**5. Risk factors at initial diagnosis**

Several pathological, neuroradiological and surgical findings at initial diagnosis are correlated to the meningioma recurrence. However, which factors may be considered at risk of multicentric-diffuse recurrence are not defined.

#### **5.1 Location**

The meningioma location is a significant risk factor of recurrence. Medial skull-base meningiomas include locations, such as olfactory groove, tuberculum sellae, anterior clinoid, foramen magnum, with low recurrence rates (0–15%) [36–38]. Besides, the low recurrence rate of spinal meningiomas is well known (0–10% in 15 among 19 reviewed series in our recent study [39]). On the other hand, the reported recurrence rates are higher for lateral skull-base (35–40% for lateral sphenoid wing and mainly spheno-orbital [38–40]) and for non-skull base meningiomas (16 to 24% for parasagittal and falcine) [23, 41].

However, when the rates of multicentric-diffuse recurrences are considered, the differences for intracranial tumor locations are not relevant. Although in our study [28] spheno-orbital and parasagittal meningiomas show higher rates of multicentric and diffuse recurrences, this finding does not reach significance. Our series does not include diffuse recurrences of spinal meningiomas; this agrees with the well known better biological behavior of this location.

Thus, the meningioma location is correlated with the rate but not with the growth pattern of the recurrences.

#### **5.2 Shape**

The shape of meningiomas may be variable. According to the rate height/base on magnetic resonance imaging, the meningiomas may be classified as round (rate > 1) and flat-shaped (rate ≤ 1). Flat-shaped meningiomas are characterized by prevalent and often extensive dural involvement as compared to round-shaped ones. Thus, it has been shown that flat-shaped meningiomas are more likely to recur than round ones [22, 24].

The flat-shaped morphology at initial diagnosis was the only radiological finding at significantly higher risk of multicentric diffuse recurrence as compared to local-peripheral recurrence in our study (p = 0.0008) [28]. Thus, it is like that flatshaped meningiomas are associated to various degree of even distant microscopic dural infiltration.

*Topographic Distribution of Intracranial Meningioma's Recurrences: Localized Versus Diffuse… DOI: http://dx.doi.org/10.5772/intechopen.97120*

## **5.3 Dural tail**

The change of the peritumoral dura mater depicted on the postcontrast magnetic resonance studies and defined as "dural tail" is known since its description in 1989 [42]. It may correspond to various histopathological patterns, including increased loose connective tissue, angiogenesis, dilated vessels, reactive hyperplasia, tumor invasion [42, 43]. Qi et al. [30], in a large series of convexity meningiomas, described several types of dural tail with different histological aspects: smooth (uniformly extended) with tumor extension up to 1,5 cm; nodular, with nodular hyperplasia corresponding to tumor nodules and tumor extension to the distal dura up to 2,5 cm; mixed, with nodular enhancement proximal to the dural attachment and distal smooth enhancement. In spite of the presence of tumor cells nodules, the finding of dural tail was found to be not correlated to the meningioma recurrence in most studies [9, 19, 22]. We did not investigate this finding in our series of multicentric-diffuse recurrences; however, we suggest that further studies will define this aspect.

## **5.4 Brain-tumor interface**

The brain-tumor interface, more often well preserved during meningioma surgery, may be unclear or lost, often with variable pial invasion, as in WHO grade II tumors. In such cases the tumor resection may be incomplete, with residual nodules mainly in critical regions. This may increase the risk of recurrence at the initial site or at the surrounding region [10, 14, 22]. On the other hand, the presence of the residual cell nests at the brain-tumor interface does not explain the recurrences in distal dural regions and the diffuse regrowths.

#### **5.5 Extent of surgical resection**

The entity of the resection at initial surgery is mostly considered a major risk factor for recurrence [23, 44, 45]. However, the clinical usefulness of the Simpson grading in general has been questioned, at least for benign meningiomas. Some studies found no statistically significant differences in progression-free survival between Simpson grades 1 to 4 [46] and 1 to 3 [13, 47] resections for WHO I grade meningiomas. This discrepancy may reflect the technical surgical improvement and the smaller tumor remnants in incomplete resections. In a recent report Haddad et al. [48]. found that patients with WHO grade I meningiomas and Ki67-MIB1 > 4,5% treated by gross total resection had similar risk of recurrence as those patients with subtotal resection. In this study, early recurrences were more significantly impacted by extent of resection, whereas the Ki67-MIB1 was more significant for later recurrences.

In our study on multicentric-diffuse recurrences [28], their rate is not impacted by the extent of resection at initial surgery.

#### **5.6 Multiple meningiomas**

Multiple meningiomas account for 2 to 8% of all meningiomas [49]. They may be diagnosed either initially or during the neuroradiological follow-up.

In a large metanalysis of the literature on multiple meningiomas, Pereira et al. [49] found recurrence rate of 8.07% and no higher with respect to single ones. On the other hand, in the study by Gousias et al. [45] multiple meningiomas showed higher recurrence rate and significantly lower progression-free survival than single ones.

Multiple meningiomas likely develop from multicentric dural tumor foci according to the Borovich [29] theory. A similar mechanism is suggested for multicentric recurrences. In our study on multicentric-diffuse recurrences two patients had multiple meningiomas (two lesions) at initial diagnosis, with no significant differences with local-peripheral ones. We think that further studies on the long-term follow-up of patients operated on for multiple meningiomas will defined the recurrence rates and patterns of these cases.

## **5.7 Pathological findings**

In our study [28] meningiomas with values of Ki67 Li ≥ 4% are related to major risk of multicentric-diffuse recurrence, while the WHO grade (I versus II) is not significant. Several reports [7, 25–27] confirmed the relationship between higher Ki67-Li values and lower PR expression, and higher recurrence risk for intracranial meningiomas. However, in this study the PR expression is not correlated with the pattern of diffuse regrowth. Both these findings have not previously been reported.

The higher initial values of Ki67 Li of meningiomas recurring as diffuse forms suggest that even small dural tumor foci, even distant from the primary tumor site, may diffusely regrow.

Several studies have found that different genetic profiles and chromosomal abnormalities correspond to different meningioma subtypes with different aggressiveness and recurrence's rate [50–54], making speculate the existence of characteristic biomolecular profiles for meningiomas which recur in multicentric-diffuse pattern.
