DISCUSSION
Primary oligodendrogliomas of the spinal cord are rare and represent 2% of all tumors arising from the spinal cord and film terminal and 1.59% of all oligodendrogliomas
2,3). Since the first report of a primary spinal oligodendroglioma by Kernohan et al.
8) in 1931, including this case report only 56 cases of primary spinal cord oligodendrogliomas have been reported in the literature
2,3,4,6,8,9,13).
Primary oligodendrogliomas occur in both children and adults, with a mean age of 28.4 years old according to the literature review by Fountas et al.
4). It is widely accepted that intracranial oligodendrogliomas are more common among males; however, the existent literature shows that there is no significant gender trend with regard to spinal oligodendrogliomas
1,4). By the literature, most commonly presenting symptoms are spinal pain and sensory deficit, followed by motor deficit and voiding problems, which depend on the anatomic location of the tumor. Occasionally, several case reports have revealed increased intracranial hypertension due to diffuse oligodendrogliomatosis
6). The most common anatomic locations of spinal oligodendrogliomas are the thoracic level, followed by the cervical, thoracocervical junction, lumbar and thoracolumbar levels
4,7).
MRI is the diagnostic method of choice. Primary spinal oligodendrogliomas usually appear as heterogeneous hypoor iso-signal intense lesions on T1WI and as hyper-signal intense lesions on T2WI
14). The vast majority of spinal oligodendrogliomas demonstrate mild to moderate heterogeneous spotty enhancement on postgadolinium images
14). Cystic components or cystic necrotic areas may be observable, particularly in cases of high-grade spinal oligodendrogliomas
5,7,14). In addition to MRI, plain X-rays and CT scans can be helpful for evaluating tumor-associated skeletal deformities and instances of calcification. The presence of calcification in spinal cord oligodendrogliomas has been estimated to range from 28% to 40%
1). In this case, the initial MRI showed typical iso-intense lesions on T1WI and hyper-intense lesions on T2WI, with focal heterogeneous weak enhancement. The margin of the tumor was relatively well demarcated by MRI; however, the tumor was difficult to distinguish from the normal spinal cord intraoperatively. A CT scan showed calcification in the tumor. Postoperative five-year follow-up MRI revealed an increase in lesions size and extent of the residual tumors with cystic changes and focal enhancement, suggesting the possibility of a highgrade component as well as changes related to the radiotherapy.
The classic microscopic appearance of oligodendrogliomas is an infiltrating glial neoplasm composed of monotonous clear cells with perinuclear halos, called a "fried egg" appearance, embedded in a scaffolding of "chicken wire" vessels
1,4). According to immunohistochemical analyses, spinal oligodendrogliomas generally show no expression to GFAP but occasionally reveal focal immunoreactivity due to the presence of scattered astrocytes in the tumor bed or the presence of minigemistocytes
1,4,7). In adult intracranial oligodendrogliomas, approximately 80% contain characteristic chromosome 1p36 and 19q13 co-deletion, which appears to correlate with chemosensitivity
7). In this case, immunohistochemistry on GFAP was focal-positive, which are compatible with minigemistocytic oligodendrocytes. Interestingly, there was no chromosome 1p/19q co-deletion according to FISH in this case. This is one of the reasons that radiotherapy was preferred over chemotherapy as an adjuvant therapy for this patient. Another molecular pathologic examination of MGMT gene-promoter methylation by PCR showed a positive result. According to a literature review done by the authors, this is the first case report of the primary spinal oligodendroglioma with MGMT gene-promoter methylation and without 1p/19q co-deletion. More case reports and long-term follow up are necessary to understand the clinical significance of these results.
There is no uniform treatment guideline, but of key importance during treatment is maximal surgical resection of the tumor
3,7). However, despite the use of intraoperative electrophysiological monitoring and microsurgical techniques, surgical removal of spinal cord oligodendrogliomas is challenging in many cases due to the infiltrative characteristic of the tumors and high-grade malignancy in a large proportion of reported cases
1,3,4,6,10,12). Interestingly, among the cases reported in the literature, gross total resection was achieved in only 8 out of 56 cases
4,7). Although this patient underwent surgery with intraoperative electrophysiological monitoring and microdissection techniques, a poorly demarcated tumor margin prevented radical resection of the tumor.
The effectiveness of adjuvant radiotherapy is still controversial
4). Although Fortuna et al.
3) in 1980 reported that radiotherapy after an operation appeared to prolong survival; their study was limited in its evaluation given its analysis of only eleven cases prior to 1980. On the other hand, radiotherapy has been linked to complications such as post-radiation myelopathy and radiation-induced vertebral column deformities, especially among pediatric patients
3,12). Therefore, the decision to use postoperative radiotherapy should be made very carefully, considering the age, extent of resection, grade and histologic characteristics of the tumor, as well as the genetic characteristics of the tumor
7). In the present case, conditions such as a young age, a large residual WHO grade II oligodendroglioma and negative results for 1p/19q co-deletion were good indications for postoperative adjuvant radiotherapy. After radiotherapy, there was no evidence of the radiation induced complications described above until the fifth year postoperative follow-up examination.
Postoperative chemotherapy has been employed in limited cases of partially resected spinal oligodendrogliomas
1,5,6,10). McLendon et al.
1) and Ramirez et al.
10) reported spinal oligodendroglioma patients treated with procarbazine, lomustine, and vincristine. Guppy et al.
6) reported a good response after administering temozolomide with concurrent local radiotherapy of 45Gy for a spinal oligodendroglioma with co-deletion of 1p and 19q. However, these data are very limited, and chemotherapy has been considered as the only adjuvant treatment option for cases of partially resected high-grade oligodendrogliomas for which radiotherapy may have severe side effects
7). For the current case, there was only MGMT gene promoter methylation without chromosome 1p/19q co-deletion, which is not favorable for chemotherapy. However, given the revealed radiological progression of the tumor after postoperative radiotherapy, additional chemotherapy can be considered as a further treatment option.
The postoperative prognosis of spinal oligodendrogliomas has been reported to be less favorable than that of low-grade intramedullary astrocytomas
3). Fortuna et al.
3) reported in their review that the mean survival time was 28.6 months. In this study, we report a spinal cord oligodendroglioma patient with four years of progression-free survival, only after subtotal removal of the tumor and adjuvant radiotherapy.
Despite the radiological progression of the disease, and considering that the symptoms and performance status of the patient remained unchanged, further treatment has not been performed and the patient is on close observation with annual MRI follow ups. If the performance status of the patient is aggravated or radiological progression become evident, a second operation or adjuvant chemotherapy should be considered.