Massive dissemination of adult glioblastomas

Abstract

Background: 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.

Methods: From January 1, 2014 to January 3, 2015 we conducted 239 adult autopsies, 8 of which were identified on search to be GBMs.

Results: 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.

Conclusions: 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.