LAUSR

Dear Editor, Genetic and epigenetic profiling of tumors via whole exome sequencing (WES) and methylation analysis has led to an improved understanding of the molecular and genetic causes of tumorigenesis, profoundly impacting how brain cancers are diagnosed and treated. We present the case of an 8-year-old boy, found to have a pontine lesion on brain MRI (Figure 1A). The tumor histomorphology was unusual, showing glial features and areas with a vaguely nested, perivascular pseudo-rosette pattern, but lacked abundant Rosenthal fibers and was not diagnostic for pilocytic astrocytoma (PA). Immunohistochemical staining revealed GFAP positive, synaptophysin negative, EMA negative cells with H3K27me3, INI1/BAF47 and ATRX nuclear expression retained (normal). Microvascular proliferation and pseudopalisading necrosis were not present (Figure 1B). Ki-67 proliferative index was up to 5% to 7%. IDH1/2 mutations and the BRAF/ KIAA1549 fusion, which is frequently present in posterior fossa PA, were absent. Based on these features, the tumor was initially favored to be a glioma. Independent review at two other institutions acknowledged difficulty classifying the tumor based on histomorphology and raised the possibility of an intracerebral schwannoma. Whole genome methylationbased clustering using “The Brain Tumor Methylation Classifier” assigned