H3 K27M Mutations in Thalamic Pilocytic Astrocytomas with Anaplasia.

BACKGROUND: The revised WHO classification of central nervous system tumors, published in 2016, has recognized the H3 K27M mutation as a critical genetic signature defining a new group of infiltrative astrocytomas designated "diffuse midline glioma, H3 K27M mutant". Although the majority of H3 K27M mutations arise in the setting of diffusely infiltrative tumors, there are rare reports of compact tumors with low-grade histologic features harboring this mutation. The prevalence and clinical significance of this mutation in pilocytic astrocytomas remain unclear.

CASE DESCRIPTION: We report two young adult patients with H3 K27M-mutated thalamic pilocytic astrocytomas who presented to medical attention with symptomatic hydrocephalus requiring urgent intervention. We present our experience with this unusual tumor and recommend a treatment paradigm of maximal safe surgical resection followed by chemotherapy and radiation.

CONCLUSIONS: Stereotactic biopsies may undergrade some adult thalamic pilocytic astrocytomas. Thus, we recommend that all of these tumors be evaluated for the H3 K27M mutation. Further, we believe that H3 K27M-mutant thalamic pilocytic astrocytomas require aggressive multi-modality treatment and that these treatments should be guided by the molecular findings, as opposed to the histologic ones.