Pontine glioma with osteoblastic skeletal metastases in a child

ELSEVIER

PONTINE SKELETAL

GLIOMA WITH METASTASES

OSTEOBLASTIC IN A CHILD

Youichi Yanagawa, M.D., Takahito Miyazawa, M.D., Shoichiro Ishihara, M.D., Hiroshi Takiguchi, M.D., Katsuji Shima, M.D., Shintaro Terahata, M.D.,* Seiichi Tamai, M.D.,* and Hiroo Chigasaki, M.D. Department of Neurosurgery and Laboratory Medicine,* National Defense Medical College, Saitama, Japan

Yanagawa Y, Miyazawa T, lshihara S, Takiguchi H, Shima K, Terahata S,Tamai S,ChigasakiH. Pontine glioma with osteoblastic skeletal metastases in a child. Surg Neural 1996;46:481-4.

ment of gliomas [5,6]. We report here a rare case of pontine glioma with osteoblastic skeletal metastases.

BACKGROUND

The development of systemic metastases from primary intracranial gliomas is rare. We report here a rare case of pontine glioma with osteoblastic skeletal metastases. CASE

This 12-year-old boy presented with a 4-month history of hoarseness, dysphagia, and a progressively ataxic gait. Cranial computed tomography (CT) and magnetic resonance imaging (MRl) revealed a brain stem tumor that was diagnosed as a low grade glioma by stereotactic biopsy. Twelve months later following chemotherapy and radiotherapy, neurologic examination and neuroradiologic studies disclosed a recurrence of the pontine glioma. Skeletal roentgenograms revealed widespread osteoblastic metastases in the skull, vertebra1 bodies, pelvis, and long bones. A specimen from the iliac bone demonstrated cells that were immunoreactive glial fibrillary acidic protein (GFAP). DISCUSSION

The mechanism of how glioma cells determine their bio logic behavior at bony metastatic sites is not known. Infratentorial gliomas, which occur frequently in young patients and demonstrate active bony metabolism, may stimulate osteoblastic cells, and induce osteoblastic changes. 0 1996 by Elsevier Science Inc. KEY WORDS

Pontine glioma, osteoblastic metastases, exh-acranial metastases, GFAP, child.

I

n general, the development of systemic metastases from primary intracranial gliomas is rare. Re-

cently, however, extracranial metastases of gliomas have increased in frequency due to longer survival of patients as a result of advancements in the treatAddress reprint requests to: Takahito Miyazawa, M.D., Department of Neurosurgery, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359 Japan. Received September 20, 1995; accepted February 12, 1996. 0 1996 by Elsevler Science Inc. 655 Avenue of the Americas, New York,

NY 10010

CASEPRESENTATION In March 1992, a 12-yearold boy presented with a 4-month history of hoarseness, dysphagia, and a progressively ataxic gait. Crania1 computed tomography (CT) revealed the brain stem hypertrophy without contrast enhancement. Magnetic resonance imaging @VU) disclosed a T,-low and T,-high intensity signal mass at the brain stem without enhancement with Gd-DTPA (Figure 1, left). The cranial, chest, and abdominal radiographs did not reveal any osteoblastic or osteolytic changes at that time. A sterotactic biopsy was performed in April 1992. The pathologic diagnosis based on the analysis of a biopsy of the specimen was low grade fibrillary astrocytoma (Pigure 2A). The patient was treated by irradiation with 5,000 cGy in 200 cGy daily fractions, the intrave nous administration of 250 x 10 4 LU. Interferon three times a week and 1-(4-amine-2-methyLSpyrimidiny1) methyl-3-(2chloroethyl)-Snitrosourea hydrochloride (ACNU) once every 4 weeks (first dose: 100 mg, second dose: 50 mg) over an 8week period from AprilJune 1992. Following treatment, the patient’s symp toms resolved, and MRl revealed a decrease in tumor size (Figure 1, center). He subsequently received intravenous administrations of 80 mg of ACNU every 6-8 weeks as an outpatient. In February 1993, the patient complained of nausea and headaches, and was readmitted in March 1993. On physical examination, he demonstrated a conjugate gaze disturbance to the right, a right facial paresis, dysphagia, and a left hemiparesis. MRl demonstrated the recurrence of the tumor with an irregular ring enhancing effect concomitant with hy0090-3019/96/$15.00 PI1 SO0903019(96)00223-6

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magnetic resonance image following q1992,theT,-weighted intravenous administration of Cd-DTPA. In April MRI revealed diffuse brain stem swelling with various low intensity regions prior to biopsy and medical treatment (/ett>. In June 1992, the tumor had decreased in size and become iso-intense following treatment (center). In March 1993, MRI revealed enhanced recurrent tumor with exophytic growth following the administration of Gd-DTPA (right). drocephalus (Figure 1, right). Skeletal roentgenograms (Figure 3) revealed widespread sclerotic metastases in the skull, vertebral bodies, pelvis, and

long bones that were also demonstrated by the positive uptake of 67 Ga on a scintigram. In April 1993, partial resection of the tumor was performed via a transpetrosal-transtentorial ap preach. Decompression of the posterior fossa, placement of a ventriculo-peritoneal shunt, and biopsy of the iliac bone all were performed concurrently. The pathologic diagnosis of a tumor specimen was anaplastic astrocytoma (Figure 2B). Tumor cells of the iliac bone were immunoreactive stained for glial fibrillary acidic protein (GFAP) (Figure 2C). Despite aggressive therapy, the patient followed a deteriorating course and died on January 13, 1994. An autopsy ruled out the possibility of another primary site of the tumor.

