**5. Genetic and molecular profiles**

**4. Radiology**

364 Neurooncology - Newer Developments

gioma.

features of the lesion.

Meningiomas present as well-defined extra-axial lesions with a typical peripheral CSF cleft. They present a homogeneous contrast enhancement on CT- and T1-weighted MRI with gadolinium administration. The tumor has a dural or bone implantation and a typical dural tail (contrast enhancement of the dura adjacent to meningioma implantation) (Figures 3 and 4). A reactive sclerosis of the underlying bone may be present in about half of skull-base meningiomas [17]. In rare cases, bone erosion is present (**Figure 5**). Calcifications or cystic portions may be present. Hyperintensity in T2-weighted MRI may denote a higher water

**Figure 3.** T1-weighted coronal (a) and axial (b) MRI with gadolinium administration showing a well-defined extra-ax‐ ial lesion with an homogeneous enhancement and a contiguous dural enhancement (dural tail). A subtle CSF cleft is also visible between the lesion and the cerebral surface. These radiologic findings are typical for a convexitary menin‐

**Figure 4.** A tentorial meningiomas with less demarcated limits and probably infiltrating the adjacent brainstem. The dural tail is evident in this T1-weighted MRI post gadolinium administration. This 33-year-old patient was irradiated during infancy after the resection of an ependymoma of the IVth ventricle. This may help in explaining the atypical

content and thus an easily resectability during surgery.

More than a half of sporadic meningiomas of every histological grade have a mutation in NF2 gene on the chromosome 22q12, coding for merlin (moesin–ezrin–radixin-like protein), and it is considered an early event in tumorigenesis [18]. Merlin seems to interact with transmembranous proteins to activate pathways promoting cell proliferation. Its expression may vary, however, according to meningioma's subtype [19]. The product of the DAL-1 gene, a member of the protein 4.1 family, has also been supposed to be implicated in meningioma tumorigenesis and progression. The prevalence of mutations of protein 4.1B was not differ‐ ent among WHO grades, and it may be an early event in meningioma tumorigenesis [20].

Aside 22q deletions, multiple genetic mutations are observedin meningioma progression, such as loss of heterozygosis in 1p, 3p, 6q, 9p, 10q, and 14q [21] and are associated with histologi‐ cal progression [22].

Recently, the analysis of microRNAs (miRNAs) profiles was identified as a potential tool to define the natural history of different meningiomas. A low expression of miR-29c-3p and miR-219-5p was associated with more aggressive phenotypes and with a higher risk of recurrence [23]. On the contrary, high expression of miR-145 seems to be associated with a more indolent biological behavior.

Complex cariotypes were found in 34% of benign meningiomas, 45% of atypical, and 70% of anaplastic meningiomas [24].

Proliferative markers such as MIB-1 and Ki67 have been associated with a more aggressive biological behavior in some studies [25, 26]. The relationship between genetic and molecular alterations and recurrence is a matter of debate: According to Sandberg et al. [26], the recurrence rate seems to be associated to proliferative markers and Ki-67 and cyclin B1 genes were overexpressed in recurrent meningiomas [27, 28], with a significant association be‐ tween Ki-67 and tumor recurrence [29]. Contrasting results exist, however, on this argument, as Aguiar et al. [30] did not find any association between MIB-1 and the histological grade. Other markers have also been investigated, such as p53, TGFalpha, and beta, PDGF [25, 31]. EGFRs are overexpressed in about 60% of meningiomas, while VEGF is also upregulated in meningioma cells but no association with the WHO histological grade was observed [32]. The invasiveness of meningioma cells has been linked to the expression of matrix-metalloprotei‐ nase-9 (MMP-9), and its expression may be a prognostic marker for recurrence [33].

In 1979, Donnell et al. [34] were the first to describe the role of estrogen receptors in meningi‐ omas development. However, over the time, progesterone receptors showed to have a higher expression in meningioma cells and their level was correlated to a favorable clinical behav‐ ior [35]. Also the expression of E-cadherin was more elevated in benign meningiomas [36].

Furthermore, about 70–100% meningiomas express somatostatin receptors, predominantly the type 2a (hsst2a) [37].
