gms | German Medical Science

Objective: Intraventricular meningiomas (IVMs) are rare tumors which only account for 0.5–3% of all meningiomas (MGMs) and up to 14% of all intraventricular tumors. Although there is increasing knowledge about the clinical and molecular features of MGMs per se, little is known about this rare subtype. Hence, we were interested whether IVMs differ from MGMs in other locations and investigated our institutional series on a molecular level.

Methods: IVM tumor samples and corresponding clinical data of 22 consecutive cases were collected at our institution between 2000 and 2018. Tumors were profiled by targeted panel sequencing. The panel contained 130 genes reported to be frequently mutated in brain tumors including MGMs. Sequencing was done by applying a custom hybrid capture approach (Agilent Technologies, CA, USA) on a NextSeq500 instrument (Illumina). For single nucleotide variant calling, we used SAMtools mpileup, while for InDel calling Platypus was utilized. The panel was designed to assess the frequency of known mutations and was not designed to detect novel mutational events.

Results: In our series of 22 IVMs (n=20 WHO°I and n=2 WHO°II), age ranged from 14 to 75 years (median: 53 years). The female-to-male ratio was 1.75. Most tumors were located in the lateral ventricles (n=17, 77,3%), followed by III ventricle (n=4, 18,2%, and IV ventricle (n=1, 4,5%). The mean tumor size was 40 cm³ (range 0.8–134 cm³). Despite gross total resection, 4 IVMs (18%) relapsed (n=3 WHO°I, n=1 WHO°II) within the time frame of 3 to 324 months. In 18 tumors (n=17 patients; n=1 matching relapsed tumor), we were able to assess mutations or indels in frequently affected genes by panel sequencing. Stopgain mutations (n=3), splicing error (n=1) and frame shifts (n=2) in the NF2 gene were observed in 6 out of 17 patients (35%). However, non-NF2 tumors failed to show any of the mutations reported in convexity and skull base meningiomas including TRAF7, AKT1, SMO, KLF4, PIK3CA and TERT. Furthermore, comparison of NF2 vs. non-NF2 IVMs showed a trend towards higher Ki67 in the NF2 wildtype group (p=0.05) but did not differ in demographic or clinical characteristics.

Conclusion: In summary, non-NF2 tumors accounted for 65% of all IVMs in our series. They seem to differ in their aberration profile from other non-NF2 meningiomas due to the lack of known genetic alterations. Further investigation of other potential driver mutations genes is currently ongoing.