Ossifi ed Metaplastic Meningioma with Intratumoral Hemorrhage

Background: Metaplastic meningioma is a rare subtype of WHO grade I meningioma. Among the diverse types of mesenchymal differentiation seen in this tumor, the presence of extensive “ossifi ed change” or “ossifi cation” is rare. Most cases of osseous meningioma in the literature occurred in spinal level and intracranial location is relatively rare. The pathogenesis is postulated to be associated with increased level of intratumoral alkaline phosphatase.


Introduction
Metaplastic meningioma is a rare subtype of meningioma. By definition, the mesenchymal differentiation includes osseous, cartilaginous, lipomatous, myxoid or xanthomatous changes [1,2]. Nonetheless, this kind of tumor is benign and is classified as WHO grade I [1,2].. However, the morphologic changes in reported osseous meningioma vary from extensive distribution of psammomatous bodies within the tumor to the presence of mature bony trabeculae. The latter has to be distinguished from associated hyperostosis of adjacent skull, intraosseous meningioma, and periosteal osteoblastoma [3]. Intratumoral hemorrhage of meningioma is another phenomenon rarely observed. We report a case of ossified meningioma with the presence of both rare features.

Case Report
A 60-year-old man suffering from headache for 3 days and progressive weakness of left-sided limbs was admitted to our Neurosurgery Department. Neurologic examination showed decreased muscle power at left limbs. CT examination revealed a 3.1 cm heavily calcified lesion on right posterior frontal lobe ( Figure 1A). MRI imaging revealed a right temporal extra-axial mass with increased signal on T 1 and decreased T 2 -weighted sequences, suggestive of a heavily calcified tumor ( Figure 1B and 1C). The overlying calvarium showed hyperostosis. The association of the extra-axial mass with dural and osseous reaction as well as calcified fatty components led us to the clinical suspicion of an ossified meningioma or other brain tumors with calcifying elements. It also revealed some intratumoral and peripheral vasculature devoid of flow. A right fronto-temporal craniotomy was performed. The tumor showed adhesion to the overlying skull. The tumor and its dural insertion were completely removed. The postoperative course was uneventful, and there was no neurologic sequel.

Pathological findings
Gross inspection of the removed tissue revealed a tumor measuring 4.7 x 3.7 x 2.0 cm in size, with attached dura measuring 3.5 x 3.3 cm in dimensions. We observed a hemorrhagic area surrounded by hard bony tissue in the central portion of this tan and elastic tumor (Figure 2A). The tumor was composed of polygonal cells growing in a whorled pattern, suggestive of meningothelial-like cells. In some areas, there was a transition of the growth pattern showing fibroblast-like spindle cells in vague fascicular arrangement. Foci of erythrocyte extravasation and abundant deposition of hemosiderin granules, suggestive of previous intratumoral bleeding, were present within the tumor cells ( Figure 2B). An area of infarct was also seen. Large lamellated trabeculae of mature bone were seen within the tumor extensively. We also observed osteoblastic rimming ( Figure  2C). The tumor cells were positive for immunostains of EMA ( Figure  3A) and vimentin. The rich vascular background was also identified by the CD34 staining ( Figure 3B), but there was no endothelial proliferation or angiomatous vascularization present. The MIB-1 proliferative index was less than 5% .

Discussion
The first case of ossified meningioma in human occurred in the spinal cord and was reported by Roger in 1928 [4]. A review of the literature revealed that less than 25 cases of ossified meningioma had been reported from 1977 to 2005 [5]. The vast majority of these tumors are spinal location sometimes, extensive ossification in this intracranial tumor could mimic extensive hyperostosis, intraosseous meningioma, and periosteal osteoblastoma clinically [6]. Only 5 cases of intracranial meningioma were present in the literatures (see Table  1) and of only one demonstrated true bony trabeculae formation histologically. All the other case reports described tumors rich in psammoma bodies or calcification or located intraosseously.
The mechanism of ossification in meningioma is unclear. Typically, the arachnoid membrane contains frequent regions of microscopic calcification. It has been suggested that calcified meningiomas are, in fact, precursor lesions to ossified meningioma [7]. W. J. Pepler demonstrated a strong enzyme reaction of alkaline phosphatase in all cells comprising a meningothelial meningioma and the cells around the psammoma bodies in the psammomatous type [7].
Most meningiomas are benign and slow-growing tumors. Hemorrhage is a very rare presentation of meningiomas and the hemorrhagic patterns can be classified into three types: subarachnoid hemorrhage, intracranial hemorrhage/intratumoral and subdural hemorrhage [8]. The bleeding propensity of intracranial hemorrhage is highest when it is found in association with the meningothelial type [8]. However, Helle and Conley suggested that angioblastic meningiomas had bleedind tendency more than twice as frequently as all other types of meningiomas [9]. While clinically significant hemorrhage is associated with loss of consciousness, the surgeryrelated mortality rate in unsuspected meningioma with hemorrhage is similar to the cases without bleeding [10]. We do not know whether ossified meningiomas have bleeding tendency due to rare reported cases in the literatures. In addition, the image signal of hemorrhagic foci sometimes could be masked by the osseous background so that makes it hard to detect the intratumoral hemorrhage clinically. In our case, rich vascularity within the tumor is found and may explain its bleeding propensity. However, the true mechanism of hemorrhage in this osseous tumor is still unknown.
In summary, we report a rare case of ossified meningioma occurring in a 60-year-old man with unusual clinical manifestations. Extensive osseous change and multifocal intratumoral hemorrhage were distinct. The mechanism of ossification of meningioma is still unclear. The clinical doctors should take this rare tumor into the differential diagnosis when encountering the intracranial osseous tumors. In addition, pay attention to progressive neurologic changes which may imply the underlying tumor bleeding.