BACKGROUND: WHO grade 2 meningiomas, including atypical, chordoid, and clear cell subtypes, form a heterogenous group of meningiomas with varying aggressiveness and clinical behavior. OBJECTIVE: To demonstrate the differences of clinical-histopathological characteristics and long-term outcomes among these 3 subtypes. METHODS: A total of 609 consecutive patients diagnosed with WHO grade 2 meningiomas (543 atypical meningiomas [AMs], 36 chordoid meningiomas [CMs], and 30 clear cell meningiomas [CCMs]) from 2010 to 2018 were enrolled in this study. We compared the clinical-histopathological characteristics and long-term outcomes in these 3 subtypes and assessed survival differences among the subtypes. Targeted panel sequencing of meningioma-relevant genes was performed in the cases of CM. RESULTS: The patients with CCM were significantly younger than those with AM (P < .001) and CM (P = .016). CMs were more likely to receive gross total resection than AMs and CCMs (P = .033). The Ki-67 index was lower (P < .001) while the progesterone receptors-positive rate was higher (P = .034) in CM than in AM and CCM. Importantly, survival analysis demonstrated that CM had better progression-free survival (P = .022) and overall survival (P = .0056) than non-CM tumors. However, the PFS of CM was still worse than WHO grade 1 meningiomas (P < .001). Alterations in NF2 (20.6%) and KMT2C (26.5%) were associated with poorer PFS in CM (P = .013 for NF2; P = .021 for KMT2C). CONCLUSION: Patients with CM had better long-term postoperative outcomes than the other WHO grade 2 subtypes. A lower Ki-67 index, higher PR status, higher extent of resection, and lower frequency of NF2 alteration might contribute to favorable clinical outcomes of CM.

Meningioma is the most common intracranial tumor. Sometimes, meningiomas can develop malignant transformation (MT). In this review, we review the incidence of MT of meningiomas. The incidence of MT of grade 2 meningiomas is likely to be higher than benign meningiomas. Approximately 1% to 4% of WHO Grade 1 meningiomas may undergo MT, while about 26% to 33% of Grade 2 meningiomas experience MT. Time to MT of grade 2 meningiomas seemed to be shorter than MT of grade 1 meningiomas. The time for Grade I meningiomas to undergo MT is approximately 5 years, while Grade II meningiomas typically experience MT in about 3 years. Several risk factors may be associated with MT, including non-skull base location, high mitotic Index, a larger primary tumor size, shorter recurrence time interval and male. Potential molecular mechanisms of MT include chromosomal abnormalities (Chromosome 22q deletion, NF2 gene mutation, loss of chromosome 1p), genomic alterations (FOXM1, CDKN2A/B and TERTp), and meningioma cancer stem cells. Secondary meningiomas may have poor tumor control rates and overall survival rates than primary meningiomas. Besides, the role of radiotherapy in MT of meningiomas is unclear. Major concerns are whether radiotherapy can induce MT of meningiomas, and whether radiotherapy can prolong time to MT through long term control of meningiomas. This review summarizes the MT of meningiomas, and may provide the direction for further study of meningiomas.

Background: Adjuvant radiotherapy (RT) is one of the most commonly used treatments for de novo high-grade meningiomas (HGMs) after surgery, but genetic determinants of clinical benefit are poorly characterized.Objective: We describe efforts to integrate clinical genomics to discover predictive biomarkers that would inform adjuvant treatment decisions in de novo HGMs.Methods: We undertook a retrospective analysis of 37 patients with de novo HGMs following RT. Clinical hybrid capture-based sequencing assay covering 184 genes was performed in all cases. Associations between tumor clinical/genomic characteristics and RT response were assessed. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan–Meier method.Results: Among the 172 HGMs from a single institution, 42 cases (37 WHO grade 2 meningiomas and five WHO grade 3 meningiomas) were identified as de novo HGMs following RT. Only TERT mutations [62.5% C228T; 25% C250T; 12.5% copy number amplification (CN amp.)] were significantly associated with tumor progression after postoperative RT (adjusted p = 0.003). Potential different somatic interactions between TERT and other tested genes were not identified. Furthermore, TERT alterations (TERT-alt) were the predictor of tumor progression (Fisher’s exact tests, p = 0.003) and were associated with decreased PFS (log-rank test, p = 0.0114) in de novo HGMs after RT.Conclusion: Our findings suggest that TERT-alt is associated with tumor progression and poor outcome of newly diagnosed HGM patients after postoperative RT.

Meningioma represents the most common intracranial tumor in adults. However, it is rare in pediatric patients. We aimed to demonstrate the clinicopathological characteristics and long-term outcome of pediatric meningiomas (PMs). We enrolled 74 patients with intracranial PMs and analyzed their clinicopathological characteristics. Targeted next generation sequencing was used to detect alterations in meningioma relevant genes. Progression-free survival (PFS) was compared between PMs and adult meningiomas (AMs). Univariate and multivariate Cox analyses were employed to evaluate the predictive values of clinicopathological characteristics. A nomogram was constructed and its predictive accuracy evaluated. 40 females (54.1%) and 34 males (45.9%) patients, with the gender ratio of 1.18:1, were identified. 9 (12.2%) cases were clinically diagnosed as NF2-related Schwannomatosis (NF2-SWN), while 65 (87.8%) were sporadic. Ventricular location was found in 16 patients (21.6%). 19 patients (25.7%) experienced recurrence during a median follow-up period of 33 months (range 2 -145.25 months). The 3-, 5-, and 8-year PFS rates was 74.74%, 74.74%, and 59.38%, respectively. The PFS of the PM and AM cohorts were not significantly different, with or without propensity score matching. NF2 mutation was observed in 33 sporadic PMs (52.4%), whereas alterations in other genes (AKT1, TRAF7, SMO, PIK3CA, KLF4) frequently mutated in AMs, were not identified. The proportion of NF2 mutation in PMs was significantly lower in the skull base than other locations (p = 0.02). One anaplastic PM harbored TERT promoter mutation. Of note, in sporadic PMs, NF2 mutations were not significantly associated with PFS (p = 0.434) or overall survival (OS) (p = 0.60). The multivariate Cox analysis showed NF2-SWN (p < 0.001) and extent of resection (p = 0.013) to be independently associated with the PFS of PMs. Our prognostic model showed predictive accuracy for long-term PFS in PMs as the 3-, 5- and 8-year Area Under the Curve (AUC) was 0.927, 0.930, and 0.870, respectively. PM was characterized by its relative male predominance, ventricular location, NF2-SWN, and NF2 mutation. Of note, PMs had similar prognosis to AMs and NF2 alteration was not significantly associated with PFS in PMs.