DISCUSSION Smith et al [13], reported that 35 (0.44%) astrocytomas, including 23 glioblastomas, of 8000 neuroectodermal central nervous system (CNS) tumors demonstrated extraneural spread. According to Nakamura [9], 100 (3.3%) of 3038 CNS tumors, including meninges derived tumors, exhibited systemic

(A) Specimen from first operation in April 1992. The micrograph reveals a low grade fibrillary astrocytoma (Hematoxylin and Eosin 400). (B) Specimen from the second operation in April 1993. The micrograph demonstrates a highly cellular glioma with pleomorphism and hyperchromatism (H&E 400). (C) Specimen obtained by biopsy of the iliac crest revealing cells immunore active for GFAP 400).

x

X

(X

Pontine Glioma with Osteoblastic Metastases

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morphology of the CNS tumor and of the distant metastases must have been identical with due allowance for differences in degree of anaplasia. In this case, radiologic studies and autopsy did not reveal another primary site. Also, a biopsy specimen from an iliac bone was immunoreactive positive for GFAP. Consequently, we diagnosed this patient with bony metastases from a pontine glioma

1151.

Abdominal radiograph showing widespread osteoQ blastic metastases involving the vertebral bodies, pelvis, sacrum, and femurs.

metastases. Among them, medulloblastomas, glioblastomas, and malignant meningiomas had the highest incidences. These two reports document that higher incidences of malignant tumors result in higher incidences of metastases. Extracranial metastases, even from low grade gliomas, have also been reported [4,6]. Potential mechanisms of extracranial spread of brain tumors include direct vascular invasion followed by distant hematogenously distributed metastases. Although extracranial metastases of gliomas are usually triggered by surgical interventions, rare spontaneous metastases have also been reported [2]. In 1955, Weiss [ 141 defined the following criteria for a metastasizing CNS glioma: (1) the presence of a single histologically characteristic tumor of the CNS must have been proved; (2) the clinical history must indicate that initial symptoms were due to this tumor; (3) a complete autopsy must have been performed and reported in sufficient detail to rule out the possibility of any other primary site; and (4) the

In 1980, Pasquier et al [lo] analyzed the characteristics of extracranial metastases of 72 gliomas. The average patient age was 35.8 years (range: 3.5-70 years) and male-to-female sex ratio was 46: 26. Sixty-seven of the gliomas in their study were supratentorial, and the distribution of metastases included 43 (59.7%) to the lungs or pleura, 37 (51.4%) to lymph nodes, 22 (30.5%) to bone, and 16 (22.2%) to the liver. According to Longee et al [6] who analyzed cases of bony metastases of astrocytederived tumors, the most common site of metastases was the vertebrae (73%), followed by the ribs, pelvis, and appendicular skeleton. There have been no previous reports of which the theme was radiologic characteristics of bony metastases originating from glioma. In addition, since the case reports have not described the characteristics of bony metastases in detail, the exact ratio between osteoblastic and osteolytic metastases could not be clarified. There is a report of one patient who had abnormal tracer accumulation on a bone scintigram, without abnormalities on plain radiographs; the diagnosis in this case proved to be bony metastases of a glioma on autopsy [5]. Eight cases of glioma osteoblastic metastases are summarized in Table 1 [ 1,2,4,6,9,11]. The average age of these patients was 21.2 years (range: 9-56 years). The interval from diagnosis to metastases ranged from O-70 months (average: 21.7 months). Survival from the apparent onset of symptoms ranged from 4-97 months (average: 20.5 months). Four cases (50%) were infratentorial in origin. The reason why osteoblastic metastases occur predominantly in cases of infratentorial glioma is unknown. The Batson’s plexus may play a role in causing drop metastases following the vertebral invasion. Osteolytic vertebral metastases from gliomas do not occur predominantly in cases of infratentorial tumors [9]. The reason for this difference may be because infratentorial gliomas, which occur frequently in young patients and demonstrate active bony metabolism, may stimulate osteoblastic cells, and induce osteoblastic changes [5,7,12]. At present, however, the mechanism of how glioma cells determine their biologic behavior at bony metastatic sites requires further clarification. Further studies are also

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Clinical Features of Osteoblastic Metastases of Gliomas LOCATION

METASTATIC Sms

Malignant astrocytoma Malignant astrocytoma Astrocytoma Oligodendroglioma Glioblastoma

Rt. frontal lobe Brain stem Lt. parietal lobe Rt. frontal lobe Brain stem

F M

Astrocytoma Malignant astrocytoma

M

Malignant astrocytoma

Brain stem Rt. cerebral hemisphere Brain stem

Vertebrae, clavicle, ribs Pelvis, sacrum, vertebrae, femur Vertebrae, pelvis Vertebrae, pelvis, rib Vertebrae, pelvis, facial bones, femur, tibia Vertebrae, pelvis, femur Vertebrae, pelvis, rib

CASE

1. 2. 3. 4. 5.

