Spinal Intramedullary Glioblastoma in a Patient Previously Irradiated for Childhood Head and Neck Embryonal Rhabdomysarcoma: Case report and Review of the Literaturecase re

Radiation therapy is a well-known potential carcinogenic treatment and the association of radiation-induced intracranial-spinal tumor has been well documented since 1950. The most frequent radiation induced spinal tumors are meningiomas, followed by gliomas and sarcomas [1]. Spinal glioblastoma (GMB) represents a very rare presentation, accounting for only 1.5% of all spinal cord tumors [2], for the most part astrocytomas, followed by ependymomas [3]. An intra-medullary finding is mostly observable during the second and third decades and involves the thoracic region [4]. There are reported cases of cervical spinal GBM [5-6]. We present a case, with a systematic review of the literature, of spinal intramedullary GBM in a patient with an oncological history of head and neck embryonal rabdomyosarcoma, treated with radiotherapy and chemotherapy in 1982 and who was cured from this disease.

In September 2011, a 37-year-old man was referred to our department after recent onset of paresthesias/dysethesias on the left side of his body without motor weakness. He had history of head and neck (epypharyngeal) embryonal rabdomyosarcoma in 1982 at which time patient was successfully treated with surgery, adjuvant radiation therapy with 60Cobalt machine (total dose of 57 Gy/32 fractions; estimated dose to cervical spine and brain stem structure roughly in the range of 40 Gy) and chemotherapy (doxorubicin, cyclophosphamide and vincristine; nine cycles completed in December 1983). To investigate his symptoms at this admission, we performed brain and spinal magnetic resonance imaging (MRI) that showed an intramedullary neoplastic lesion of the cervical spinal tract (C2-C5), (Figure 1-2).

A thoracic and abdominal computer tomography scan (CT) showed no evidence of disease metastasis and clinical staging was completed with a cerebrospinal fluid analysis (CFS) that was negative for tumor cells. Biopsy of the intramedullary tumor through C2-C5 laminectomy showed it to be a GBM with small cell characteristics and a high level of cellular proliferation (Ki67:70%). Radiation treatment of the cervical lesion was planned for a total dose of 54 Gy in 27 fractions, despite the fact that the cervical spinal cord as well as medulla oblongata had already received a dose very close to the tolerable one during the previous radiation treatment.  Patient was treated during November-December 2011; unfortunately, during the third radiation treatment week, after a total dose of 32 Gy, clinical worsening was observed with respiratory distress, potentially related to the involvement of respiratory center. Patient died 2 days after the onset respiratory symptoms.

SYSTEMATIC REVIEW

A PubMed search from January 1960 to January 2013 was performed to include all relevant studies using the combination of the term radio-induced brain tumor, radiotherapy and spinal intramedullary glioma. We identified 27 studies of which 8 fulfilled our inclusion criteria and were considered in our systematic review (Table 1).

Cahan and colleagues had defined some signs to identify a radiation-induced tumor; there must be a latency time between irradiation and tumor development, tumor must arise in the irradiated area and must have a different histology than the primary and finally no immunodeficiency conditions must exist [7]. Our reported case met all of these criteria. Evidence of radiation-induced glioma in the spinal cord is only circumstantial as very few cases have been documented and including our case a total of 9 cases were reported in the literature. In 4 cases, spinal glioma were related to Hodgkin disease [8-11], in 1 case to thyroid cancer [12], one case to medulloblastoma [13], one to pulmonary tuberculosis [14], and one to radbomyosarcoma [15]. In the majority of cases radiation-induced high-grade gliomas were associated with a previous radiation treatment for Hodgkin’s lymphoma and in all patients radiation treatment was completed before 30 years of age. All patients were treated with a previous radiation dose greater than 30 Gy with a range of 30-52 Gy; only in one case radiation dose was not reported [14]. In literature, the range latency period in radiation-induced brain gliomas is 9.2 to 16 years [16] and in our case report the latency period was 29 years. Spinal GBM have a very poor prognosis and an aggressive multimodal therapy is recommended [17]. There are no standard guidelines and limited international experiences are available. An aggressive surgery is not possible due to the absence of a cleavage plan between tumor and spinal cord leading to a serious neurologic sequela in case of extensive tumor resection [3].  Radiation therapy represents the most important therapeutic option and in most cases the only therapy. Wook-Ha Kim and colleagues [18] evaluated the role of chemotherapy in this subgroup of patients. Unfortunately, small samples, and the use of different chemotherapy regimens and therapeutic modalities (concomitant or adjuvant chemotherapy) do not allow firm conclusions. In our patient, radiation therapy alone was performed and previous spinal irradiation was not considered a contraindication for radical radiation treatment because in our opinion the theoretical advantage of tumor control counteracted the probability of developing a radiation induced myelopathy.

