SMARCE1 mutation screening in classification of clear cell meningiomas

Clear cell meningioma (CCM) is a rare subtype of meningioma and shows not only unusual histology, but also unique clinical features. Recently, SMARCE1 mutations have been shown to cause spinal and cranial CCMs. We present 12 cases which were diagnosed with CCM in a single institution between 1997 and 2014, and investigate their SMARCE1 mutation status.

To investigate the SMARCE1 mutation status of these tumours, we used a combination of Sanger sequencing and multiplex ligation-dependent probe amplification analysis and also performed SMARCE1 immunohistochemical staining. We found both SMARCE1 mutational hits, including novel SMARCE1 mutations, in six of eight tested patients. Immunohistochemical analysis showed loss of SMARCE1 protein staining in all but two cases. Two individuals who were diagnosed originally with CCM were negative for SMARCE1 mutations, but tested positive for NF2 mutations. As a result, these two tumours were re-analysed and eventually reclassified, as a microcystic and a mixed pattern of meningothelial meningioma with focal clear cell areas, respectively.

These results expand the spectrum of pathogenic variants in SMARCE1 and show that mutation screening can help to facilitate meningioma classification. This may have implications for prognosis and future clinical management of patients, as CCMs are classed as grade II tumours, while microcystic and meningothelial meningiomas are classed as grade I.