Meningiomas usually arise in the cranial cavity or spinal canal. On the other hand, because meningiomas arise from arachnoid cells present in the meninges, they can occur in any location where meninges or ectopic meninges exist. Primary ectopic meningiomas are extremely rare pathological entities and have been reported sporadically. They usually occur in cephalic and paravertebral soft tissues and skin and, more rarely, in the ear [9
], temporal bone [9
], mandible, foot [2
], lung [10
], and mediastinum [5
]. The histopathogenesis of ectopic meningiomas is still unclear. However, three hypotheses are that they arise from an extension of the arachnoid cells along cranial nerve sheaths during development, from the arachnoidal cells trapped in extracranial locations when the skull bone fuses, or from differentiation of Schwann cells into meningocytes [1
To make a definite diagnosis of an ectopic meningioma is difficult, and such a diagnosis can only be made on the basis of microscopic morphological and immunohistochemical findings. In this case, and despite the unusual location of the tumor, the morphological and immunohistochemical findings closely resembled a meningioma in the central nervous system. Furthermore, as there was no clinical or radiological evidence of any intracranial or intraspinal lesion, we concluded that the meningioma in this case was of complete mediastinal origin.
In view of the rarity of extracranial meningiomas, caution must be used in ruling out possibilities in the differential diagnosis. Regarding the histological differential diagnosis of epithelial thymomas, they are composed of cells with large numbers of desmosomes often containing numerous cytoplasmic cytokeratin filaments in the desmosomes per se and lying free in the cytoplasm [13
]. Cytokeratin filaments are absent in meningiomas. Because of its morphological findings, as typical whorl formation for fibrous meningiomas, solitary fibrous tumors, schwannomas, and hemangiopericytomas could be diagnosed by exclusion. Additionally, hemangiopericytomas could be excluded by positivity of EMA in immunohistochemical results, because EMA stains show typically positive in meningiomas and negative in hemangiopericytomas. Positivity of EMA was compatible with the diagnosis of this tumor as a meningioma. Furthermore, leiomyomas could be excluded by negativity of αSMA in immunohistochemical results.
Histological grading of meningiomas is based on the 2007 WHO classification [14
]. Atypical meningioma (WHO grade II) shows increased mitotic activity or three or more of the following histological features: increased cellularity, small cells with a high nuclear/cytoplasmic ratio, prominent nucleoli, uninterrupted patternless or sheet-like growth, and foci of spontaneous or geographic necroses. Increased mitotic activity is defined as four or more mitoses per 10 hpf. In addition, brain invasion was included in an otherwise grade I tumor as an additional criterion for a WHO grade II lesion [14
]. In our case, the presence of small cells, spontaneous and zonal necroses, invasion into the pulmonary parenchyma, and mitotic activity of the tumor (four mitotic cells per 10 hpf) correspond histologically to an atypical meningioma. Expression of proliferation markers, such as MIB-1 and Ki-67, has generally shown progressive increases in the labeling index with a WHO grade from 1.00-1.35% for grade I to 1.90-9.30% for grade II or atypical meningiomas and 5.60-19.5% for grade III or anaplastic meningiomas [15
]. In addition, the median MIB-1 proliferation indices are 3.4% in ordinary meningiomas, 6.6% in atypical meningiomas, and 11.8% in malignant meningiomas [17
]. These data further support the classification of the meningioma in this case into an atypical category.
As for the clinical course, the surgical excision was as curative as a complete resection with a sufficient surgical margin. Although this was an atypical meningioma with invasion into lung tissue, no adjuvant therapies, such as radiotherapy, were performed. This decision was based on the fact that Mair et al. retrospectively reviewed the records of 114 consecutive patients with diagnosed WHO grade II meningiomas and reported that radiotherapy for WHO grade II atypical meningiomas was not appropriate after a first-time resection of those lesions in which a gross-total resection has been achieved [18
]. In addition, we consulted with the neurosurgeons of Gunma University Hospital, who were experienced in the treatment of cerebral meningioma.
According to our review of the literature, this is the first reported case of primary mediastinal atypical meningioma [Table ]. Of all the reported cases of mediastinal meningiomas, only one was malignant. All but one was surgically treated alone. The exception was treated with consecutive radiation after surgical resection. Regarding the clinical course of these cases, including this case, every case was disease-free for at least 9 months after surgery except for two cases for which the clinical course was not discussed. Although a longer follow-up is necessary, the findings strongly suggest that surgical resection is an acceptable and adequate treatment for ectopic mediastinal meningiomas.
Clinical features of reported primary mediastinal meningiomas.