CDKN2A is a tumor suppressor gene encoding the p16 protein, a key regulator of the cell cycle. CDKN2A homozygous deletion is a central prognostic factor for numerous tumors and can be detected by several techniques. This study aims to evaluate the extent to which immunohistochemical levels of p16 expression may provide information about CDKN2A deletion. A retrospective study was conducted in 173 gliomas of all types, using p16 IHC and CDKN2A fluorescent in situ hybridization. Survival analyses were performed to assess the prognostic impact of p16 expression and CDKN2A deletion on patient outcomes. Three patterns of p16 expression were observed: absence of expression, focal expression, and overexpression. Absence of p16 expression was correlated with worse outcomes. p16 overexpression was associated with better prognoses in MAPK-induced tumors, but with worse survival in IDH-wt glioblastomas. CDKN2A homozygous deletion predicted worse outcomes in the overall patient population, particularly in IDH-mutant 1p/19q oligodendrogliomas (grade 3). Finally, we observed a significant correlation between p16 immunohistochemical loss of expression and CDKN2A homozygosity. IHC has strong sensitivity and high negative predictive value, suggesting that p16 IHC might be a pertinent test to detect cases most likely harboring CDKN2A homozygous deletion.

Meningioma is the most common adult primary intracranial tumor. Malignant meningioma is a rare variant of meningioma. The prognosis for the patients with these tumors is poor, due to the tumor’s capacity for relapse and to develop distant metastases. These tumors can present the same evolutionary course as aggressive carcinoma. We report the case of distant brain and gastro-intestinal tract (GIT) metastases. A 78-year-old patient developed malignant meningioma with a Ki-67 proliferative index of 40%. According to guidelines, surgery followed by postoperative radiotherapy (RT) was performed. Three months after the end of RT, he presented histologically proven meningioma distant brain and GIT metastases. To our knowledge, this is the first case of meningioma GIT metastases. Also, we report the difficulty to confirm the diagnosis of meningioma metastases. Indeed, malignant meningioma has the same histopathological features as melanoma or carcinoma. The standard of care for the management of malignant meningioma is gross total surgery followed by postoperative radiotherapy. Metastatic meningioma is uncommon and no guidelines for the management of recurrent or metastatic meningioma have yet been published. However, several studies reported systemic therapeutic options such as antibody against VEGF, somatostatin analogs, PDGF-R, and VEGF-R tyrosine kinase inhibitors, in the case of recurrent or metastatic meningioma. We also made a review of the actual literature of systemic treatment options for metastatic meningioma.

Background: The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. Methods: we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. Results: In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7–10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). Conclusions: Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.