Diffuse Glioma, H3K27M-Mutant
Historically, the diagnosis of pediatric tumors of the central nervous system (CNS) has relied on histology and immunohistochemistry, with glial tumors staining with glial fibrillary acidic protein (GFAP) and embryonal tumors with neuronal markers like synaptophysin. The 2016 WHO classification of tumors of the CNS, for the first time, incorporated pathognomonic molecular features in the diagnosis of tumors and defined new tumor entities like diffuse glioma, H3 K27M-mutant. The immunohistochemistry with antibodies specific to the H3K27M mutation has a 100% sensitivity and 100% specificity, and is a highly reliable diagnostic tool for this disease entity.
We report the second case, in the literature, of a tumor staining diffusely positive for synaptophysin and being negative for GFAP, but harboring the mutant histone H3 p.K27M protein. This pathognomonic molecular finding established the diagnosis of a high-grade glioma, for a tumor that based on immunohistochemistry, resembled an embryonal tumor. High-grade glioma with H3 K27M-mutant is an aggressive tumor with median survival of 6 months. The incorporation of molecular features can augment histopathological evaluation in the diagnostic process, and in some instances even alter the diagnosis, with a significant impact on prognosis and treatment.
Contributed by Lincy Thomas, MD, Naina Gross, MD, Spencer Thompson, MD, Rene McNall-Knapp, MD, David Ellison, MD, PhD, Jason Chiang, MD, PhD, Jo Elle Peterson, MD, Kar-Ming Fung, MD, PhD , Abhishek Bavle, MBBS