Calcification in glioblastoma multiforme of the cervical spinal cord

Calcification in glioblastoma multiforme of the cervical spinal cord

Surg Neurol 1986;26:183-6 183 Calcification in Glioblastoma Multiforme of the Cervical Spinal Cord Toshihiko Kubota, M.D., Yuzaburo Kogure, M.D., Sh...

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Calcification in Glioblastoma Multiforme of the Cervical Spinal Cord Toshihiko Kubota, M.D., Yuzaburo Kogure, M.D., Shinjiro Yamamoto, M.D., Shiro Matsubara, M.D., Tetsuo Kitano, M.D., and Minoru Hayashi, M.D. Department of Neurosurgery and Neurology, School of Medicine, University of Kanazawa, Kanazawa; Department of Neurosurgery, Tsuruga City Hospital, Tsuruga; and Department of Neurosurgery, Fukui Medical School, Japan

Kubota T, Kogure Y, Yamamoto S, Matsubara S, Kitano T, Hayashi M. Calcification in glioblastoma multiforme of the cervical spinal cord. Surg Neurol 1986;26:183-6.

A patient having glioblastoma accompanied with calcification in the cervical spinal cord is presented. A calcifying lesion, detected on preoperative x-ray computed tomograms, was histologically confirmed as calcified areas in the tumor tissue. We discuss the difficulty in differentiating glioblastomas containing calcified masses from benign tumors with areas of calcification and present our hypothesis regarding the cause of calcification in the tumor tissue. KEYWORDS: Glioblastoma; Spinal cord; Tumor; Calcification; Computed tomography

Advances in magnetic resonance imaging have made it possible to diagnose spinal cord lesions definitively. On the other hand, high-resolution x-ray computed tomography continues to be valuable in the diagnosis of calcified lesions. Using x-ray computed tomography after intrathecal metrizamide injection, we are able to diagnose an intramedullary tumor associated with a calcified mass in the cervical spinal cord. In the patient presented here, we made a histologic diagnosis of glioblastoma accompanied by areas of calcification in the blood vessels. Although there are reports of extensive neuroradiologic studies [5,10], to our knowledge, ours is the first case of a malignant spinal cord glioma with calcifications detected by computed tomography. Case R e p o r t The patient was a 27-year-old Japanese woman with a 1-year history of numbness in the tips of her right foreAddress reprint requests to: Toshihiko Kubota, M.D., Department of Neurosurgery, School of Medicine, University of Kanazawa, 13- i Takara-Machi, Kanazawa 920, Japan.

© 1986 by Elsevier Science Publishing Co., Inc.

finger, middle finger, and ring finger. Approximately 5 months prior to hospitalization she experienced motor weakness of the right hand, occasional headache, nausea, and vomiting. One month before admission, she developed weakness of the right lower extremities and had difficulty in walking. On admission, the results of her general physical examination were normal. Neurological examination revealed spasticity with pathological reflexes of the right upper and right and left lower extremities. We noted hypesthesia at the level of the right C-2-C-4 segments and slight hyperesthesia below C-5 on the right side. Routine laboratory examinations yielded normal findings. The cerebrospinal fluid obtained by lumbar puncture was xanthochromic with 2100 mg/dL protein, 65 mg/dL sugar, and 17 cells per cubic millimeter (5% polymorphonuclear leucocytes, 95% lymphocytes). Plain roentgenograms of the spine and skull were normal. Metrizamide myelograms demonstrated enlargement of the spinal cord from C-5 to the upper cervical region, leading us to suspect the presence of an intramedullary lesion (Figure 1). Computed tomograms (GE 8800, General Electric Co., Milwaukee, WI), obtained 30 minutes after the myelogram, revealed an intramedullary high-density mass at the level of C-3 (Figure 2). In the anterior aspect of the spinal cord there was thinning of the contrast rim; in the posterior part it disappeared owing to enlargement of the spinal cord (Figure 2A). Therefore, we suspected an intramedullary mass associated with the calcified area. The contrast-enhanced computed tomogram showed a slightly enhanced lesion contiguous with the calcified mass. The computed tomogram of the head disclosed moderate dilatation of the ventricle. The patient underwent a laminectomy from C-1 to C-5 in July 1981. Upon opening the dura mater, we saw that the spinal canal was filled by a distorted, swollen, pinkish spinal cord. Superiorly, the mass extended to the cisterna magna, and inferiorly to C-5. There was a superficially discernible border between the neoplasm 0090-3019/86/$3.50

