A WHO grade IV diagnosis in the face of a low-grade histophenotype: a difficult situation for the surgical neuropathologist

This midbrain mass in a 33-year-old patient has low-grade histology (minimal mitoses, low MIB-1 cell cycling index, and a single Rosenthal fiber), yet it harbors the H3 K27M mutation. Perivascular lymphocytes were present, but ganglioglioma was ruled out. So, the following diagnosis was rendered: diffuse midline glioma, H3 K27M mutant, WHO grade IV.  Other molecular changes included loss of p16 (CDKN2a) and loss of PTEN and 10 centromere, consistent with monosomy for chromosome 10. The discordance between histopathology and molecular findings can make the diagnostician squeamish about rendering a high-grade diagnosis. But, sometimes, this is where we find ourselves.