Molekulare Eigenschaften von spinalen pilozytischen Astrozytomen: Eine multizentrische Analyse bei Erwachsenen

Adult spinal pilocytic astrocytomas (sPA) pose a challenge to clinicians primarily due to their rarity and limited understanding of their clinical progression and biology. Utilizing epigenetic methodologies and a large database of diffusely infiltrative intramedullary spinal cord gliomas (IMSCG), this study seeks to comprehensively characterize the clinical and molecular aspects of adult intramedullary pilocytic astrocytomas.

This study involves a retrospective analysis of patients who underwent surgery for diffusely infiltrating IMSCG at three university medical centers in Germany. Clinical data were retrieved from digital case records. To identify distinct molecular patterns and provide a diagnosis, we employed the 850K DNA methylation array, with subsequent classification using the Heidelberg classifier. T-distributed stochastic neighbor embedding (t-SNE) was used to identify clustering patterns. The study was approved by the ethics committee (PV4904).

Forty-six patients (n=46) were included in the analysis of IMSCG. Among them, 21 tumors were histologically identified as pilocytic astrocytomas (PA). Sixteen of these tumors (n=16) closely matched the molecular characteristics of PA. The average age at the time of surgery for the PA patients was 26.6 ± 16.4 years. Near gross total tumor debulking was achieved in 44% of sPA cases, while 22% of patients underwent biopsy, and the remaining 33% had subtotal resections, all without major complications. Postoperatively, 33% of sPA patients experienced a decline in McCormick scores, and only one patient required gait assistance. The methylation array identified a molecular match with a score of >0.7 in 25% of the sPA patients using the 11.4 classifier and in 44% of cases using the latest 12.8 classifier. Interestingly, in the t-SNE plot, the 16 sPA formed a distinct cluster adjacent to other PA without clear overlap with existing tumor sample clusters.

IMSCG present challenges in diagnosis when relying solely on their histological characteristics. Especially for sPA, a combined approach of using both epigenetic and histological analysis is recommended for accurate diagnosis. These sPA tumors may possess distinct epigenetic features that set them apart from their cerebral counterparts.