INTRODUCTION
The incidence of dumbbell-shaped tumors accounts for 18% of all spinal cord tumors, and among these, 44% occur most commonly in the cervical spine [
1]. Spinal schwannoma is the most frequent primary spinal cord tumor of which dumbbell-shaped tumors account for 6%–23% [
2,
3]. For spinal dumbbell-shaped schwannomas (DS), the most appropriate surgical approach is always debatable because of the complexity of the proportion of extraforaminal components. The surgical approaches for spinal DS are roughly classified into 3 groups: anterior/lateral one-way approach, posterior one-way approach, and combined anterior/lateral and posterior approaches.
En-bloc gross total resection (GTR) is the most desirable procedure and should be performed when possible because the recurrence rate of spinal DS after GTR is low, ranging from 0% [
4-
6] to 3.2% [
7]. However, some procedures for GTR could be extensive and invasive, with high complication rates [
2,
8], and the anatomical location of the vertebral artery (VA) and spinal nerve roots can make achieving GTR safely difficult [
4,
9-
11]. Given these adverse circumstances for GTR, incomplete resection (IR) occasionally needs to be performed and the intraforaminal and extraforaminal components are involuntarily left after posterior one-way surgery. Accordingly, the postoperative behavior of remnant tumors after IR, rather than the recurrence rate of tumors after GTR, should be highlighted, and several studies have investigated it [
4,
7,
12-
15]. However, the reported growth rates of remnant tumors ranged widely from 16.7% [
15] to 60% [
12,
13], and most studies have failed to propose clinical implications to predict remnant tumor growth. Thus, this study investigated remnant tumor growth after IR of cervical DS and identified its predictive factors.
DISCUSSION
In this study, we examined the growth of remnant tumors after IR of cervical DS and investigated its predictive factors. Our findings revealed that the anatomical location of the remnant tumor margin was the most significant predictor of remnant tumor growth. This result suggests that remnant tumors with its surgical margin distally away from the entrance of the intervertebral foramen were less likely to grow into the spinal canal even when the extraforaminal components are involuntarily left after a posterior one-way surgery.
Reportedly, the occurrence rate of remnant tumor growth after IR ranged from 16.7% to 60% [
4,
12-
15]. Ryu recently performed quantitative analyses of remnant tumor sizes after IR of cervical DS in 31 patients [
7]. Seven (Eden type II or III [
17]) of the 31 cases (22.6%) showed remnant tumor growth during the mean follow-up period of 16 months, and among the 7 cases, 2 underwent reoperations because of the newly developed symptoms caused by the growth. In this series, no significant differences in age, sex, tumor location by Eden classification, and preoperative and postoperative tumor sizes were found between patients with and without remnant tumor growth. This study revealed that frequent postoperative MRI follow-up is important but it could not indicate the predictive factors for the growth of remnant tumors, which could help us plan the surgical and postoperative strategies. To summarize the results of studies in addition to Ryu’s study, detailed information, including the spinal segment of the tumor (cervical, thoracic, or lumbar), surgical approaches (posterior, anterior, or combined), remnant tumor margin (intradurally, extraforaminally, or interosseously), directions of remnant tumor growth (into the spinal canal or extraforaminally), and MIB-1 index, was not fully provided. Therefore, knowing the long-term behavior of remnant tumors after IR of cervical DS and the kind of factor that would have the most significant impact on the remnant tumor growth is still difficult.
In this study, 10 of the 21 patients (47.6%) showed remnant tumor growth during the mean follow-up period of 61 months. The directions of the residual tumor growth were bidirectional both extraforaminally and into the spinal canal in 8 patients and unidirectional into the spinal canal in 2 patients. Note that the growth was directed at least into the spinal canal in all patients, whereas 11 of the 21 patients (NG group, 52.4%) showed no growth during the mean follow-up period of 74 months. This obvious difference in the fate of the remnant tumors between the 2 groups prompted us to investigate the predictive factors of their growth.
As far as we investigated, the MIB-1 index is the only one factor used as a prognostic marker of remnant tumor growth after IR of spinal DS. Sohn reported that the average MIB-1 index was significantly higher in patients with remnant tumor growth (6.3%±5.6%) than in those without growth (2.0%±1.6%) [
14]. In addition, Nakamura indicated the clinical significance of the MIB-1 index and proposed that additional resection using the anterior approach should be considered when the MIB-1 index is high (> 5%) to remove the remnant tumor after IR during the initial posterior-approach operation [
4]. However, these studies only showed a descriptive indication regarding the possibility of reoperation after remnant tumor growth. Therefore, the current study performed quantitative and statistical analyses to identify the predictors of remnant tumor growth, but our findings indicate that the MIB-1 index has no association with remnant tumor growth.
