Massive dissemination of adult glioblastomas.

Abstract

Recent autopsy data suggests a high incidence of leptomeningeal metastases (LM), Acta Neuropathologica 2014; 128: 573 and subventricular spread (SVS), Acta Neuropathologica 2014; 127: 605 in pediatric diffuse intrinsic pontine gliomas, but both LM and SVS also occur in adult glioblastoma (GBM). Autopsy is required to fully appreciate this tumor behavior. From January 1, 2014 to January 3, 2015 we conducted 239 adult autopsies, 8 of which were identified on search to be GBMs. Of these 8 GBMs, one-half showed bulky spread (SVS (n = 2), LM (n = 2), bone marrow (n = 1)), and 2 of these 4 additionally had microscopic LM. In patient 1 GBM with a very minor epithelioid component on the surgical specimen spread evolved to a predominantly epithelioid GBM (E-GBM) phenotype in the clinically-unsuspected LM at autopsy. Patient 2, with malignant glioma with primitive neuroectodermal tumor (MGPNET), had a secondary GBM with a noncanonical isocitrate dehydrogenase 1 (IDH1) mutation and 11-year-survival; autopsy showed encasement of the entire bilateral ventricular system by SVS. Patient 3, also with an IDH1- positive secondary GBM, had survived 10 years, only to develop thrombocytopenia and succumb to extensive bone marrow replacement by his tumor. Patient 4 had a radiation-induced posterior fossa GBM that demonstrated LM/SVS spread pattern identical to that described in pediatric diffuse pontine gliomas. Several subtypes of adult GBM (MG-PNET, posterior fossa GBMs, E-GBMs) have recently been recognized to have a propensity for LM; autopsy permission should especially be sought for these tumor types. Correlation between genetics and LM/SVS is now possible and may shed further light on this behavior.