Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions.

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.

Percutaneous vertebroplasty as treatment of malignant vertebral lesions: a systematic review and GRADE evaluation resulting in a Danish national clinical guideline.

PURPOSE: To summarize the recommendations from the national clinical guideline published by the Danish Health Authority, regarding cemental augmentation as treatment for painful vertebral lesions, in patients with malignant disease. METHODS: A multidisciplinary working group formulated recommendations based on the GRADE approach. RESULTS: Two of the questions were based on randomized studies and one on professional consensus. The guideline recommends cemental augmentation for painful vertebral lesions in patients with malignant diagnosis, either hematological or non-hematological. Fracture of the posterior wall is not a contradiction to cemental augmentation, but care should always be taken while injecting the cement, to decrease the risk of cemental leaks into the spinal canal. CONCLUSION: The recommendations are based on low-to-moderate quality of evidence or professional consensus as well as patient preferences and positive and harmful effects of the intervention. The working group recommends more randomized studies on patients with different malignant diseases and painful vertebral lesions comparing percutaneous vertebroplasty/kyphoplasty and conservative treatment to confirm the conclusion in this guideline. These slides can be retrieved under Electronic Supplementary Material.