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Figure 1. Metrizamide myelogram, anteroposterior view, showing significant widening of the spinal cord from C-5 to the upper cervical region. B

and the adjacent normal cord parenchyma at the level of C-5. However, no cleavage plane was noted at any magnification. A soft, bloodless mass was partially resected because a frozen section of the tumor biopsy specimen disclosed it to be a highly malignant neoplasm primarily consisting of glial cells. Postoperatively, the patient remained neurologically unchanged; however, the signs of increased intracranial pressure subsided. She was given 2000 rads by a 10meV linear accelerator, but radiotherapy was halted because the signs of increased intracranial pressure reappeared. H e r clinical course gradually deteriorated and she expired 4 months after the operation. Permission for autopsy was refused. Histologically, the surgical specimen showed the peculiar features of a glioblastoma multiforme. Representative sections of the specimen, stained with hematoxylin and eosin, manifested randomly arranged polygonalshaped cells with fine cell processes. Occasional necrotic areas were present. Palisade-like cells were arranged around some necrotic areas (Figure 3A). The cell nuclei were polymorphic; some exhibited mitotic figures. There was significant endothelial proliferation in some blood

Figure 2. (A) Computed tomographic scan, obtained 30 minutes after the metrizamide myelogram, exhibits a round intramedullary high density mass at the level of C-3. Note thinning and disappearance of the contrast rim due to enlargement of the spinal cord. (B) The sagittal view of the reconstructed computed tomography scan demonstrates a high density mass at the C-3 level. The ruler is graduated in centimeters.

vessels. Some portions of tumor contained calcified areas, especially at the outer aspect of the blood vessels (Figure 3B). These vessels were usually surrounded by glial tumor cells, which, on histological examination, appeared to be of a benign character. On immunohistochemical staining, some of the tumor cells contained fibers that were positive for glial fibrillary acidic protein. Electron microscopic examination revealed that some of the neoplastic cell processes were filled with glial filaments. Discussion

There are a few reported cases of spinal cord glioblastoma [8,21]. Clinically, these neoplasms are characterized by a short clinical history, they primarily involve the cervical and cervicothoracic cord, they tend to occur

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A during infancy and childhood, and their prognosis is poor despite extensive surgical removal or attempts at radiation therapy [11,14]. Epstein and Epstein [7] succeeded in the gross total removal of benign astrocytomas; thus, the prognosis of patients with this neoplasm may improve. Similarly, advances in the diagnosis and treatment of patients with spinal cord malignant gliomas may improve their prognosis. The use of x-ray highresolution computed tomography and magnetic resonance imaging makes it possible to obtain an accurate diagnosis. Operative results can be improved by using real-time ultrasonography to determine the exact site of the tumor [3], and by the use of a Cavitron ultrasonic surgical aspirator (CUSA; Cooper Lasersonics, Santa Clara, CA) and a carbon dioxide laser under an operating microscope to facilitate the extensive excision of the tumor. Postoperative radiotherapy and chemotherapy may also contribute to the improved outcome of patients treated for spinal cord malignant gliomas. Calcified lesions are frequently encountered in spinal meningiomas [22], but are rarely seen in neurinomas [2], teratomas [17], or angiomas [4]. Some gliomas of the spinal cord contain calcified areas [6]. To our knowledge, there is only one report of calcified masses in a glioma of the spinal cord detected by computed tomography [19]; this patient had an astrocytoma. High-

Figure 3. (A) Photomicrograph of the surgical specimen demonstrating the pseudopalisading appearance of neoplastic cells around necrotic areas characteristic of glioblastoma multiforme (H & E, × 150). (B) Calcified areas (arrows) within the blood vessels of the tumor suggest it to be of a benign nature (H & E, × 140).

resolution computed tomography has facilitated the localization of calcifications in spinal cord tumors [9]. Computed tomographic study after intrathecal metrizamide injection allowed us to assess the precise structure of the lesion and is preferable to conventional myelography. We were able to identify the calcified area as an intramedullary lesion. Astrocytomas and ependymomas are relatively common cervical intramedullary tumors, whereas glioblastomas, polar spongioblastomas, oligodendrogliomas, and nonglial tumors (e.g., lipomas, teratomas, hemangioblastomas, carcinomas, and melanomas) are rare [18]. Calcified areas are usually present within gliomas that have a benign histologic appearance. Hence, in our case, it may be reasonable to assume that some parts of a benign astrocytoma manifesting calcifications gradually or abruptly changed into a glioblastoma. The mechanism underlying the formation of calcified areas within tumors of the central nervous system remains to be determined. Martin and Lemmen [20] classified patients with calcified intracranial neoplasms into