Fukuda et al. [
18] reported that the thickness of the remnant tumor after IR of vestibular schwannoma (VS) using the lateral suboccipital approach, which was defined as the maximum diameter of the remnant tumor on the same side of the internal acoustic canal (IAC) with the brainstem and cerebellum, was positively related to its growth toward the brainstem and cerebellum. Another recent study reported that remnant VS locations other than IAC had greater risk of remnant VS regrowth than those in IAC [
19]. On the basis of this finding, we hypothesized that remnant tumor growth into the spinal canal could be affected by the anatomical location of the remnant tumor margin relative to the border dividing the spinal canal and intervertebral foramen. The posterolateral corner of the intervertebral disc or the vertebral body was defined as an anatomical landmark indicating the border, and accordingly, the proximal margin at the corner or within the spinal canal, compared with the distal margin in the intervertebral foramen away from the corner, was identified as a significant predictor of remnant tumor growth (OR, 56.0; 95% CI, 2.93–1,072; p=0.008). These findings suggest that the proximal margin on the verge of the spinal canal and intervertebral foramen leaves a greater chance for a remnant tumor to grow into the spinal canal. This anatomical implication could help us establish a surgical strategy preoperatively and decide the final surgical margin intraoperatively to lower the risk of remnant tumor growth. However, at the same time, we should know that posterior one-way approach to resect the intra- and extraforaminal portion of the tumor distally from the entrance of the foramen might increase the risk to injure VA behind the tumor since VA cannot be controlled posteriorly [
9]. Additionally, the remnant tumor margin on the postoperative MRI does not necessarily reflect the intraoperative surgical margin, especially when IR was performed within the capsule because the fluid or hematoma filling the cavity after tumor resection can make the margin unclear on MRI. Regardless of whether the surgical margins on MRI contain only capsule or tumor cells, the residual capsule itself could increase the risk of remnant tumor growth because the cleavage between the capsule and tumor cells is indistinct in spinal schwannomas [
20]. The diagnostic accuracy of the remnant tumor margin based on MRI findings needs to be further examined by mutually comparing intraoperative findings with postoperative MRI findings.
Though we revealed that the G group had a significantly higher age than the NG group (61.4 years vs. 47.6 years; p=0.04), higher age had a smaller influence on remnant tumor growth (OR, 1.08; 95% CI, 1.001–1.166; p=0.047) than the remnant tumor margin, and previous studies have not described significant correlations between age and remnant tumor growth. However, these findings at least support the importance of frequent MRI follow-up in elderly patients as well, especially when the remnant tumor margin is proximal. We unfortunately failed to explain the higher age in the G group, and this should be considered a limitation of this study.
Another limitation of this study is the small sample size and possible sample bias. Multivariate logistic regression analysis was not performed to investigate the independent predictors of remnant tumor growth because of the small sample size, and the univariate analysis performed in this study cannot exclude possible confounding factors. Additionally, another limitation of this study is the lack of quantitative analyses of preoperative and postoperative tumor size. Previous studies measured tumor size as the longest diameter of the tumor on axial MRI [
7,
11,
14,
21] and reported that preoperative and postoperative tumor sizes were not significant risk factors for remnant tumor growth [
7,
14]. However, discrepancies between measurements of tumor size only on axial MRI and the actual 3-dimensional tumor size were much concerned. Novel methods should be applied to evaluate the actual tumor size in the future studies. Finally, we failed to explain why the remnant tumor growth to extraforaminal direction, not only into the spinal canal, was rarely observed when the surgical margins were at zone 3. This mechanism cannot be cleared by the current study as well as by previous studies, and should be multifactorial (e.g., remnant tumor margin, MIB-1 index, remnant tumor size). Another potential factor might be the vascularity of cervical DS. Surgical devascularization of VS reportedly could lead to necrosis of the remnant tumor and reduce the chance of regrowth after IR [
22]. Similar mechanism might be applied to cervical DS. Cervical spinal arterial branches arise mainly from the VA, continue as radicular arteries passing through the intervertebral foramen, and then penetrate the dura to supply the nerve root and spinal cord as a major source of blood [
23,
24]. Cervical DS which has intracanalicular portion, all types other than type IIC by Toyama classification, might be mainly vascularized in the spinal canal. Therefore, resection of cervical DS distally away from the entrance of the intervertebral foramen by a posterior approach might devascularize the remnant tumor and inhibit its regrowth both into the spinal canal and to the extraforaminal direction. However, no study as yet has investigated the vascularity of cervical DS and this hypothesis needs to be further examined.