The immunohistochemical loss of histone H3 trimethylated in lysine 27 (H3K27me3) was recently shown to predict recurrence of meningiomas after surgery. However, its association with tumor progression after stereotactic radiosurgery (SRS) is unexplored. To investigate whether H3K27 methylation status may predict progression-free survival (PFS) after SRS, we assessed H3K27me3 immunoexpression in thirty-nine treatment naïve, intracranial, meningiomas, treated with surgery and subsequent SRS for residual (twenty-three cases) or recurrent (sixteen cases) disease. H3K27me3 immunostaining was lost in seven meningiomas, retained in twenty-seven and inconclusive in five. Six of the seven meningiomas (86%) with H3K27me3 loss had tumor progression after SRS, compared to nine of twenty-seven (33%) with H3K27me3 retention (p = 0.0143). In addition, patients harboring a meningioma with H3K27me3 loss had significantly shorter PFS after SRS (range: 10–81 months; median: 34 months), compared to patients featuring a meningioma with retained H3K27me3 (range: 9–143 months; median: 62 months) (p = 0.0036). Nonetheless, tumor sagittal location was the only significant prognostic variable at multivariate analysis for PFS after SRS (p = 0.0142). These findings suggest a previously unreported role of H3K27me3 as a predictor of meningioma progression after SRS for recurrent or residual disease. Modulation of H3K27 methylation status may represent a novel therapeutic strategy to induce radiosensitization of meningiomas.

Introduction: The group of so-called “sellar-region masses” consists of a heterogeneous group of neoplasms and tumor-mimicking lesions, whose differential diagnosis may be challenging due to the overlapping of clinical and radiological features, which can be found both in “common” and “uncommon” lesions. The choice of a correct treatment strategy is still arduous and requires histological analysis. Gamma Knife Radiosurgery (GKRS) has already been reported as a safe and effective treatment in these cases. The objective of this study is to evaluate single-center pre-operative data, post-operative outcomes, and long-term follow-up in patients treated with GKRS for unusual sellar tumors. Methods: We retrospectively identified and analyzed nine patients treated with GKRS from 2004 to 2015, according to a standard protocol. Lesions consist of hypothalamic hamartoma (HH), Rathke’s cleft cist (RCC), Langerhans cell histiocytosis (LCH), spindle cell oncocytoma (SCO), choroid plexus papilloma (CPP), and ossifying fibroma (OF). The diagnosis was histologically confirmed in six patients that underwent surgery, while in three patients, diagnosis was based on characteristic clinical and radiological findings (two HH and one RCC). Pre-operative and post-operative data were retrieved from medical archives, and long-term follow-up was obtained through clinical and neuroradiological periodic examination. Results: In our series, all the “rare” sellar lesions treated, had a successful radiographic and clinical response in a medium-long follow-up period. Conclusions: The long-term follow-up results suggest that GKRS is a safe and effective treatment in rare sellar lesions, with very low toxicity. To the best of our knowledge, this report represents the largest series of unusual sellar lesions treated with GKRS in a single high-volume center, suggesting that GKRS might be an effective non-invasive adjuvant treatment option. Further studies and a larger number of patients are needed to confirm if residuals of these rare sellar lesions might regress on their own without treatment or if other non-invasive treatments could be as effective as GKRS.