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four main categories on the basis of histological patterns: (1) calcifications within blood vessel walls in which small globules or calcospherites initially emerge within the adventitia or media of the small vessels, the endothelium of capillaries, or the media of large vessels; (2) calcium deposits in necrotic areas adjacent to blood vessels; (3) calcium salts in an area of old hemorrhage or necrosis; and (4) (a) calcific globules within tumor cells, (b) calcific changes within the stroma of the tumor or its capsule, or (c) calcific changes in the tumor periphery not related to types (a) or (b). These workers stated that pattern 1 is most frequently encountered. Our patient demonstrated areas of calcification in the adventitia of blood vessels within the tumor. Ultrastructural studies of various tumors have suggested that areas of calcification originate from mitochondria and matrix vesicles [1]. In pineal germinomas [ 1] and pituitary adenomas [ 12], calcium deposits were identified within mitochondria and in meningiomas; psammoma bodies in matrix vesicles contained hydroxyapatite precipitates [ 15]. Kim [13], who examined human sclerotic aorta and aortic valve, reported that their calcifications were shown as apatite depositions in matrix vesicles and in thick-wall-invested bodies larger than matrix vesicles. We previously reported [16] that in meningioma, not only the matrix vesicles but also the bodies invested in the thick wall (matrix giant bodies, measuring up to 3 /.~m in diameter) were the original sites of calcification in the adventitia of blood vessels. Based on our present and previous findings we suggest that calcifications in the blood vessels of spinal cord gliomas may derive from matrix vesicles or matrix giant bodies, and that they may be ascribable to degenerated cells in the blood vessel walls.

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5. Dorwart RH, LaMasters DL, Watanabe TJ. Tumors. In: Newton TH, Potts DG, eds. Computed tomography of the spinal cord. Modern neuroradiology. San Anselmo, CA: Clavadel Press, 1983:115-47. 6. Epstein F, Epstein N. Surgical management of holocord intramedullary spinal cord astrocytomas in children. Report of three cases. J Neurosurg 1981;54:829-32. 7. Epstein F, Epstein N. Surgical treatment of spinal cord astrocytomas of childhood. A series of 19 patients. J Neurosurg 1982 ;57: 685-9. 8. Fortuna A, Giuffr6 R. Intramedullary glioblastomas. Neurochirurgia 1971;14:14-23. 9. Garfinkle W, Yudd AP. Calcified intraspinal meningioma detected by computed tomography. Comput Radiol 1982;6:305-7. 10. Green BA, Diaz RD, Post MJD. The diagnosis of spinal column and spinal cord tumors with emphasis on the value of computed tomography. In: Post MJD, ed. Computed tomography of the spine. Baltimore: Waverly Press, 1984:659-703. 11. Guidetti B, Mercuri S, Vagnozzi R. Long-term results of the surgical treatment of 129 intramedullary spinal gliomas. J Neurosurg 1981;54:323-30. 12. Ilse BG, Ryan N, Kovacs K, Ilse D. Calcium deposition in human pituitary adenomas studied by histology, electron microscopy, electron diffraction and X-ray spectrometry. Exp Pathol 1980;18:377-81. 13. Kim KM. Calcification of matrix vesicles in human aortic valve and aortic media. Fed Proc 1976;35:156-62. 14. Kopelson G, Linggood RM. Intramedullary spinal cord astrocytoma versus glioblastoma. The prognostic importance of histologic grade. Cancer 1982;50:732-5. 15. Kubota T, Hirano A, Yamamoto S, Kajikawa K. The fine structure of psammoma bodies in meningocytic whorls. J Neuropathol Exp Neurol 1984;43:37-44. 16. Kubota T, Hirano A, Sato K, Yamamoto S. Fine structure of psammoma bodies at the outer aspect of blood vessels in meningioma. Acta Neuropathol 1985;66:163-6. 17. Lemmen LJ, Wilson CM. Intramedullary malignant teratoma of the spinal cord. Arch Neurol Psychiatry 1951;66:61-8. 18. Long DM. Cervical cord tumors. In: Bailey RW, ed. The cervical spine. Philadelphia: Lippincott, 1983;323-35. 19. Maehara T. Computed tomography of spine and spinal cord. No Shinkei Geka 1981;9:993-1006. 20. Martin F, Lemmen LJ. Calcification in intracranial neoplasms. Am J Pathol 1952;28:1107-31. 21. Mortara R, Parker JC, Brooks WH. Glioblastoma multiforme of the spinal cord. Surg Neurol 1974;2:115-9. 22. Pear BL, Boyd HR. Roentgenographically visible calcifications in spinal meningioma. Am J Roentgenol Radium Ther Nucl Med 1974;120:32-45.