**7. Atypical meningiomas or WHO grade II**

According to the WHO classification of 2007, a growing subset of lesions (about one third) has the histopathological characteristics to be defined atypical, thus showing a more aggressive behavior [13].

The criteria to define atypical meningiomas are independent from meningioma subtype.

Atypical meningiomas are in fact described as lesions with one or more of these characteristics:


**•** necrosis

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‐

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

Complex cariotypes were found in 34% of benign meningiomas, 45% of atypical, and 70% of

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].

**6. Benign meningiomas or WHO grade I meningiomas**

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

In most of cases, WHO grade I meningiomas are diagnosed. They present a benign clinical course, with rare mitoses and occasional pleomorphic nuclei. Various architectural patterns have been described, whose most frequent are meningothelial, fibroblastic, and transitional meningiomas. Meningothelial or syncytial meningiomas are characterized by a high cellular density with cells disposed in packed sheets. Fibroblastic meningiomas are similar to schwan‐ nomas, with elongated cells. Cellular whorls and psammoma bodies (mineralized whorls) are most common in the transitional type, which present intermediate features between the meningothelial and the fibroblastic subtype. Other rare variants are the psammomatous meningiomas, characterized by multiple psammoma bodies, the angiomatous meningiomas,

cal progression [22].

366 Neurooncology - Newer Developments

more indolent biological behavior.

anaplastic meningiomas [24].

type 2a (hsst2a) [37].


Four subtypes of WHO grade II meningiomas have been described [11]: The chordoid meningioma is histologically similarto chordoma, with a mucin-rich stroma and clear vacuoles in epithelioid cells. This pattern is mixed with meningothelial or transitional tumor areas, and it is usually supratentorial. Castleman's disease has been reported in association with this

subtype [44]. The clear cell meningioma is composed by cells with glycogen-rich clear cytoplasm andextensive collagendeposition. This subtype typically occurs in the cauda equina region and in the posterior fossa. A high recurrence rate is characteristics. The atypical meningioma has atypical features and cannot be classified as chordoid or clear cell meningi‐ oma.

An association between the survival rate and the extent of resection for atypical meningio‐ mas was confirmed by multiple studies [45, 46]. Even if a maximal resection is the first aim of the surgery, these lesions are often less well delimited and a safe resection is often incom‐ plete because of bone infiltration and vascular invasion. Many studies are actually investigat‐ ing the real role of adjuvant therapies. If fact both radiotherapy and eventually chemotherapy are not free of side effects and even if they are commonly adopted for malignant meningio‐ mas, the balance benefits–risks is not yet assessed for atypical meningiomas.
