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Intraventricular meningiomas (IVMs) are rare (0.5–5%) and usually low-grade (90% grade I) brain neoplasms. Their recurrence rate is lower than that of extra-axial meningiomas, but their surgical resection can be burdened with life-threatening complications, which represent the major cause of the reported 4% mortality. The aim of this study is to characterize the molecular portrait of IVMs to identify potential therapeutic targets. For this, we explored mutations and copy number variations (CNV) of 409 cancer-related genes and tumor mutational burden (TMB) of six cases, using next-generation sequencing. Five IVMs were grade I and one was grade II; none recurred, in spite of partial surgical resection in one case. NF2 mutation was the only recurring alteration and was present in three of the six IVMs, in association with SMARCB1 mutation in one case. None of the cases was hypermutated (TMB > 10 mutations/Mb). NF2-mutant progressing or recurring IVMs could potentially be treated with targeted therapies applied to other NF2-mutant tumors, as an alternative to surgery or radiosurgery, while in view of their low TMB they are unlikely candidates to immune check-point inhibition.

Abstract Giant cell glioblastoma (GC-GBM) is a rare variant of IDH-wt GBM histologically characterized by the presence of numerous multinucleated giant cells and molecularly considered a hybrid between IDH-wt and IDH-mutant GBM. The lack of an objective definition, specifying the percentage of giant cells required for this diagnosis, may account for the absence of a definite molecular profile of this variant. This study aimed to clarify the molecular landscape of GC-GBM, exploring the mutations and copy number variations of 458 cancer-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI) in 39 GBMs dichotomized into having 30–49% (15 cases) or ≥ 50% (24 cases) GCs. The type and prevalence of the genetic alterations in this series was not associated with the GCs content ( 10 mut/Mb, including two (5%) that harbored MSI and one with a POLE mutation. The frequency of RB1 and NF1 alterations and TMB counts were significantly higher compared to 567 IDH wild type (P

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR–based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.