In our opinion an aggressive treatment, represented by radical radiation therapy alone or combined with temozolomide chemotherapy may be recommended in highly selected patients; however clinical studies are needed to standardize the treatment of spinal high-grade glioma.

1. Liwnicz BH, Berger TS, Liwnicz RG, Aron BS. Radiation- associated gliomas: A report of four cases and analysis of postradiation tumours of the central nervous system. Neurosurg 1985;17:436-45.
2. Yeung YF, Wong GK, Zhu XL et al. Radiation-induced spinal glioblastoma multiforme. Acta Oncol. 2006;45(1):87-90.
3. Ciappetta P, Salvati M, Capoccia G, Artico M, Raco A, Fortuna A. Spinal glioblastomas: Report of seven cases and review of the literature. Neurosurg 1991; 28:302-6.
4. Cooper PR, Epstein F. Radical resection of intramedullary spinal cord tumor in adults. J Neurosurg 1985; 63:491–492.
5. Caroli E, Salvati M, Ferrante L. Spinal glioblastoma with brain relapse in a child: clinical considerations. Spinal Cord 2005; 43:565–567.
6. Chida K, Konno H, Sahara M, Takase S. Meningeal seeding of spinal cord glioblastoma multiforme without any signs of myelopathy. Rinsho Shinkeigaku. 1995;35(11):1235-40.
7. Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL. Sarcoma arising in irradiated bone: report of eleven cases. Cancer 1948; 82:8-34.
8. Clifton MD, Amromin GD, Perry MC, Abadir R, Watss C, Levy N. Spinal cord glioma following irradiation for Hodgkin’s disease. Cancer 1980; 45,8: 2051-2055.
9. Bazan C 3rd, New PZ, Kagan-Hallet KS. MRI of radiation induced spinal cord glioma. Neuroradiology. 1990;32(4):331-3.
10. Riffaud L, Bernard M, Lesimple T, Morandi X. Radiation-induced spinal cord glioma subsequent to treatment of Hodgkin’s disease: case report and review. J Neurooncol 2006;76:207-211.
11. Ng C, Fairhall J, Rathmalgoda C, Stening W, Smee R. Spinal cord glioblastoma multiforme induced by radiation after treatment for Hodgkin disease. Case report. J Neurosurg Spine 2007;6:364-367.
12. Marus G, Levin CV, Rutherfoord GS. Malignant glioma following radiotherapy for unrelated primary tumors. Cancer 1986;15;58(4):886-94.
13. Grabb PA, Kelly DR, Fulmer BB. Radiation-induced glioma of the spinal cord. Pediatr Neurosurg. 1996;25(4):214-9.
14. Steinbok P. Spinal cord glioma after multiple fluoroscopies during artificial pneumothorax treatment of pulmonary tuberculosis: case report. J Neurosurg 1980;52:838-841.
15. Ahn SJ, Kim IO. Spinal cord glioblastoma induced by radiation therapy of nasopharyngeal rhabdomyosarcoma with MRI findings: case report. Korean J Radiol. 2012;13(5):652-7.
16. Pettorini BL, Park YS, Caldarelli M, Massimi L, Tamburrini G, Di Rocco C. Radiation-induced brain tumours after central nervous system irradiation in childhood: a review. Childs Nerv Syst 2008;24:793-805.
17. Rovin RA, Winn R, Expression of O6-methylguanine-deoxyribose nucleic acid methyltransferase and temozolomide response in a patient with a malignant spinal cord astrocytoma. Case report. J Neurosurg Spine 2007 6:447–450.
18. Kim WH, Yoon SH, Kim CY, Kim KJ, Lee MM, Choe G et al. Temozolomide for malignant primary spinal cord glioma: an experience of six cases and a literature review. J Neurooncology 2011;101(2):247-54