CNS methylation classifiers may misclassify normal developing cerebellar cortex as medulloblastoma.

DNA methylation profiling is commonly utilized in tumor diagnosis and has shown diagnostic specificity in many contexts. We recently noted that several CNS tumor classifiers used for neuropathology clinical diagnostics fail to appropriately classify pediatric cerebellar cortex tissue as non-neoplastic. Our study illustrates a gap in classifier accuracy that is most evident with samples from very young patients (<6 months). In this setting,classifiers typically assign medulloblastoma, SHH-activated, and occasionally show high-confidence scores. Neuropathologists practicing in pediatric settings should be aware of the histologic appearance of immature cerebellar tissue, and exercise caution when performing methylation profiling of samples of uncertain neoplastic status for patients in early infancy. DNA methylation array was performed using Infinium MethylationEPIC v1.0 and/or v2.0 on postmortem cerebellar cortex samples ranging from premature (28 gestational weeks) to postnatal 10 days and 4 months of age.