Introduction

Sphenoid wing meningiomas are benign tumors with slow growth rates, and the majority of these tumors correspond histologically to World Health Organization (WHO) grade I [19, 23]. Despite this, sphenoid wing meningiomas are biologically complex and can be clinically challenging [11, 24]. Complete surgical resection is the primary treatment modality, with radiation being the only accepted form of adjuvant therapy [14, 20]. Mathiesen et al. found a strong correlation between the extent of surgical resection and the rate of recurrence in patients with skull base meningiomas [16]. However, radical surgical treatment of skull base meningiomas presents several difficulties since these tumors may involve critical neurovascular structures [9, 10, 19]. Accordingly, surgical resection of these tumors causes considerable morbidity and mortality rates [7, 9, 13, 19], which tend to be higher with aggressive compared to conservative surgery [16]. To select the adequate surgical strategy, it is mandatory to collect the available data regarding the anatomical localization of the tumor and the extent of morphological alterations of the adjacent brain and bone as detected by MRI and CT imaging [6, 7, 13]. We hypothesized that a specific pattern of tumor extension as defined by the affection of certain anatomical structures can be predictive for reduced resectability, higher complication and recurrence rates. The goal of our study was therefore to evaluate the anatomical pattern of tumor growth in patients with sphenoid wing meningiomas and classify the findings using anatomical landmarks. The results of this analysis were correlated with the extent of resection and frequency of recurrence.

Materials and methods

We retrospectively analyzed 44 patients [7 male (15.9%) and 37 female (84.1%)] with sphenoid wing meningiomas who received microsurgical tumor resection between 1993 and 2002. All tumors were classified as global medial sphenoid wing meningiomas according to the modified Cushing classification [22]; no meningioma en plaque was included. The median age was 64 years (range: 43–78 years). A team of seven different neurosurgeons performed the resection in all of the cases. To assess intraoperative findings, the surgery reports were reviewed, which were formulated in a standarized fashion. Thus, the intraoperative findings of tumor extension into the surrounding tissue accurately reflected the results of the preoperative CT and MRI imaging. The extent of resection as described in the reports was graded using the Simpson classification [25] as described in Table 1. Patients received a control MRI scan 3–4 months after surgical resection to assess the extent of resection while avoiding surgery-induced tissue artifacts. The results of the postoperative MRI imaging confirmed the intraoperative resection status as expressed by Simpson grading in all cases. After this baseline scan, regular control MRI scans were performed on an annual basis. The mean time of follow-up was 9.2 years; no patient was lost for follow-up. In a situation of incomplete resection (Simpson grade III–V), recurrence has been defined as significant enlargement of the residual lesion, whereas after complete resection (Simpson grade I and II), major changes in MRI or CT scanning indicative for recurrent tumor growth were viewed as recurrence.

Table 1 Simpson grading scale of tumor resection [14]
Full size table

To evaluate the soft tissue extension pattern, magnet resonance imaging (MRI) was performed with a 1.5-T scanner. The protocols included an axial T2-weighted spin-echo sequence, a proton density-weighted spin-echo sequence and axial and coronal T1-weighted gradient-echo sequence before and after application of gadolinium-DTPA. In most cases, soft tissue extension of the tumor was defined by T1-weighted, contrast-enhanced abnormalities within the affected structure. Bone infiltration was analyzed on CT scans at bone window levels and defined as lytic, sclerotic or hyperostotic changes of the bone. For the evaluation of soft tissue extension, we focused on four anatomical landmarks, whereas for the assessment of bone infiltration, eight different landmarks were analyzed. These landmarks partly represent gateways for normal structures to penetrate from the anterior and middle cranial fossa into the orbita, which can be utilized by the tumor as an extension pathway. In addition, descriptive studies have shown that specific structures of both brain and bone tissue are more preferrably infiltrated by meningioma cells compared to others [2, 4]. Thus, the landmarks were chosen based on the potential extension pattern and the relative frequency of specific structures to be affected by the tumor. The investigators analyzing the extension patterns were blinded to the underlying histology and outcome data.

Histologic diagnosis of the tumor samples was performed by an independent pathologist. The histology as well as grade of malignancy according to the WHO grading system are described in Table 2. MIB-1 labeling was performed by incubating the sections with a monoclonal anti MIB-1 antibody (AMAC, Westbrook, ME) at a concentration of 1:100. Detection of antibody binding was performed using the avidin-biotin complex method according to the supplier directions (Vector Laboratories, Burlingame, CA). As a control sample, sections on the same slides were incubated with non-immune mouse IgG at identical protein concentrations. For the MIB-1 labeling index, the positive cells were counted in a high power vision field and expressed as percentage of the total number of cells per vision field.

Table 2 Histology and malignancy grade of sphenoid wing meningiomas
Full size table

Comparative statistical analysis was performed for rates and proportions using chi-square analysis or a two-tailed Fisher's exact test. For the comparison of several different groups, one-way analysis of variance (ANOVA) on ranks with subsequent all pairwise multiple comparison (Dunn’s method) was computed (SigmaStat Version 3.0, SPSS Inc., Chicago, IL).

