BACKGROUND: Turcot syndrome (TS) is a rare genetic disorder of DNA mismatch 
repair predisposing to glioblastoma (GBM) in the type 1 variant.
OBJECTIVE: We report the clinicopathological and genetic features of 3 gliomas 
in TS type 1 patients.
METHODS: Three cases were reviewed from our clinical and pathology files at 
Washington University with the diagnosis of TS 1 and GBM over the past 14 years. 
All 3 had classic features of GBM, but also demonstrated bizarre multinucleated 
giant cells and remarkably high mitotic indices. Sarcomatous regions were found 
in 2. Despite these features, the patients had prolonged survival times of 44, 
55, and >29 months (ie, currently alive). Demographic and clinical courses were 
abstracted from retrospective chart review. Histopathology was reviewed from all 
cases and reticulin histochemistry was added to identify possible foci of 
sarcomatous differentiation.
RESULTS: All 3 had classic features of GBM, and Ki-67 labeling indices ranged 
from 18 to 45%. All 3 also showed strong nuclear p53 positivity. Two cases were 
negative for the isocitrate dehydrogenase 1 (IDH1) mutation, and O-Methylguanine 
methyltransferase promoter methylation was seen in one. Fluorescence in situ 
hybridization was done using 1p/1q, 19p/19q, centromere 7/epithelial growth 
factor receptor (EGFR), and PTEN/DMBT1 probes. Focal EGFR amplification was seen 
in one case, although other common alterations of either primary GBMs or gliomas 
with prolonged survival (1p/19q codeletion) were lacking.
CONCLUSION: We conclude that 1) the giant cell variant of GBM is overrepresented 
in TS; 2) gliosarcomas may also be encountered; and 3) survival is often 
favorable, despite histological anaplasia and exuberant proliferation.