Schatzi et al, 1977 Choi et al, 1981 Kingston et al, 1986 Nakamura et al, 1985 Gamis et al. 1989

56 23 13 32 11

M M M F F

6. 7.

Longee et al, 1991 Longee et al, 1991

9 13

8.

Present case

12

M: male, F: female,

required

rt.: right,

to establish

cally metastasizing

PATHOLOGIC DIAGNOSIS

AGE SEX

No.

Vertebrae, pelvis, skull, long bone

It: left.

effective therapy

for systemi-

gliomas [8,9].

REFERENCES 1. Choi B, Holt J, Mcdonald J. Occult malignant astrocytoma of pons with extracranial metastasis to bone prior to craniotomy. Acta Neuropathol (Berl) 1981; 54:269-73. 2. Gamis AS, Egelhoff J, Rosolon C, Young J, Woods GM, Newman R, Freeman AI. Diffuse bony metastases at presentation in a child with glioblastoma multiforme. Cancer 1990;66:180-84. 3. Hornsby V. Bony metastases from malignant intracranial astrocytoma. Neuroradiology 1985;27:426-29. 4. Kingston J, Plowman P, Smith B, Garvan N. Differentiated astrocytoma with osteoblastic skeletal metastases in a child. Child Nerv Syst 1986;2:219-21. 5. Kosuda S, Suzuki K, Nakamura 0, Nakanura H, Shidara N, Matsutani M, Kamata N. Usefulness of bone scintigraphy in postoperative patients with medulloblastoma. J Medical Imagings 1992;12:338-343. 6. Longee DC, Friedman HS, Phillips PC, Burger PC, Oakes WJ, Heffez D, Wharam M, Strauss L, Fuller GN, Schold SC. Osteoblastic metastasis from astrocytomas: a report of two cases. Medical and Pediatric Oncology 1991;19:318-24. 7. Lorusso P, Tapazoglou E, Zarbo R, Cullis P, Alasrrar M. Intracranial astrocytoma with diffuse bone marrow metastasis: a case report and review of the literature. J Neuro-Oncology 1988;6:53-59. 8. Martin 0. Combination chemotherapy for extracranial metastases of a primary malignant cerebral neoplasm. Cancer Treatment Rep 1979;63(8):1417-18. 9. Nakamura K. Metastasizing brain tumor. Japanese J Cancer Clinics 1986;32(3):281-86. 10. Pasquier B, Pasquir D, N’Golet A, Panh MH, Couderc P. Extraneural metastases of astrocytoma and glioblastomas. Cancer 1980;45:112-25. 11. Schatzi S, McIlmoyle G, Lewis S. Diffuse osteoblastic metastasis from an intracranial glioma. Am J Roentgenol 128:321-23, 1977. 12. Silverman FN. In: Silverman FN, ed. Caffey’s pediatric X-ray diagnosis, 8th ed, Chicago: Year Book Medical Publishers, 1985:882.

13. Smith DR, Hardman JN, Earle KM. Metastasizing neuroectodermal tumors of the central nervous system. J Neurosurg 1969;31:50-58. 14. Weiss L. Metastasizing ependymoma of the cauda equina. Cancer, N.Y., 8:161-71, 1955. 15. Yung WKA, Tepper SJ, Young DF. Diffuse bone marrow metastase by glioblastoma: premortem diagnosis by peroxidaseantiperoxidase staining for glial fibrillary acid protein. Ann Neurol 1983;14:581-85.

COMMENTARY

Diffuse intrinsic stereotactic

brain stem gliomas

biopsy.

They

all

follow

do not need the

same

course. Following treatment with chemotherapy and radiotherapy, the tumor virtually disappears, only to reappear within 1 year leading to the child’s death. At postmortem, these patients had diffuse ‘leptomeningeal spread of their tumors. The authors are to be congratulated on demonstrating that not only can there be leptomeningeal metastases of this malignant tumor, but also extracerebral metastases. 1 must emphasize the uselessness of stereotactic biopsy for these diffuse tumors. The original specimen was felt to be a low-grade fibrillary astrocytoma. The reason for this is that these tumors are probably mixed, and the initial imaging rarely shows enhancement. However, in the course of time the tumor begins enhancing, and by that time the tumor is virtually completely malignant. In North America, the pediatric neurosurgical community has concluded that stereotactic biopsy has no role to play in diffuse intrinsic brain stem gliomas. Harold

J. HofFman,

M.D., F.R.C.S.C.

Toronto, Ontario, Canada