Abstract
Meningioma is a primary brain tumor arising from the neoplastic transformation of meningothelial cells. Several histological variants of meningioma have been described. Here we show that NHERF1/EBP50, an adaptor protein required for structuring specialized polarized epithelia, can distinguish meningioma variants with epithelial differentiation. NHERF1 decorates the membrane of intracytoplasmic lumens and microlumens in the secretory variant, consistent with a previously described epithelial differentiation of this subtype. NHERF1 also labels microlumens in chordoid meningioma, an epithelial variant not previously known to harbor these structures, and ultrastructural analysis confirmed the presence of microlumens in this variant. NHERF1 associates with the ezrin-radixin-moesin (ERM)-NF2 cytoskeletal proteins, and moesin but not NF2 was detectable in the microlumens. In a meningioma series from 83 patients, NHERF1 revealed microlumens in 87.5% of the chordoid meningioma (n = 25) and meningioma with chordoid component (n = 7) cases, and in 100% of the secretory meningioma cases (n = 12). The most common WHO grade I meningioma variants lacked microlumens. Interestingly, 20% and 66.6% of WHO grades II (n = 20) and III (n = 3) meningiomas, respectively, showed microlumen-like NHERF1 staining of ultrastructural tight microvillar interdigitations, mainly in rhabdoid, papillary-like or sheeting areas, revealing a new subset of high grade meningiomas with epithelial differentiation. NHERF1 failed to detect microlumens in 12 additional cases of chordoid glioma of the 3rd ventricle, chordoma and chondrosarcoma, neoplasms that may mimic the histological appearance of chordoid meningioma. This study uncovers features of epithelial differentiation in meningioma and proposes NHERF1 immunohistochemistry as a method of discriminating chordoid meningioma from neoplasms with similar appearance.
Highlights
Meningiomas are common primary central nervous system (CNS) tumors that derive from meningothelial cells
We show that NHERF1/EBP50, an adaptor protein required for structuring specialized polarized epithelia, can distinguish meningioma variants with epithelial differentiation
In addition to intertumoral heterogeneity, intratumoral variation frequently occurs, with combinations of histologic variants seen in individual neoplasms
Summary
Meningiomas are common primary central nervous system (CNS) tumors that derive from meningothelial cells. Thirteen histologic variants of meningioma are recognized in the WHO Classification of Tumors of the CNS [1]. Most of the variants have low recurrence rates, and are considered WHO grade I neoplasms. Four of these variants are important to distinguish because they portend a worse prognosis: these aggressive variants include chordoid and clear cell meningioma (WHO grade II), as well as papillary and rhabdoid meningioma (WHO grade III). Neoplastic meningothelial cells may undergo differentiation towards a fibroblastic or an epithelial phenotype. Two histologic variants are currently known to demonstrate epithelial differentiation: secretory and chordoid [2, 3]. Ultrastructural studies have described membranes containing microvilli in both variants [2, 3]
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