PATH-18. SHOULD LEPTOMENINGEAL DISSEMINATION (LMD) AT DIAGNOSIS WITH AN H3K27M MUTATION BE ENOUGH TO BE CONSIDERED A DIFFUSE MIDLINE GLIOMA (DMG) H3K27M ALTERED?

Abstract

Abstract Currently diffuse midline glioma (DMG) H3K27M-altered is defined as a diffuse, infiltrating midline glioma with an altered H3K27M pathway. A number of brain tumors have been reported with alterations in H3K27M that do not meet DMG diagnostic criteria and the clinical significance of H3K27M alteration in these tumors is unknown. Patients with extensive leptomeningeal disease often do not undergo large tumor resections and as a result there is limited tissue available for histologic evaluation. We present two patients who presented with leptomeningeal disease (LMD) and given extent of disease were only able to undergo subtotal resection. In both of these cases, the pathology specimens were found to have H3K27M alterations by immunohistochemistry but did not meet the diagnostic criteria for DMG due to the lack of histologic evidence of infiltration. Both patients were young women (age 23 and 28) who presented with new headaches, nausea, and vomiting and were found to have extensive LMD. Both were treated initially with proton craniospinal radiation and concurrent temozolomide. Within 1 year of initial diagnosis, both had radiographic and clinical progression of both parenchymal and LMD. Despite aggressive treatment, both patients clinically declined and transitioned to hospice within 2 years of diagnosis. Our understanding of the H3K27M altered pathway at this time is limited, and the significance of this mutation is unknown in tumors where an infiltrating component is not captured histologically. While LMD is rare at initial presentation of DMG, it is seen commonly at disease progression. We propose that the presence of H3K27M alteration with known leptomeningeal disease at diagnosis should be considered grade 4 histology and DMG for the purposes of prognostication and clinical trial consideration. Given ability to detect this mutation in CSF sampling, this may spare patients from surgical intervention and expedite time to treatment.