Results

Complete resection including the dural attachment and invaded bone (Simpson grade I) was performed in 22.7% of all cases. In all patients in which the dural attachment was resected, dural reconstruction was performed. However, in the majority of the cases, a Simpson grade II resection was achieved (Table 1). In the group of radically resected tumors (Simpson grade I and II), only three recurrences were observed. Interestingly, all of these cases showed a specific pattern of bony infiltration of the orbital roof and the superior orbital fissure in the initial scans. Of all the patients, 29.5% showed significant perioperative morbidity. Morbidity was related to cranial nerve dysfunction in six cases (13.6%) affecting CN III, IV and VI, postoperative hemorrhage in four (9.0%), stroke in two (4.5%) cases and CSF fistula in one (2.3%) case. The morbidity rates did not correlate with the extent of resection (p > 0.05). The mortality rate was 11.4%, with pulmonary embolism (PE) as the most frequent cause of death (three cases). The vast majority of the cases showed a meningothelial differentiation and were classified as WHO grade I. Only four cases with atypical and anaplastic differentiation (WHO grade II and III, respectively) were seen in our patient population (Table 2). As expected, the MIB-1 labeling indices were significantly higher in the atypical and anaplastic tumors compared to the benign tumors classified as grade I WHO (p = 0.002).

All of the analyzed patients showed expansive growth into adjacent structures, we did not observe a purely circumscript lesion. The soft tissue extension was evenly distributed throughout the cases. About one third of the patients showed invasion of the tumor into the analyzed anatomical landmarks. Quite frequently we observed a simultaneous extension into multiple regions (Table 3a). In contrast, the bone infiltration displayed a more differentially distributed pattern. The temporal and cerebral surfaces of the temporal bone were the most frequently affected regions, followed by the superior orbital fissure (Table 3b). The vast majority of the cases showed sclerotic or hyperostotic changes of the bone. Interestingly, about 20% of all cases displayed significant invasion of the bone within the superior orbital fissure as shown by CT scans, despite no signs of soft tissue extension as indicated by high-resolution MRI (Fig. 1).

Table 3 Soft tissue extension, bone invasion, and extension pattern and recurrence
Full size table
Fig. 1
figure 1

Preoperative MRI (a) and CT (b) scan of the skull base of a patient with a global medial sphenoid wing meningioma. The MRI scan shows no signs of tumor extension into the superior orbital fissure, whereas the high-resolution non-enhanced CT scan displays intense bone infiltration of the same region (arrow)

Full size image

Tumor recurrence in Simson grade I and II cases or regrowth of residual lesions in grade III-V cases was observed in 13 patients (29.5%). Four patients with recurrent tumors received radiotherapy during follow-up; no systemic treatment such as chemotherapy or hormonal therapy was applied. The mean time to recurrence was 26.2 months (range: 9–65 months). As expected, extent of resection as shown by Simpson grading was strongly associated with recurrence (p = 0.01). None of the patients without bone infiltration (n = 7) showed any recurrence, whereas all 13 cases presenting with recurrent tumors showed bone infiltration in the initial imaging. Three of the 15 patients with cavernous sinus infiltration showed recurrent tumor during the follow-up phase. Thus, soft tissue growth into the cavernous sinus and bony infiltration of the superior orbital fissure and the orbital roof was highly predictive for tumor recurrence (p = 0.002). In addition, tumor recurrence was significantly related to histological grading (p = 0.014) and the MIB labeling index (p = 0.021). However, after stratification for malignancy grading, the MIB-1 labeling index was no longer significantly correlated with recurrence (p = 0.92), whereas bone infiltration of the orbital roof and the superior orbital fissure was still highly predictive for tumor recurrence (p = 0.01).

Discussion

In his landmark paper, Simpson reported a strong correlation between the extent of resection and the frequency of recurrence in meningiomas [25]. Since then, this aspect has been consistently confirmed in a number of studies [5, 12, 15–17]. However, despite continuous improvement of microsurgical resection, a certain subset of sphenoid wing meningiomas shows a significant tendency to recur [16]. To date, there is no appropriate clinical or histological marker that can predict aggressive behavior in these tumors [3, 23]. Traditional grading of malignancy has limited value as a prognostic factor, since the majority of sphenoid wing meningiomas histologically correspond to WHO grade I [11]. The impact of histological subtypes on the outcome has been controversial. Crompton et al. [8] suggested that syncytial meningiomas are most likely to recur and fibroblastic least so, but the results of Adegbite directly contradict these findings [1]. Utilizing the proliferation marker MIB-1, we detected significant differences between benign and malignant tumors, but did not find a prognostic value of this marker within the grade I WHO tumors, which constitute over 90% of our study population. In contrast, we could show that bone infiltration of the orbital roof and the superior orbital fissure was a highly predictive factor for recurrence in WHO grade I tumors. Our results therefore demonstrate that a specific pattern of tumor growth within certain structures of the skull base is highly predictive for worse surgical outcome and higher rates of recurrence. There are two different main hypotheses that may explain these findings. First, it is possible to speculate that the invasion pattern reflects the pathoanatomical phenotype of a specific subgroup of tumors that have a different, more aggressive biology [21]. Secondly, the tumors in this particular region causing soft tissue invasion of the cavernous sinus as well as intense bone infiltration of the orbital roof and the superior orbital fissure may represent an anatomical location with limited surgical accessibility. In our study we have found a mortality rate of 11.4%, with pulmonary embolism (PE) as the most frequent cause of death (three cases). More recent studies analyzing the outcome of anterior skull base meningiomas have reported mortality rates of 0% [18], 1.4% [21] and 11.5% [19]. The patient age was significantly younger in the first two studies, which may be related to the difference in mortality. We did not observe any other clinical condition in our patient population that might be related to a higher risk of PE. In conclusion, we propose that the analysis of a specific growth pattern in patients with sphenoid wing meningiomas may be useful to detect patients with a higher risk of recurrence requiring a more thorough postoperative follow-up and management.