Diffuse Midline Glioma, H3 K27M-Mutant: A Case Report

• Published in: American journal of clinical pathology 2018-09, Vol.150 (suppl_1), p.S34-S34
• Main Authors: Leon, Jose Rodriguez, Berenguer, Juan Perez, Vargas, Bryan Morales, Roman, Keila Rivera, Prieto, Juan Vigo, Alvarez, Eduardo Labat, Torres, Luis Ferrer
• Format: Article
• Language: English
• Subjects: Astrocytoma; Brain tumors; Case reports; Central nervous system; Glial fibrillary acidic protein; Glioma; Headache; Hydrocephalus; Magnetic resonance imaging; Microvasculature; Mutants; Mutation; Nausea; Neurosurgery; Polymerase chain reaction; Thalamus; Tumors; Vomiting
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/aqy090.083

Abstract Purpose The updated 2016 World Health Organization Classification of Tumors of the Central Nervous System defines a novel category for diffuse midline gliomas with H3 K27M mutation. Previously, these tumors were included within diffuse gliomas, which are further classified and graded as diffuse astrocytomas, anaplastic astrocytomas, and glioblastomas. These diffuse gliomas are found more frequently in children and can be seen in midline structures. For diffuse midline gliomas in general, the finding of an H3 K27M mutation confers a worse prognosis than that of wild-type cases. Case Description We report the case of a diffuse midline glioma, H3 K27M mutant, in a 21-year-old female who presented with headaches, dizziness, nausea, and vomiting. Clinical Approach A brain MRI revealed a heterogeneously enhancing left thalamic lesion with mass effect and obstructive hydrocephalus. Clinical Findings After neurosurgical intervention and thorough histopathologic evaluation, the diagnosis of diffuse midline glioma, H3 K27M mutant, WHO grade IV was made. Histologically, the tumor was characterized by a diffuse astrocytic morphology without necrosis or microvascular proliferation. Immunohistochemically, the lesion was focally positive for glial fibrillary acidic protein (GFAP), had a 1% to 2% proliferative index by Ki-67, and was positive for antihistone 3.1/3.3 K27M mutation. Additionally, RT-PCR was negative for IDH1/IDH2 mutations (wild-type), and FISH analysis exhibited no codeletion changes in 1p/19q. Hypothesis This newly defined entity represents a critical diagnostic challenge for practicing surgical pathologists. The importance of recognizing this entity relates to the fact that even when the tumor is conventionally graded as grade II astrocytoma histologically, it behaves as a much more aggressive tumor if the H3 K27M mutation is identified. Regardless of the presence of anaplastic features, a diffuse midline glioma with H3 K27M mutation is classified as WHO grade IV. This case underlines the importance of molecular evaluation to correctly subtype gliomas due to its prognostic and clinical significance.