33:469-475, 1970. Zucker DK, Horoupian DS: Dural mesenchymal chondrosarcoma: Case report. J Neurosurg 48:829-833, l978..

COMMENT The authors describe a unique case of a myxoid chondrosarcoma of the falx and give a detailed description of the clinical, radiological, and pathological findings. The discussion is scholarly and delineates the pathological, biological, and natural history of the various types of chondrosarcomas. I strongly concur with the value of this differentiation, particularly for diagnostic and therapeutic considerations. This histological subtype was a clear prognostic factor in our review of the literature (1). Of particular interest is the long-term effectiveness of the brachytherapy used in this patient. Ossama Al-Mefty Maywood, Illinois REFERENCES: (1) 1.

Hassounah M, Al-Mefty O, Akhtar M, Jinkins JR, Fox JL: Primary cranial and intracranial chondrosarcoma: A survey. Acta Neurochir (Wien) 78:123-132, 1985.

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JR, Fox JL: Primary cranial chondrosarcoma: A survey. Acta Neurochir (Wien) 78:123-132, 1985. Heros RC, Martinez AJ, Ahn HS: Intracranial mesenchymal chondrosarcoma. Surg Neurol 14:311-317, 1980. Kondziolka D, Lunsford LD, Flickinger JC: The role of radiosurgery in the management of chordoma and chondrosarcoma of the cranial base. Neurosurgery 29:38- 46, 1991. Kubota T, Hayaski M, Yamamoto S: Primary intracranial mesenchymal chondrosarcoma: Case report with review of the literature. Neurosurgery 10:105-110, 1982. Kumar PP, Good RR, Leibrock LG, Mawk JR, Yonkers AJ, Ogren FP: High activity iodine 125 endocurietherapy for recurrent skull base tumors. Cancer 61:1518-1527, 1988. Lewis RJ, Ketcham AS: Maffucci's syndrome: Functional and neoplastic significance. J Bone Joint Surg 55:1465-1479, 1973. Lichtenstein L, Bernstein D: Unusual benign and malignant chondroid tumor of bone: A survey of some mesenchymal cartilage tumors and malignant chondroblastic tumors, including a few multicentric ones, as well as many atypical benign chondroblastomas and chondromyxoid fibromas. Cancer 12:11421157, 1959. Minagi H, Newton, TH: Cartilaginous tumors of the base of the skull. Am J Roentgenol 105:1197-1208, 1962. Mott FW: Chondro-sarcoma springing from the sella turcica. Arch Neurol Psychiatry 1:423-433, 1899. Nagata S, Sawada K, Kitamura K: Chondrosarcoma arising from the falx cerebri. Surg Neurol 25:505-509, l986.. Nakashima Y, Unni KK, Shives TC, Swee RG, Dahlin DC: Mesenchymal chondrosarcoma of bone and soft tissue: A review of 111 cases. Cancer 57:2444-2453, l986.. Raskind R, Grant S: Primary mesenchymal chondrosarcoma of the cerebrum. Report of a case. J Neurosurg 24:676-678, 1966. Richardson RR, Deshpande VS, Thelmo WL, Rothballer A: Chondromyxoma of the middle cranial fossa: Case report. Neurosurgery 8:707711, 1981. Rollo JL, Green WR, Kahn LB: Primary meningeal mesenchymal chondrosarcoma. Arch Pathol Lab Med 103:239-243, l979.. Roy S, Chopra P, Prakash BB, Tandon PN: Chondrosarcoma of the meninges. Acta Neuropathol (Berl) 22:272-274, 1972. Rubinstein LJ: Tumors of the Nervous System. Washington, DC, Armed Forces Institute of Pathology, 1972, pp 192-193. Salcman M: Malignant meningiomas, in AlMefty O (ed): Meningiomas. New York, Raven Press, 1991, pp 75-85. Sarwar M, Swischuk LE, Schechter MM: Intracranial chondromas. Am J Roentgenol 127:973-977, 1976.

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Figure 2. Light micrograph. Tumor typically consists of short strands and cords of small anaplastic tumor cells. The cytoplasm is a small eosinophilic rim and is often markedly vacuolated. No distinct lobulation is noted. Foci of chondroid differentiation are not present (hematoxylin and eosin stain, ×770).

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Figure 1. A, sagittal T1-weighted MRI scan demonstrates a hypointense, well-demarcated lesion in the parafalcine region, with homogeneously high intensity on axial T2-weighted images (B).

Figure 4. Axial T1-weighted MRI scan with intravenous administration of gadopentetate dimeglumine at recurrence demonstrates a wellcircumscribed mass with homogeneous enhancement in the left parafalcine area.

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Figure 3. Electron micrograph showing tumor cell. The nucleus is small and euchromatic with deep and irregular indentations. This typical cell has a slightly scalloped surface and occasional fine filopodia. There is also RER of small caliber, moderate amounts of Golgi complex, and lipid droplets. Filamentous accumulations are seen focally. The extracellular material is granuloflocular without particular structure. No RER-mitochondrial complex or desmosomes, as seen in chondromas, were observed. The appearance is consistent with a neoplastic chondrocyte or chondroblast (×10,000).

Figure 6. T1-weighted coronal image with gadopentetate dimeglumine, 4 months after the second operation, shows a small area of contrast enhancement in the left cingulate region without apparent tumor recurrence.

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Figure 5. T1-weighted sagittal image after second operation and implant of 125I seeds. Multiple seeds are visualized as signal voids in the parafalcine region. High signal intensity indicates postoperative bleeding.

Extraskeletal myxoid chondrosarcoma of the falx.

Intracranial cartilaginous tumors are unusual lesions, of which myxoid chondrosarcoma is the rarest. We describe this tumor arising from the falx in a...
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