Purpose: TERT promoter mutation (TERTp^Mut) has a strong association to recurrence and has been suggested to act as a driver mutation for malignant transformation of WHO grade I and II meningiomas. TERTp^Mut has been investigated in selected high‐grade meningioma samples. The existence of TERTp^Mut across recurrent tumors in a population‐based cohort needs to be investigated in order to identify when TERTp^Mut emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors. Methods: We gathered material from a consecutive single‐center cohort of 40 patients with malignant meningioma (WHO grade III) treated between 2000 and 2018, including specimens from primary and secondary malignant meningiomas with the corresponding earlier benign specimens and later malignant recurrences. In total 107 tumor samples were studied by Sanger sequencing for TERT promoter mutational status. Results: Seven of 40 patients (17.5%) harbored TERTp^Mut thus validating the incidence of TERTp^Mut in previous non‐population‐based cohorts. In 6/7 patients, the TERTp^Mut was present at initial surgery (WHO grade I–III) while in one patient the TERTp^Mut was found de novo when the meningioma became malignant. The incidences were 2/1.000.000/year for TERTp^Mut WHO grade III meningioma and 8/1.000.000/year for TERTp^wt WHO grade III meningioma in our catchment area. We found a 1.7 times higher recurrence rate (CI 95% 0.65–4.44) and a 2.5 higher mortality rate per 10 person‐years (CI 95% 1.01–6.19) for TERTp^Mut compared to TERTp^wt. Conclusion: TERTp^Mut can occur independently of malignant progression in meningioma and was most often present from the first tumor sample across recurring tumors. TERTp^Mut in WHO grade III may represent a marker of an aggressive subset of tumors.

Background: In recent years, it has become evident that the tumoral microenvironment (TME) plays a key role in the pathogenesis of various cancers. In meningiomas, however, the TME is poorly understood, and it is unknown if glia cells contribute to meningioma growth and behaviour. Objective: This scoping review investigates if the literature describes and substantiates tumour–brain crosstalk in meningiomas and summarises the current evidence regarding the role of the brain parenchyma in the pathogenesis of meningiomas. Methods: We identified studies through the electronic database PubMed. Articles describing glia cells and cytokines/chemokines in meningiomas were selected and reviewed. Results: Monocytes were detected as the most abundant infiltrating immune cells in meningiomas. Only brain-invasive meningiomas elicited a monocytic response at the tumour–brain interface. The expression of cytokines/chemokines in meningiomas has been studied to some extent, and some of them form autocrine loops in the tumour cells. Paracrine interactions between tumour cells and glia cells have not been explored. Conclusion: It is unknown to what extent meningiomas elicit an immune response in the brain parenchyma. We speculate that tumour–brain crosstalk might only be relevant in cases of invasive meningiomas that disrupt the pial–glial basement membrane.

OBJECTIVE: Meningioma is the most common primary intracranial neoplasm. Only 1%–3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown. METHODS: The authors used a NanoString targeted gene expression panel with focus on 787 genes relevant in meningioma pathology and neuroinflammatory pathways to investigate patients with grade III meningiomas treated at Rigshospitalet from 2000 to 2020 (n = 51). A temporal dimension was added to the investigation by including samples from patients’ earlier grade I and II meningiomas and grade III recurrences (n = 139 meningiomas). The authors investigated changes in neuroinflammatory gene expression signatures in 1) grade I meningiomas that later transformed into grade III meningiomas, and 2) grade III meningiomas compared with nonrecurrent grade I meningiomas. RESULTS: The authors’ data indicate that FOXM1, TOP2A, BIRC5, and MYBL2 were enriched and the HOTAIR regulatory pathway was enriched in grade III meningiomas compared with nonrecurrent grade I meningiomas. They discovered a separation of malignant and benign meningiomas based only on genes involved in microglia regulation with enrichment of P2RY12 in grade I compared with grade III meningiomas. Interestingly, FOXM1 was upregulated in premalignant grade I meningioma years before the grade III transformation. CONCLUSIONS: The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.

Meningiomas are the most common intracranial tumor. During pregnancy, explosive growth of a known meningioma occasionally occurs, but the underlying reasons remain unknown. Prolactin has been suggested as a possible key contributor to pregnancy-related meningioma growth. This study sets out to investigate prolactin and prolactin receptor status in 29 patients with pregnancy-related meningiomas in Denmark, from January 1972 to December 2016, as compared to 68 controls aged 20–45 years, also undergoing resection of a meningioma. Furthermore, we investigated potential differences in the progesterone and estrogen receptor statuses, WHO grade, Ki-67 labeling indices, and locations of the resected meningiomas between the cases and controls. Immunohistochemical analyses were performed, and histopathology and intracranial location were assessed with the investigator blinded for the case–control status. None of the samples stained positive for prolactin and very few samples stained positive for prolactin receptors, equally distributed among cases and controls. Estrogen and progesterone receptors generally followed the same distributional pattern between groups, whereas above cut-point Ki-67 labeling indices for both groups were observed. In conclusion, our results did not support the notion of prolactin as a key contributor to pregnancy-related meningioma growth. Rather, the similarities between the cases and controls suggest that meningiomas early in life may comprise a distinct biological entity.